The Millennium-Warrior Angels Foundation 3 year TBI study. This is the definitive lecture on what constitutes a TBI, how to identify and treat it, supported with our evidence on more than 200 documented cases.
I would like to start by getting some conventional concepts out on the table…
Then there is the DOVA and DOD who have defined TBI as a “traumatically induced structural injury and/or physiological disruption of brain function as a result of an external force.”
The confusion that exists is in the understanding of which precedes which. Does PTS precede TBI or is it the other way around? My frequently offensive view is that TBI has happened in 99% of the cases and precedes the progressive development of the symptoms we have erroneously referred to as PTS. If you are dealing with a patient that comes to you with PTS or PTSD, then you know someone missed an opportunity to diagnose and treat the underlying physiological disruption of brain function secondary to one or more traumatic brain injuries.
There is an inverse relationship between the level of inflammation and the levels of hormones as there is an inverse relationship between neurosteroid levels and symptomatology.
There is an inverse relationship between the level of inflammation and the levels of hormones as there is an inverse relationship between neurosteroid levels and symptomatology.
So for the past 13 years we at the Millennium have been working on a project that started to look at the defining parameters for TBI and PTSD. In 2009, we turned our attention to our heroes in the military and those on any given Sunday. We subsequently decided to move our efforts into the Active and Retired military communities. In so doing we decided on a new label for these individuals and came up with the term Combat Trauma Syndrome. This presentation covers or work with the military from 2014-2015-2016.
So what is CTS, many of the cases that we have seen are of Men who served and were told they did not have a TBI because they did not have Glasgow scores less than 15, which is considered normal or the number that anyone sitting in this room would be given at this moment. It is because of this rigid interpretation that has allowed those who have truly had a traumatic brain injury to be pe3received as a psychiatric case months or even years after the injury.
This is a list of some of the most common precipitators for the development and progression of CTS with some being ignored as causative factors.
And here are the most common symptoms that can develop immediately or days, weeks, or months after a mild TBI.
Then when we start breaking it down into regions of the brain that are traumatized we see patterns of neurocognitive and neurobehavioral changes along with functional deprivation.
Read 1: We have assumes that there is a unique LINE that has to be crossed before one is considered to have sustained a TBI. No longer is it required to be knocked down, made unconscious or put into a coma in order to acquire the hall-mark symptoms associated with TBI or PTS. Although more subtle TBIs can delelope symptoms weeks, months, or years later. Read 2: It turns out that, in light of the physical damage to brain tissue (called the Phase I Injury), the secondary wave of unseen damage precipitated by inflammation is the real culprit in the neurobehavioral and cognitive impairments that develops subsequent to the trauma (the Phase II Injury). This is the all too common; Silent or Stealth disease that is being talked about with very little being done about it. Read 3: The physical trauma initiates the release of chemistry that begets the inflammation that alters the physiology in and around neurons. Neuronal function is altered creating mood disorders, depression, anxiety, suicidal ideation, bi-polar personalities, autism, schizophrenia, and loss of libido. Both the physical and chemical connections between neurons and therefore areas of the brain are disrupted. Martellus Bennett Shines As Blocker For Patriots In Rob Gronkowski's
Hypopituitarism Secondary to Head Trauma. J. Clinical Endocrinology and Metabolism 85:1353-1361. Benvenga S, et al. 2000. The use of CT/MRI to identify the distribution of lesions occurring after TBI only helps to support the premise that the ultimate etiology behind hormonal dysfunction, after neurotrauma, originates not from the Anterior or Posterior pituitary but, from the hypothalamus. The acceptance of this data, which has been presented by a number of researchers, would allow us to reformulate the validity of not only the value of standard challenge testing but the need for acute hormonal intervention in order to enhance repair and rehabilitation from the trauma. Without acknowledging this pattern of trauma we will continue to test and treat in the same manner as before missing the opportunity to make a significant difference in the potential outcome to the patient’s quality of life. MLG2011
Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury. Eur J Endocrinol. 2006; 154(2):259-65 (ISSN: 0804-4643). Schneider HJ; Schneider M; Saller B; Petersenn S; Uhr M; Husemann B; von Rosen F; Stalla GK. Max Planck Institute of Psychiatry, Clinical Neuroendocrinology Group Kraepelinstr. 10, 80804 Munich, Germany. OBJECTIVE: Cross-sectional studies report a high prevalence of hypopituitarism after traumatic brain injury (TBI); however, no longitudinal studies on time of manifestation and reversibility exist. This study was conducted to assess hypopituitarism 3 and 12 months after TBI. DESIGN: This was a prospective, longitudinal, diagnostic study. METHODS: Seventy-eight patients (52 men, 26 women, mean age 36.0 years) with TBI grades I-III and 38 healthy subjects (25 men, 13 women, mean age 36.4 years) as a control group for the GHRH + arginine test were studied. The prevalence of hypopituitarism was assessed 3 and 12 months after TBI by GHRH + arginine test, short adrenocorticotropic hormone (ACTH) test, and basal hormone measurements in patients. RESULTS: After 3 months, 56% of all patients had impairments of at least one pituitary axis with axes being affected as follows: gonadotropic 32%, corticotropic 19%, somatotropic 9% and thyrotropic 8%. After 12 months, fewer patients were affected, but in some cases new impairments occurred; 36% still had impairments. The axes were affected as follows after 12 months: gonadotropic 21%, somatotropic 10%, corticotropic 9% and thyrotropic 3%. CONCLUSIONS: Hypopituitarism occurs often in the post-acute phase after TBI and may normalize later, but may also develop after the post-acute phase of TBI.
Now that we know what central and peripheral hormones to look at the issue becomes in how to interpret the results into meaningful and positive outcomes under treatment.
Pituitary dysfunction after traumatic brain injury. Sorin G. Beca, Brent Masel, and Randall J. Urban. Traumatic Brain Injury Rehabilitation, Treatment, and Case Management, Third Edition CRC Press 2010
Then there is the issue of how to interpret the lab results that we are using to make the diagnosis of Inflammatory brain disease. If we continue to use the mythical reference ranges we will miss the opportunity to treat these patients. Our goal is not to have levels that are just inside the range but at levels that we are seeing as being therapeutic. Not base3d upon the numerical results from some lab test but by the improvement in the patients condition. And, what we are finding is that the levels are an individualized issue. There is no One Size Fits All solution.
Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury. Katharine Eakin, et al. Dept of Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, Ohio, Dept of Anatomy and Anthropology, Sackler School of Medicine, Tel-Aviv University, Dept of Otolaryngology, Neurobiology, Communication Sciences and Disorders, and Bioengineering, University of Pittsburgh, Pennsylvania, Dept of Otolaryngology, Spatial Orientation Center, Naval Medical Center San Diego, San Diego, California, Graduate Program in Neuroregeneration, Taipei Medical University, Taipei City, Taiwan
Modulation of inﬂammation in brain: a matter of fat. Akhlaq A. Farooqui, et al. Departments of Molecular and Cellular Biochemistry, and Entomology, The Ohio State University, Columbus, Ohio, USA.
Characterization of interface astroglial scarring in the human brain after blast exposure: a post-mortem case series. The Lancet Neurology, 06, 2016: 15:9, 944-953. 2016. Sharon Baughman Shively, Iren Horkayne-Szakaly, Robert V Jones, James P Kelly, Regina C Armstrong, Daniel P Perl. 2016
The Millennium-Warrior Angels Foundation 3 year TBI study
What is the PTSD Concept?
PTSD (post-traumatic stress disorder) is a mental
health problem that some people develop after
experiencing or witnessing a life-threatening event,
like combat, a natural disaster, a car accident, or
Then what is TBI?
The Dept. of Veteran Affairs and the DoD define TBI
as a “traumatically induced structural injury and/or
physiological disruption of brain function as a
result of an external force.”
Figure 7.0: There are common elements in the symptomatology associated with
TBI and PTSD which can account for confusion in making the most accurate
diagnosis. We look at PTSD as a 100% psychologically reactive condition that
does not have the physical component that differentiates it from TBI.
PTS is a
There is an inverse relationship between the level of inflammation and
the level of neurosteroids as there is an inverse relationship between
neurosteroid and symptomatology.
Combat Trauma Syndrome (CTS) takes into
account all the significant and “insignificant”
traumas that an individual is exposed to in the
course of their (military) life.
You don’t need to be knocked unconscious or even
knocked down to initiate the “silent” but
progressive brain damage (neuroinflammation) that
can take days or years to elicit symptoms that are
always classified as Psychiatric.
Standard training and
Repetitive Gun fire
Controlled entry blasts
Motor Vehicle Accident
Blunt Head Trauma
Falling or jumping from roof
Hand to hand training
The 10 Top Symptoms associated with mildTBI:CTS
1. Fatigue ( 100% of patients )
2. Diminished libido.
3. Disturbed sleep patterns. Insomnia.
4. Inattention with difficulty concentrating
5. Impaired memory, faulty judgment, slowed thinking.
6. Depression w/wo Anxiety and Panic Attacks.
7. Irritability with emotional outbursts of Anger.
8. Difficulty switching between two tasks.
9. Alcohol Abuse w/wo Drugs (self-medicating)
10. Increased infections, illnesses, and loss of muscle tone. 11
All associated with
Mood changes (Emotionally Labile).
Changes in social behavior.
Changes in personality.
Diminished Executive Functions.
Difficulty with problem solving.
Loss of flexibility in thinking.
Inability to sequence complex movements.
Loss of spontaneity in interacting with others.
Persistence of a single thought (Perseveration).
Inability to focus on task (Attending).
Inability to express language (Broca's Aphasia).
Increased aggressive behavior.
Loss of Short term memory.
Decreasing long term memory.
Abnormal Libido and Sexual Behavior.
Difficulty in understanding spoken words.
Difficulty with verbal ID of objects.
Difficulty in recognizing faces (Prosopagnosia).
Inability to categorize objects (Categorization).
Right lobe damage can cause persistent talking.
Problems with reading (Alexia).
Difficulty with doing mathematics.
Inability to focus visual attention.
Difficulties with eye and hand coordination.
Inability to locate the words for writing.
Inability to name an object.
Inability to attend to more than one object at a time.
Difficulty with drawing objects.
Difficulty in distinguishing left from right.
Lack of self awareness and/or surrounding space that leads to
difficulties in self-care.
Production of hallucinations.
Visual illusions - inaccurately seeing objects.
Defects in vision (Visual Field Cuts).
Difficulties with reading and writing.
Difficulty with locating objects in environment.
Difficulty with identifying colors (Color Agnosia).
Word blindness - inability to recognize words.
Difficulty in recognizing drawn objects.
Inability to recognize the movement of object.
Department of Defense data revealed that
from 2000–2011, 339,046 service members
were diagnosed with a mTBI.
This was 4.2% of the 5,603,720 who served in
the Army, Air Force, Navy and Marine Corps.
Report to Congress on TBI in the USA:
Understanding the Public Health Problem among Current and Former Military Personnel
We are realizing that a large number of Iraq and
Afghanistan veterans are returning with diagnoses of
This is based upon the growing number of visits to
the VA for psychosocial behavioral issues.
Studies estimate that at least 20-33% of returning
veterans have symptoms of PTSD (mTBI).
The Nation. April 16, 2013
1. Trauma to the body or directly to the skull can
2. Neurotrauma has two components:
1. Tissue damage, and
3. The combination of tissue damage and
inflammation causes an alteration in the molecular
biochemistry of the brain which alters the
physiology of neuronal functioning.
Molecular changes occur that are not visible on CT, MRI, HDTI, or MEG.
Neuroinflammation and Psychiatric Illness. Journal of Neuroinflammation
2013, 10:43. Souhel Najjar, Daniel M Pearlman2, Kenneth Alper, Amanda Najjar and Orrin Devinsky. Dept.
of Neurology, NY University School of Medicine, New York, NY 10016, USA
More recently, Neuro-Inflammatory and
immunological abnormalities have been documented
in patients with Classical Psychiatric Disorders.
Major Depressive Disorder
General Anxiety Disorders
Obsessive Compulsive Disorder
An increase in oxidative stress leads to
inflammation, which in turn stimulates microglia to
release chemicals that causes damage and
destruction to neurons and neuro-connections
within the brain (neuro-receptors).
A growing body of evidence suggests that many
psychiatric disorders, MDD, bipolar disorder (BD),
schizophrenia, and autism are associated with
distinct inflammatory mechanisms in the CNS.
The Role of Inflammation and Microglial Activation in the
Pathophysiology of Psychiatric Disorders. G. R. FRIES, et al., Neuroscience.
2015 Aug 6;300:141-54. Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The
University of Texas Medical School at Houston, Houston, TX, USA
Inflammation after Trauma: Microglial Activation and
Traumatic Brain Injury. ANN NEUROL 2011;. Anil F. Ramlackhansingh, MRCP, David J.Brooks,
MD,DSc, Richard J. Greenwood, FRCP, MD,and David J. Sharp, MRCP, PhD. Et al Centre for Neuroscience, Dept of Medicine,
Imperial College London, Hammersmith Hospital Campus, London, UK; Institute of Neurology, University College London, UK;
MRC Clinical Sciences Centre, Imperial College London, UK; and Neurodis Foundation , CERMEP Imagerie du Vivant, Lyon, France
Increased microglial activation can be present up to
17 years after TBI.
This suggests that TBI triggers a chronic
inflammatory response particularly in subcortical
This highlights the importance of considering the
response to TBI as evolving over time and suggests
interventions may be beneficial for longer intervals
after trauma than previously assumed.
promote a more
25The Infamous Inflammatory component
4. Physical damage to the brain affects the production
of hormonal signaling between the Hypothalamus
and the Pituitary leading to disruption of the
5. Additionally, inflammation alters the brain’s ability
to produce its own hormones; the Neurosteroids
which are made in Glia.
6. The loss of peripheral hormones and the central
Neurosteroids are at the foundation for loss of
cognition and induction of aberrant neurobehavior.
Traumatic Brain Injury-Related Hypopituitarism: A
Review and Recommendations for Screening Combat
Veterans. MILITARY MEDICINE, 175, 8:574, 2010. CPT(P) Arthur F. Guerrero , MC USA ; MAJ Abel Alfonso , MC
Recent civilian data obtained in those sustaining
head injuries, has found a High Prevalence of
Pituitary Dysfunction. Currently (2010), there is no
data available in the military population.
The authors found that the prevalence of anterior
hypopituitarism secondary to TBI was as high as 30–
80% after 24–36 months.
Hypopituitarism Secondary to Head Trauma. The Journal of Clinical Endocrinology &
Metabolism, 2000, 85(4), S. Benvenga, et al. Cattedra e Divisione di Endocrinologia, University of Messina School of
Medicine, 98125 Messina, Italy
0 5 10 15 20 25 30
Infarct of Posterior Pituitary
Infarct of Anterior Pituitary
Hemmorage of Post. Pituitary
Hemmorage of Hypothalamus
Anatomic Lesions of the Pituitary, Stalk, and Hypothalamus at
Post-Head Trauma Hypopituitarism (PHTH).
Hormone Deficient 56% 36%
Gonadotropic 32% 21%
Corticotropic 19% 9%
Somatotropic 9% 10% ↑
Thyrotrophic 8% 3%
Prevalence of anterior pituitary insufficiency 3 and 12
months after traumatic brain injury. Europe J Endocrinology. 2006; 154(2):259-
65. Schneider HJ; et al. GK. Max Planck Institute of Psychiatry, Clinical Neuroendocrinology Group Kraepelinstr. 10,
80804 Munich, Germany.
SO, how long after a blast trauma does it
take to have your hormones tested?
A Boolean logic search of Google Scholar using “Hormone-X and Depression”
yielded the above results. These were not screened for accuracy.
Open enrollment of 200 Veterans and Active Military
with a history of CTS.
Pre-requisites: Blast Trauma, labeled PTSD,
Polypharmacy, multiple suicide attempts, and
treatment resistance depression.
Positive Millennium-Mood Assessment.
Millennium Blast Trauma Panel 3624
Standard biochemical assessment.
Based upon clinical symptoms and the
biochemical and hormonal testing, an
individualized treatment protocol was
Hormone Groupings Composition
Growth Factor GH, IGF-1, IGFBP-3
Testosterone and related Free and Total Testosterone DHEA-s,
Estrogens and related Estradiol, Estrone, Pregnenolone, Progesterone
Thyroid Group TSH, Free T4 and T3, reverse T3, TSH Index
Cortisol Group ACTH and Cortisol (morning)
Ancillary Group LH, Prolactin, Insulin, Vitamin D, Insulin.
Inflammatory Markers: IL-6, IL-1β and TNF-α
All needed for a complete and comprehensive evaluation and treatment
Pituitary dysfunction after traumatic brain injury. Sorin G. Beca, Brent
Masel, and Randall J. Urban. Traumatic Brain Injury Rehabilitation, Treatment, and Case Management, Third
Edition CRC Press 2010
These are tangible, objective, and measurable levels of hormones.
, ▲ Insulin
Another Paradigm Shift is in the interpretation of the lab results.
The “normal reference” and “reference ranges” are not
representative of the individual, but of the group used to establish
these ranges (not part of the sample group).
So, we use the Gender Median as the target level which has always
lead to improvement of the individual, notably more than using the
“within the range” philosophy.
We maintain all our neurosteroids at their optimal median level and never
above high-normal levels. We always stay physiological.
1. Neuroinflammation and
2. Restoring the Neurosteroid balance
to optimal physiological levels.
3. Concurrently removing all
Oral treatment consisting of 80-90% Nutraceuticals
or supplements that address inflammation.
N-Acetyl Cysteine (NAC)
Tocopherols (Vitamin E = alpha, delta, gamma)
Omega-3/6 (Fish Oils = DHA/EPA)
Alpha Lipoic Acid (ALA)
Pyrroloquinoline Quinone (PQQ like CoQ-10)
Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury.
Katharine Eakin, et al. Dept of Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, Ohio,
Dept of Anatomy and Anthropology, Sackler School of Medicine, Tel-Aviv University, Dept of Otolaryngology,
Neurobiology, Communication Sciences and Disorders, and Bioengineering, University of Pittsburgh, Pennsylvania, Dept
of Otolaryngology, Spatial Orientation Center, Naval Medical Center San Diego, San Diego, California, Graduate Program
in Neuroregeneration, Taipei Medical University, Taipei City, Taiwan
We recently conducted, in an active theatre of war, a
study demonstrating that NAC has beneficial effects
on the severity and resolution of auditory, vestibular
and cognitive function sequelae after blast induced
mild TBI (mTBI) in military personnel.
Works through decreasing oxidative stress, free
radicals, and inflammation.
Modulation of inﬂammation in brain: a matter of fat. Akhlaq A.
Farooqui, et al. Departments of Molecular and Cellular Biochemistry, and Entomology, The Ohio State University,
Columbus, Ohio, USA.
Vitamin E, Omega-3 (Fish Oils) and NAC inhibit the
generation of prostaglandins, leukotrienes, and
Down-regulation of NfKappaB.
Not pharmaceutical intervention but Nutraceutical
57m/1f 39.8 415 Days 2 attempts 90% 73%
Ranges 23-77 YRS 125-1069 Days 1- 6x 4-16 meds 10% - 100%
57/1 47 11 3
58 military individuals, 57 males and 1 female, a variety of traumas(TBI), with
and without PTS, all on multiple medications, multiple suicide attempts, and
disrupted socialization. Average of treatment time 415 days (13.5mos), 90%
off medication with a 73% improvement in overall condition.
91% had a 50%
in 90 days.
Data: % Improvement & Ages
Distribution - Percent Improvement
10% 20 30 40 50 60 70 80 90 100%
4 1 0 0 6 7 13 8 9 9
Population by Age
20s 30s 40s 50s 60s 70s
6 29 13 5 3 2
91% with a 50% or greater response.
Age Group to Percent Improvement
Age 20-29 30-39 40-49 50-59 60-69 70-79
% 77.5 73.8 69.2 67.0 80.0 57.5
Year Cost Includes
$5000.00 – $6,500.00 All labs, supplements, and consults.
$3,500.00 - $4,500.00 All labs, supplements, and consults.
$2,500.00 - $3,500.00 All labs, supplements, and consults.
The Congressional Budget Office (CBO) reported in 2012
that the average Veteran is getting about $16,000.00 in
medical care – medication expenses per year. These are
the meds that keep an operator off the field preventing
them from doing what they were trained to do. Consider
the cost to train an operative/asset.
Characterization of interface Astroglial scarring in the human brain
after blast exposure: a post-mortem case series. The Lancet Neurology, 06, 2016: 15:9,
944-953. 2016. Sharon Baughman Shively, Iren Horkayne-Szakaly, Robert V Jones, James P Kelly, Regina C Armstrong,
Daniel P Perl. 2016
Astroglial Scarring blocks nerve regeneration.
GFAP=glial fibrillary acidic protein