The Role of Mild Hyperbaric Therapy in Autism - Curando el Autismo

curandoelautismo.com

The Role of Mild Hyperbaric Therapy in Autism - Curando el Autismo

The Role of Mild Hyperbaric

Therapy in Autism

Julie A. Buckley, MD, FAAP

Curando El Autismo

Puerto Rico

1 April, 2012


Objectives

The Role of MHBT in Autism

• Review the fundamental concept of autism as a

whole body medical illness

• Review what hyperbaric therapy is and how

oxygen impacts the human body

• Reviewing the medical literature on the impact of

hyperbaric oxygen on the problems we see in

autism

• Discuss the implementation of this therapy.


Autism- A Whole Body Medical Disease

1. Social skills problems

2. Immune dysregulation

1. Communication problems

2. Inflammatory bowel disease

3. Toxicants

3. Chronic inflammatory response

1. Behavior problems

2. Methylation chemistry problems

3. Oxidative stress


Autism- A Treatable Disease

1. Socialization

Just Like Any Other!

2. Balance immune system

3. Antiinflammatories

1. Communication

2. Manage the gut

3. Detoxify

1. Behavior

2. Enhance methylation

3. Anti-oxidants


Getting Our Children Back-

In Search of the Silver Bullet

Manage the gut disease

Manage the immune dysregulation

Manage the inflammation

Manage the oxidative stress

Plus

Improve mitochondrial function

Help the parents too!


HBOT Definition

Hyperbaric oxygen therapy (HBOT) involves

inhaling increased levels of oxygen (up to

100% oxygen) at greater than 1 atmosphere

(atm) in a pressurized chamber.


Alexander the Great (320 BC)


Fontaine (1877)


Draeger Chamber (1917)


Cunningham (1928):

“Monstrous Hyperbaric Chamber”


Dead Sea

1.05 atm

1.0 atm

0.3 atm

Air Pressure at

Different Elevations


Basic Physiology of Oxygen Transport

AMBIENT AIR

Alveolar air

Pulmonary capillaries

Venous blood

Heart

Systemic arterial blood

Capillaries

Interstitial and intercellular fluid

THE CELL: perioxome, endoplasmic reticulum, mitochondria


Oxygen at Regular Atmospheric Pressure

• Travels attached to

red blood cells

• Four molecules of

Oxygen per red

blood cell

• Oxygen only

crosses a short

distance into tissue

when it arrives at its

destination


Henry’s Law- Defines What Happens With

Hyperbaric Pressure

The amount of any gas that will dissolve in a liquid at a given

temperature is a function of the partial pressure of the gas in

contact with the liquid and the solubility coefficient of the gas

in that particular liquid.

• Simplified: As the pressure of any gas increases, more of that

gas will dissolve into any solution with which it is in free

contact.

VG = aPg

VL


Henry’s Law in Real Life


Oxygen-Under Pressure Dissolves Into Plasma

• Much more oxygen

travels to the tissue

• Different laws of

physics apply because

the oxygen is floating

freely, not bound

• When it arrives at

tissue it floods into

the damaged area,

penetrating much

further

•This speeds healing


Oxygen Washes Into Tissue…

At atmospheric pressure, it

washes into tissue a short way

At hyperbaric pressure, it floods

tissue, penetrating deeply


Hyperbarics for Neurologic Problems

• Initial research looking at how to use

hyperbarics as a medical tool used higher

pressure

• Brain doesn’t do well with higher pressure

• As clinicians use lower pressure and find good

results, research is beginning to look at lower

pressure

• Studies are very promising!


Edited by J. H. Zhang. Flagstaff, AZ Best Publishing Company


Courtesy Dan Rossignol, MD

Scholey et al., 1999 Physiol Behav 67(5): 783-9


Oxygen administration selectively enhances

cognitive performance in healthy young

adults: a placebo-controlled double-blind

crossover study.

Moss et al., 1998 Psychopharm 138:27-33

• Double-blind, placebo-controlled, cross-over

design in 20 healthy young adults.

• Attention, reaction time, and picture

recognition reaction time were all significantly

improved.


Hyperbarics in Autism

• First step has been clinical observation-

observing response one patient at a time-

what we see is overwhelmingly positive

• Second steps are research- many different

sorts of trials, of different sizes and types.

• Some will be very positive, others less so

• MOST IMPORTANT: Evidence based medicine

includes clinical observation and experience!


Rossignol and Rossignol, 2006 Med Hypotheses 67(2):216-28


• Six children, ages 2-7

HBOT Case Series

• 1.3 atm and 28% oxygen for 40 sessions

• Scores calculated pre- and post-treatment for:

Autism Treatment Evaluation Checklist (ATEC)

– Childhood Autism Rating Scale (CARS)

– Social Responsiveness Scale (SRS)

Rossignol and Rossignol, 2006 Med Hypotheses 67(2):216-28


Predominantly a safety-study

Rossignol et al., 2007 BMC Pediatrics 7:36


Pilot Study Summary

• HBOT at both 1.5 atm/100% oxygen (6 children) and 1.3

atm/24% oxygen (12 children) led to subjective clinical

improvements in children with autism and was safe/well

tolerated

• HBOT at both pressures decreased an inflammatory

marker (CRP, pooled p=0.021)

• HBOT at both pressures did not appreciably worsen

oxidative stress markers (as measured by changes in

plasma oxidized glutathione, p=ns)


CONCLUSION: Children with autism who received

hyperbaric treatment at 1.3 atm and 24% oxygen for

40 hourly sessions had significant improvements in

overall functioning, receptive language, social

interaction, eye contact, and sensory/cognitive

awareness compared to children who received slightly

pressurized room air.

Rossignol et al., 2009 BMC Pediatr 9:21


We sought to determine whether HBOT leads to parental

reported behavioral changes and alterations in cytokines in

children with ASD. Ten children completed 80 sessions of

HBOT and all improved by 2 points on the clinician-rated CGI-I

scale (much improved) as well as several parent-completed

measures of behavior. The lack of a control group limits the

ability to determine if improvements were related to HBOT.

Enrolled children did not exhibit abnormal cytokine levels at

baseline and no significant changes in mean cytokine levels

were observed.

Bent et al., 2011 J Autism Dev Disord, in press


What, and/or Why, is MHBT

Helpful in Autism?


Some Autism Findings

• Autistic children compared to neurotypical

controls have:

– Relative Cerebral Hypoperfusion- Role of MHBT

– Evidence of Inflammation

• Neuroinflammation

• GI inflammation and dysbiosis

– Immune Dysregulation

– Increased Oxidative Stress

– Relative Mitochondrial Dysfunction


SPECT Scanner

Shows regional blood flow and brain FUNCTION


Differences Between Scan Types

CT and MRI: Show Anatomy SPECT: Shows Function


Neurologic Impact-

…altered perfusion in the medial prefrontal

cortex and anterior cingulate gyrus, …

altered perfusion in the right medial

temporal lobe. The perfusion abnormalities

seem to be related to the cognitive

dysfunction observed in autism...


* Used with the permission of Dr. Kinaci


Cerebral Hypoperfusion

• Retrospective review of 108 children with autism who received 50

1-hour/day HBOT sessions at 1.5 atm/100% oxygen

• All patients had temporal lobe hypoperfusion on SPECT and normal

brain MRI

• Perfusion increased in the temporal lobes in 82%, frontal lobes in

85%, and other brain areas in 76%

* Used with the permission of Dr. Kinaci


SPECT Scan Changes with HBT

Pre MHBT

Post 40 hours 1.3 ATA


SPECT Scan Changes with HBT

Pre Treatment MHBT Post Treatment 40 hrs 1.3 ATA


Some Autism Findings

• Autistic children compared to neurotypical controls

have:

– Relative Cerebral Hypoperfusion

– Evidence of Inflammation- Role of MHBT

• Neuroinflammation

• GI inflammation and dysbiosis

– Immune Dysregulation

– Increased Oxidative Stress

– Relative Mitochondrial Dysfunction

– Serotonin Abnormalities


Neuroinflammation in Autism


Neuroinflammation in Autism

Cross section of

cerebellum of

autistic child.

Activated

microglial cells

take up the red

dye


Neuroinflammation in Autism


HBT in Neuroinflammation

Benson RM, Minter LM, Osborne BA, Granowitz EV. Clin Exp Immunol. 2003

Oct;134(1):57-62.

Hyperbaric oxygen inhibits stimulus-induced proinflammatory

cytokine synthesis by human blood-derived monocytemacrophages.

Hyperoxia alone and pressure alone did not affect cytokine

production.

In summary, HBO exposure transiently suppresses stimulusinduced

proinflammatory cytokine production and steady

state RNA levels.


GI Inflammation in Autism

Normal Colonoscopy

Lymphonodular

Hyperplasia


GI Inflammation in Autism

Normal Esophagus

Courtesy Arthur Krigsman

Eosinophilic Esophagitis

Courtesy Arthur Krigsman


GI Inflammation in Autism-

Bile Reflux Esophagitis

Courtesty Arthur Krigsman


GI Inflammation in Autism-

Small Bowel Aphthous Ulcerations

Pill Cam photos

courtesy Arthur

Krigsman


Vicious Cycles- Gut Disorders in Autism-

Small Bowel Erosive Ulcerations

(with enteric protein loss)

Pill Cam photos

courtesty Art

Krigsman


Harrison et al., 1994 Adv Exp Med Biol 345:789-96


Al-Waili et al., 2006 Scientific World Journal 6:425-41


Wilson et al., 2006 Brain Res 1098:126-8


HBT and GI Issues

Reflux, Colitis, Obstruction

• Koloskow and Dumurov (1986): working with rat

ulcers, 60% healed with HBOT

• Komarov et al (1985) reported 127/132 pts

confirmed healing by endoscopy with 10-15

treatments at 2 ATA.

• Efuni et al (1986) 217 pts with peptic ulcer disease

and HBOT 9-17 treatments at 2 ATA. 96% of PUD

were healed in 19 days which, when compared to

350 controls, represented a shortened duration of

illness by 7-28 days


HBT and GI Issues

Reflux, Colitis, Obstruction

• Chronic Idiopathic Intestinal Pseudo-

Obstruction: Case reported by Yokota et al

(2000) demonstrated complete relief of

obstruction and rapid decrease of abnormally

accumulated intestinal gas


HBT and GI Issues

Reflux, Colitis, Obstruction

• Undersea Hyperb Med. 2002 Winter;29(4 )

Hyperbaric oxygen improves healing in

experimental rat colitis.


Dysbiosis in Autism- evidence in urine


Dysbiosis in Autism- evidence in stool


Dysbiosis in Autism

These studies demonstrate significant

alterations in the upper and lower

intestinal flora of children with lateonset

autism and may provide insights

into the nature of this disorder.”

Finegold et al., 2002 Clin Infect Dis 35(Suppl 1):S6–16


Effect of MHBT on Bacteria

“Suppression of

infection by moderate

hyperoxia is comparable

with that reported by

Burke after timely,

adequate doses of typespecific

antibiotics.”


Effect of MHBT on Dysbiosis

Bile Duct

Ligation

Bile Duct

Ligation

Akin et al., 2001 Dig Dis Sci 46(8):1657-62

“…hyperbaric

oxygen

treatment can

prevent both

bacterial

overgrowth

and

translocation

effectively.”


Some Autism Findings

• Autistic children compared to neurotypical controls

have:

– Relative Cerebral Hypoperfusion

– Evidence of Inflammation- Role of MHBT

• Neuroinflammation

• GI inflammation and dysbiosis

– Immune Dysregulation- Role of MHBT

– Increased Oxidative Stress

– Relative Mitochondrial Dysfunction- Role of MHBT

– Serotonin Abnormalities


Evidence of Immune Dysregulation in

Autism

J Neuroimmunol. 172:198-205, March 2006

“Children with ASD had increased activation of both Th1 and

Th2 arms of the adaptive immune response, with a Th2

predominance, and without the compensatory increase in the

regulatory cytokine IL-10.”

DYSREGULATION !


Evidence of Immune Dysregulation in

Autism

“Our data suggest that a potential side effect

of vaccination with live attenuated viruses

may be an increase in the expression of IgE.”


Evidence of Immune Dysregulation in

Autism


Role of MHBT in Immune Regulation

“We concluded that the immunomodulatory

effect of hyperbaric oxygen contains a

component for which hyperpressure is sufficient

and a component that apart from

hyperpressure also requires hyperoxygenation.”


Role of MHBT in Immune Regulation


Effects of HBOT on Immune Dysregulation in Autism

Marker Autism Finding HBOT Effect

IL-10

HSP-90

[Ashwood and Anthony,

2004]

(due to increased antibodies

to HSP-90) [Evers, 2002]

[Buras, 2006]

[Thom, 2002]

Lymphocytic activity [Stubbs, 1977] [Lee, 1993]

T-helper cells [Warren, 1986] [Nyland, 1989]

Serum IgA [Gupta, 1996] [Nyland, 1989]

Serum IgE

Courtesy Dan Rossignol, MD

[Lucarelli, 1995; Gupta,

1996]

[Olszanski, 1992]


Some Autism Findings

• Autistic children compared to neurotypical controls

have:

– Relative Cerebral Hypoperfusion

– Evidence of Inflammation- Role of MHBT

• Neuroinflammation

• GI inflammation and dysbiosis

– Immune Dysregulation

– Increased Oxidative Stress

– Relative Mitochondrial Dysfunction- Role of MHBT

– Serotonin Abnormalities


James SJ 2004. Am J Clin Nutr. 80,1611–17.

Total glutathione

levels were 46%

lower and

oxidized

glutathione was

72% higher in

autistic children

compared to

typical controls.


Oxidative Stress and HBOT

• Oxidative stress is caused by an imbalance of

oxidants and antioxidants

• At pressures below 2.0 ATA, there is good evidence

that HBOT can decrease oxidative stress by

increasing the activity of anti-oxidant enzymes such

as SOD, catalase, glutathione peroxidase, hemeoxygenase-1,

and by reducing lipid peroxidation

• At pressures above 2.5 ATA, the literature is

conflicted. Some studies show that HBOT may still

decrease oxidative stress; others show an increase in

oxidative stress


Role of MHBT in Reducing Oxidative Stress


Role of HBOT in Reducing Oxidative Stress

“…exposure to HBO

induces an

antioxidant defense

mechanism(s) that is

responsible for

retarding the

development or

accelerating the

regression of

atherosclerotic

lesions”

Kudchodkar et al., 2000

Arterioscler Thromb Vasc

Biol 20:1637-43


Effects of HBOT on

Measures of Oxidative Stress in Autism

Measure Classification Autism Finding HBOT effect

Glutathione peroxidase Antioxidant Enzyme [Yorbik, 2002] [Gulec, 2004]

Superoxide dismutase Antioxidant Enzyme [Yorbik, 2002] [Gulec, 2004; Gregorevic,

2001; Ozden, 2004]

Heme-oxygenase 1 Antioxidant Enzyme ? [Speit, 2000; Rothfuss,

2001; Rothfuss, 2002]

Catalase Antioxidant Enzyme [Zoroglu, 2004] [Nie, 2006]

Paraoxonase Antioxidant Enzyme;

Organophosphate

Detoxification

HSP-70 Cellular Protection Against

Oxidative Stress

Malondialdehyde Marker of Oxidative Stress

and Lipid Peroxidation

[D’Amelio, 2005; Pasca,

2006]

[Sharifi, 2004]

[Purcell, 2001] [Dennog, 1999; Shyu,

2004]

[Chauhan, 2004] [Gulec, 2004; Ozden, 2004]

Ceruloplasmin Antioxidant [Chauhan, 2004] [Moak, 1984]

Glutathione Antioxidant [James, 2004] [Ozden, 2004]

Zinc Antioxidant [Yorbik, 2004] [Ozden, 2004]

Copper Metal [Adams, 2004] [Ozden, 2004]

Courtesy Dan Rossignol, MD


Some Autism Findings

• Autistic children compared to neurotypical controls

have:

– Relative Cerebral Hypoperfusion

– Evidence of Inflammation- Role of MHBT

• Neuroinflammation

• GI inflammation and dysbiosis

– Immune Dysregulation

– Increased Oxidative Stress

– Relative Mitochondrial Dysfunction- Role of MHBT

– Serotonin Abnormalities


Role of MHBT in Mitochondrial Genesis

Gutsaeva et al., 2006 Neuroscience 137:493-504

“…O 2 activates regional

mitochondrial DNA

transcription, replication,

and mitochondrial

biogenesis in the

hippocampus”


Mitochondrial Genesis with HBOT

Gutsaeva et al., 2006

Neuroscience 137: 493-504


A Side Effect for Parents!!!

• We accompany our children into the chamber

• Many of us have poorly controlled stress

• Many of us are being diagnosed with posttraumatic

stress disorder, anxiety, depression,

etc.

There is new research- conducted on combat

veterans- showing that MHBT is helpful


Significant Improvements:

• Neurological Exam

• IQ (increased 14 points)

• Delayed memory

• Working memory

• Impulsivity

• PTSD symptoms

• Depression

• Anxiety

• Quality of Life


Dysbiosis

Immune

Dysregulation

Courtesy Dan Rossignol, MD

Cerebral

Hypoperfusion

AUTISM

Mitochondrial

Dysfunction

Neuroinflammation

and GI inflammation

Oxidative

Stress


Dysbiosis

Immune

Dysregulation

Courtesy Dan Rossignol, MD

Cerebral

Hypoperfusion

MHBT

Mitochondrial

Dysfunction

Neuroinflammation

and GI inflammation

Oxidative

Stress

More magazines by this user
Similar magazines