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© 2004-2017 Millennium Lectures “Bringing clinical science to you.”“Bringing clinical science to you.”
A Grouped Knowledge...
June 2016
50% greater suicide
rate in military than in
the civilian population!!
Where science is being used there is Hope!
What is the PTSD Concept?
 PTSD (post-traumatic stress disorder) is a mental
health problem that some people develop afte...
Then what is TBI?
 The Dept. of Veteran Affairs and the DoD define TBI
as a “traumatically induced structural injury and/...
6
Figure 7.0: There are common elements in the symptomatology associated with
TBI and PTSD which can account for confusion...
There is an inverse relationship between the level of inflammation and
the level of neurosteroids as there is an inverse r...
Combat Trauma Syndrome (CTS) takes into
account all the significant and “insignificant”
traumas that an individual is expo...
 Standard training and
operations
 Repetitive Gun fire
 Flash Bang
 Improvised Explosive
Device (IED)
 Controlled ent...
The 10 Top Symptoms associated with mildTBI:CTS
1. Fatigue ( 100% of patients )
2. Diminished libido.
3. Disturbed sleep p...
 Mood changes (Emotionally Labile).
 Changes in social behavior.
 Changes in personality.
 Diminished Executive Functi...
 Increased aggressive behavior.
 Loss of Short term memory.
 Decreasing long term memory.
 Abnormal Libido and Sexual ...
 Problems with reading (Alexia).
 Difficulty with doing mathematics.
 Inability to focus visual attention.
 Difficulti...
 Production of hallucinations.
 Visual illusions - inaccurately seeing objects.
 Defects in vision (Visual Field Cuts)....
 Department of Defense data revealed that
from 2000–2011, 339,046 service members
were diagnosed with a mTBI.
 This was ...
 We are realizing that a large number of Iraq and
Afghanistan veterans are returning with diagnoses of
PTSD.
 This is ba...
1. Trauma to the body or directly to the skull can
induce neurotrauma.
2. Neurotrauma has two components:
1. Tissue damage...
Molecular changes occur that are not visible on CT, MRI, HDTI, or MEG.
DepressionBi-PolarParanoiaAnger
Neuroinflammation and Psychiatric Illness. Journal of Neuroinflammation
2013, 10:43. Souhel Najjar, Daniel M Pearlman2, Ke...
 An increase in oxidative stress leads to
inflammation, which in turn stimulates microglia to
release chemicals that caus...
Inflammation after Trauma: Microglial Activation and
Traumatic Brain Injury. ANN NEUROL 2011;. Anil F. Ramlackhansingh, MR...
Oxidative Stressors
• Reactive Oxygen
• Reactive Nitrogen
• Lipid Peroxidase
Inflammation
• TH1
• Cytokines
• Chemokines
D...
Early intervention
to control
inflammation will
promote a more
neuro-permissive
environment
fostering recovery.
25The Inf...
4. Physical damage to the brain affects the production
of hormonal signaling between the Hypothalamus
and the Pituitary le...
Traumatic Brain Injury-Related Hypopituitarism: A
Review and Recommendations for Screening Combat
Veterans. MILITARY MEDIC...
Hypopituitarism Secondary to Head Trauma. The Journal of Clinical Endocrinology &
Metabolism, 2000, 85(4), S. Benvenga, et...
Acute
3 mo
◄Recovery►
Chronic
12 mo
Hormone Deficient 56% 36%
Gonadotropic 32% 21%
Corticotropic 19% 9%
Somatotropic 9% 10...
31
A Boolean logic search of Google Scholar using “Hormone-X and Depression”
yielded the above results. These were not scr...
 Open enrollment of 200 Veterans and Active Military
with a history of CTS.
 Pre-requisites: Blast Trauma, labeled PTSD,...
 Millennium Blast Trauma Panel 3624
 Standard biochemical assessment.
 Based upon clinical symptoms and the
biochemical...
35
Hormone Groupings Composition
Growth Factor GH, IGF-1, IGFBP-3
Testosterone and related Free and Total Testosterone DHEA-s...
Pituitary dysfunction after traumatic brain injury. Sorin G. Beca, Brent
Masel, and Randall J. Urban. Traumatic Brain Inju...
 The “normal reference” and “reference ranges” are not
representative of the individual, but of the group used to establi...
1. Neuroinflammation and
2. Restoring the Neurosteroid balance
to optimal physiological levels.
3. Concurrently removing a...
 Oral treatment consisting of 80-90% Nutraceuticals
or supplements that address inflammation.
 N-Acetyl Cysteine (NAC)
...
Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury.
Katharine Eakin, et al. Dept of Neurosurgery, Case Western Reserv...
Modulation of inflammation in brain: a matter of fat. Akhlaq A.
Farooqui, et al. Departments of Molecular and Cellular Bioc...
No.
#
Mean
Age
Program
Time
History of
Suicide
Medication
Status (%off)
Median
Improvement
57m/1f 39.8 415 Days 2 attempts...
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
Popula...
Year Cost Includes
1st
$5000.00 – $6,500.00 All labs, supplements, and consults.
2nd
$3,500.00 - $4,500.00 All labs, suppl...
The End Q &
A
Hormones that modulate inflammation
Growth Hormone Vitamin D3 IGF-1
Allopregnanolone Pregnenolone Progesterone
Testosteron...
Characterization of interface Astroglial scarring in the human brain
after blast exposure: a post-mortem case series. The ...
The Millennium-Warrior Angels Foundation 3 year TBI study
The Millennium-Warrior Angels Foundation 3 year TBI study
The Millennium-Warrior Angels Foundation 3 year TBI study
The Millennium-Warrior Angels Foundation 3 year TBI study
The Millennium-Warrior Angels Foundation 3 year TBI study
The Millennium-Warrior Angels Foundation 3 year TBI study
The Millennium-Warrior Angels Foundation 3 year TBI study
The Millennium-Warrior Angels Foundation 3 year TBI study
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The Millennium-Warrior Angels Foundation 3 year TBI study

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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.

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The Millennium-Warrior Angels Foundation 3 year TBI study

  1. 1. © 2004-2017 Millennium Lectures “Bringing clinical science to you.”“Bringing clinical science to you.” A Grouped Knowledge Presentation Study Results: 2014-2016 EDUCATE TRAIN TREAT TRACK
  2. 2. June 2016 50% greater suicide rate in military than in the civilian population!!
  3. 3. Where science is being used there is Hope!
  4. 4. 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 sexual assault.
  5. 5. 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.”
  6. 6. 6 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 Continuum of untreated TBI.
  7. 7. 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. 7 - -
  8. 8. 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.
  9. 9.  Standard training and operations  Repetitive Gun fire  Flash Bang  Improvised Explosive Device (IED)  Controlled entry blasts  Mortar fire  Falling down  Artillery fire  Carl Gustav/LAW  Motor Vehicle Accident  Motorcycle Accident  Blunt Head Trauma  Falling or jumping from roof top(s).  Parachute jumps  Hand to hand training 10
  10. 10. 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 Neuroinflammation causing Brain Hormone dysregulation.
  11. 11.  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). 12
  12. 12.  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. 13
  13. 13.  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. 14
  14. 14.  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. 15
  15. 15.  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 June 2013
  16. 16.  We are realizing that a large number of Iraq and Afghanistan veterans are returning with diagnoses of PTSD.  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
  17. 17. 1. Trauma to the body or directly to the skull can induce neurotrauma. 2. Neurotrauma has two components: 1. Tissue damage, and 2. Neuro-Inflammation 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.
  18. 18. Molecular changes occur that are not visible on CT, MRI, HDTI, or MEG. DepressionBi-PolarParanoiaAnger
  19. 19. 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  Bipolar Disorder  Obsessive Compulsive Disorder  Schizophrenia
  20. 20.  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
  21. 21. 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 regions.  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. 23
  22. 22. Oxidative Stressors • Reactive Oxygen • Reactive Nitrogen • Lipid Peroxidase Inflammation • TH1 • Cytokines • Chemokines Disruption of BBB • Hypoxia • Ischemia • Cerebral Edema Excitotoxicity • Glutamate • Calcium Mitochondrial Dysfunction BAX ► AIF, CytoC. Cell Death • Necrosis • Apoptosis • Cavitation • Loss of Brain Traumatic Brain Injury: Oxidative Stress and Neuroprotection. Antioxidants & Redox Signaling Vol. 00, N0. 00, 2013. Carolin Cornelius, Vittorio Calabrese, et al. Disruption of Receptors • NMDA, Sigma=1 • GABA-α and -β • AMPA Neurosteroids • Deficiencies • Enzyme Inhibition • Retarded production
  23. 23. Early intervention to control inflammation will promote a more neuro-permissive environment fostering recovery. 25The Infamous Inflammatory component
  24. 24. 4. Physical damage to the brain affects the production of hormonal signaling between the Hypothalamus and the Pituitary leading to disruption of the homeostatic mechanisms. 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.
  25. 25. 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 USA  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.
  26. 26. 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 Stalk Resection Normal Infarct of Anterior Pituitary Hemmorage of Post. Pituitary Hemmorage of Hypothalamus Other Anatomic Lesions of the Pituitary, Stalk, and Hypothalamus at CT/MRI Post-Head Trauma Hypopituitarism (PHTH). 8 28 26 24 N 4 2 93%
  27. 27. Acute 3 mo ◄Recovery► Chronic 12 mo Hormone Deficient 56% 36% Gonadotropic 32% 21% Corticotropic 19% 9% Somatotropic 9% 10% ↑ Thyrotrophic 8% 3% 30 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? 
  28. 28. 31 A Boolean logic search of Google Scholar using “Hormone-X and Depression” yielded the above results. These were not screened for accuracy. 128,000 157,000 85,600 398,000 23,000 590,000
  29. 29.  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. Selection Criteria
  30. 30.  Millennium Blast Trauma Panel 3624  Standard biochemical assessment.  Based upon clinical symptoms and the biochemical and hormonal testing, an individualized treatment protocol was developed. Protocol
  31. 31. 35
  32. 32. 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
  33. 33. 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 37 These are tangible, objective, and measurable levels of hormones. , DHEA-s , ▲ Insulin , LH (Aka Death) Another Paradigm Shift is in the interpretation of the lab results.
  34. 34.  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. 38 10 9015 We maintain all our neurosteroids at their optimal median level and never above high-normal levels. We always stay physiological. 50
  35. 35. 1. Neuroinflammation and 2. Restoring the Neurosteroid balance to optimal physiological levels. 3. Concurrently removing all psychotropic agents.
  36. 36.  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)  Quercetin
  37. 37. 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.
  38. 38. 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 thromboxanes.  Down-regulation of NfKappaB.  Not pharmaceutical intervention but Nutraceutical intervention.
  39. 39. No. # Mean Age Program Time History of Suicide Medication Status (%off) Median Improvement 57m/1f 39.8 415 Days 2 attempts 90% 73% Ranges 23-77 YRS 125-1069 Days 1- 6x 4-16 meds 10% - 100% No. Clomid (CPC) Testosterone (TPC) Combination (CPC+TPC) 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% improvement in 90 days.
  40. 40. 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
  41. 41. Year Cost Includes 1st $5000.00 – $6,500.00 All labs, supplements, and consults. 2nd $3,500.00 - $4,500.00 All labs, supplements, and consults. 3rd $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. Millennium Protocols
  42. 42. The End Q & A
  43. 43. Hormones that modulate inflammation Growth Hormone Vitamin D3 IGF-1 Allopregnanolone Pregnenolone Progesterone Testosterone Estradiol Cortisol
  44. 44. 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 Controls Astroglial Scarring blocks nerve regeneration. GFAP=glial fibrillary acidic protein GFAP

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