Autism Hyper- Baric Oxygen Therapy and Dan Rossignol, M.D. DAN! Physician Clinical Assistant...
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Transcript of Autism Hyper- Baric Oxygen Therapy and Dan Rossignol, M.D. DAN! Physician Clinical Assistant...
AutismAutismHyper-Hyper-BaricBaricOxygenOxygenTherapyTherapy
andand
Dan Rossignol, M.D.Dan Rossignol, M.D.DAN! PhysicianDAN! Physician
Clinical Assistant ProfessorClinical Assistant ProfessorUniversity of VirginiaUniversity of Virginia
Department of Family MedicineDepartment of Family Medicine
Outline• Rise in autism prevalence• Effects of HBOT• Recent autism findings:
– Cerebral Hypoperfusion and HBOT– Neuroinflammation and GI Inflammation and HBOT– Increased excretion of porphyrins and HBOT– Oxidative Stress and HBOT
• HBOT safety• HBOT dosing• HBOT case series
Prevalence of Autism
• According to the U.S. Dept. Developmental Services, the prevalence of autism spectrum disorders increased 556% from 1991 to 1997.
• Autism is now more common than childhood cancer, Down’s syndrome, spina bifida or cystic fibrosis.
• 1 in 80 boys have autism (boys are affected 4 times as often as girls).
• 1 out of 68 families will have a child with autism.• Autism is increasing by 3.8% per year worldwide.
Prevalence of Autism
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HBOT Definition
• Hyperbaric oxygen therapy (HBOT) involves inhaling 100% oxygen at greater than 1 atmosphere absolute (ATA) in a pressurized chamber. (Feldmeier, Undersea and Hyperbaric Medical Society, 2003)
HBOT Approved Indications
• Air or gas embolism• Carbon Monoxide
Poisoning• Gas gangrene• Crush injuries and
compartment syndrome
• Decompression sickness
• Wound healing
• Severe anemia• Intracranial abscess• Necrotizing soft tissue
infections• Refractory
osteomyelitis• Skin flaps and grafts• Delayed radiation
injury• Thermal burns
The use of HBOT for autism is “off-label”
Postischemic BBB permeability
Veltkamp et al., 2005Postischemic cerebral edema
Rats 3 ATA100% oxygen
Effectsof HBOT
“Off-label” Studied Uses of HBOT• Cerebral Palsy (Montgomery, 1999)
• Amyotrophic Lateral Sclerosis (Steele, 2004)
• Complex Regional Pain Syndrome (Kiralp, 2004)
• Fetal Alcohol Syndrome (Stoller, 2005)
• Ischemic Brain Injury (Neubauer, 1992; Neubauer, 1998)
• Traumatic Midbrain Syndrome (Holbach, 1974)
• Closed Head Injury (Rockswold, 1992)
• Lupus (Wallace, 1996)
• Stroke (Nighoghossian, 1995)
• Myocardial Infarction (Shandling, 1997)
Recent Autism Findings
• Autistic children compared to neurotypical controls have:– Relative cerebral hypoperfusion– Evidence of neuroinflammation– Increased excretion of porphyrins– Increased oxidative stress
Bruneau et al., 1992Middle Cerebral Arteries
Abnormal Vascular Response: Abnormal Vascular Response: Cerebral Hypoperfusion
Wilcox, 2002
Hypoperfusion of the prefrontal and left temporal areas worsened and became “quite profound” as the age of the autistic child increased.
Cerebral Hypoperfusion inAutistics Correlated Clinically with:
– Repetitive, self-stimulatory, and unusual behaviors including resistance to changes in routine and environment (Starkstein, 2000)
– “Obsessive desire for sameness” and “impairments in communication and social interaction” (Ohnishi, 2000)
– Impairments in processing facial expressions and emotions (Critchley, 2000)
– Trouble recognizing familiar faces (Pierce, 2004) – Decreased language development (Wilcox, 2002) and
auditory processing (Boddaert, 2004)
– Decreased IQ (Hashimoto, 2000)
Temporal
WernickeBrodmann
Thalamus
TemporalAmygdala
Diseases in which inflammation causes decreased cerebral blood
flow• Sjögren’s syndrome (Lass, 2001)
• Behçet’s disease (Caca 2004)
• Viral encephalitis (Wakamoto, 2000; Nishikawa 2000)
• Kawasaki disease (Ichiyama, 1998)
• Lupus (Huang, 2002; Postiglione, 1998)
Inflammation: Cerebral Hypoperfusion
Mulligan et al., 2004
ReactiveAstroglia(green)
Vargas et al., 2005
Abnormal Astrocyte Vascular Control:Abnormal Astrocyte Vascular Control: Cerebral Hypoperfusion
HBOT and Cerebral Hypoperfusion
• HBOT has been used with success clinically in some hypoperfusion syndromes:
Fetal alcohol syndrome (Stoller, 2005)
Cerebral Palsy (Montgomery, 1999; Collet, 2001)
Closed head injury (Rockswold, 1992)
Stroke (Nighoghossian, 1995)
Heuser, 2002
SPECT Scans in a 4 year old autistic child after 10 sessions of HBOT at 1.3 atm and 24% oxygen
A – Normal control cerebellum B – Autistic brain with lossof Purkinje cell layer (P) andgranular cell layer (G)
Vargas et al., 2005
P
G
Autism and Neuroinflammation
HBOT and Inflammation
• Inflammation in Autistic Children– Multiple studies reveal that autistic individuals
have evidence of neuroinflammation and gastrointestinal inflammation
– In several studies, HBOT has been shown to have potent anti-inflammatory effects (Akin, 2002; Luongo, 1998; Sumen, 2001)
Saline
Diclofenac10 mg/kg
HBOT and Diclofenac10 mg/kg
HBOT Diclofenac20 mg/kg
HBOT and Diclofenac20 mg/kg
Sumen et al., 2001
INF
LA
MM
AT
ION
Room Air 160 mmHg
Lung Capillaries 100 mmHg
Leaving Heart 85 mmHg
Peripheral Arterioles 70 mmHg
Organ Capillaries 50 mmHg
Cells 1-10 mmHg
Mitochondria 0.5 mmHg(0.3% of inhaled oxygen)
Mitochondria is the final site of
heme production
Atmospheric Pressure of Oxygen
Autism and Oxidative Stress
Total glutathione levels were 46% lower and oxidized glutathione was 72% higher in autistic children compared to typical controls.
James, 2004
Antioxidants, HBOTand Oxidative Stress
• α-lipoic acid (Alleva, 2005)
• N-acetylcysteine (Yu, 2005; Pelaia, 1995)
• Vitamin E (Hollis, 1992)
• Riboflavin (Boadi, 1991)
• Selenium (Hollis, 1992; Boadi, 1991)
• Glutathione (Weber, 1990)
• Melatonin (Pablos, 1997)
Rats 4 ATA100% oxygen
HippocampusCerebral Cortex
Hypothalamus Cerebellum
HBOT and Oxidative Stress
Melatonin
HBOT and Stem Cells
In humans, HBOT at 2.0 ATA and 100% oxygen for 2 hours per treatment for 20 treatments doubled the number of circulating stem cells
Thom et al.in press
CerebralHypoperfusion
OxidativeStress
NeurodegenerativeDisease
AUTISMAUTISM
Summary
Neuroinflammationand GI inflammation
Excretionof Porphyrins
CerebralHypoperfusion
OxidativeStress
NeurodegenerativeDisease
Summary
Neuroinflammationand GI inflammation
HBOTHBOT StemCells
Excretionof Porphyrins
HBOT Safety at 1.3 ATA
• 111 children; 54 received HBOT at 1.3 atm and 40 treatments over 2 months:– 12 children had problems with their ears– No other safety issues noted
Collet et al., 2001
Side effects of HBOT
• Barotrauma (2%)
• Sinus squeeze
• Serous otitis
• Claustrophobia
• Reversible myopia
• Seizures (0.01 – 0.03%)