Hyperbaric Oxygen Therapy (HBOT) in Fetal Alcohol Spectrum Disorder (FASD)

Motherisk Int J 2020;1:5

Gideon Koren (1,2) Ornie Sachs MA (1)

Ariel University (1),  Motherisk Program, Shamir Hospital (2) and Sackler School of Medicine(3), Israel

Address for Correspondence:
Gideon Koren MD FRCPC FACMT
Ariel University, Ariel 40700 Israel
972587194777
gidiup_2000@yahoo.com

 

Abstract:

Question:

I am working in a center for children with Fetal Alcohol Spectrum Disorder. I have heard that hyperbaric chamber treatment may improve these children’s neurobehavioral achievements. Is this true?

Answer:

Preliminary results suggest that hyperbaric oxygen therapy can improve cognition and behaviors in children with Fetal Aocohol Spectrum Disorder with documented improvement in brain blood perfusion and oxygenation,

 

Fetal Alcohol Spectrum Disorder (FASD) describes the wide range of adverse physical, behavioural and cognitive effects resulting from ethanol exposure during embryonic and fetal development. The syndrome, described first by Lemoine in France in 1967 (1) was subsequently reaffirmed in 1973 by Jones and Smith in Seattle (2).

Understanding the mechanisms leading to FASD is critical in developing strategies for interventions. Over the last 50 years, numerous mechanisms have been proposed and tested experimentally. Goodlett and Horn have reviewed over 80 proposed mechanisms for FASD (3); however, to date very few interventional studies, either in animals or in humans have followed  the mechanistic framework presented by Goodlett and Horn.

Presently children afflicted by FASD are treated symptomatically for ADHD and different forms of disruptive behavior (4).

Hyperbaric oxygen therapy for FASD

In 2005 Stoller described cognitive improvement in a 15 year old boy with FASD after undergoing 40 HBOT treatments, followed 7 months later by an additional 33 treatments, each consisting of 60 minutes of low pressure therapy. At a six month follow up the boy maintained his gains in verbal memory, and improvement in impulsive behavior (4).  The mechanisms by which HBOT might improve cognitive function in FASD have not been studied by Stoller.

Hyperbaric oxygen therapy (HBOT) is a method of delivering extra oxygen through increased air pressure (5).The FDA has approved HBOT for decompression sickness, gas embolism, carbon monoxide and cyanide poisoning, skin grafts and flaps and thermal burns (5). In recent years the medical community has been striving to examine HBOT for a variety of additional indications however the proof of effectiveness of HBOT in these indications has to await further studies (5).

Motherisk first case of HBOT for FASD in 2017 involved a 15 year old girl who was adopted at 5 months of age from a home for deserted children in the former Soviet Union (6). At the time of adoption she exhibited malnutrition and severe developmental delay. Throughout her childhood she experienced severe learning disability, attention deficit, hyperactivity and impulsivity responding well to methylphenidate.   At 14 years of age she was diagnosed with FASD, based on  history of heavy maternal drinking, normal facial features and severe and complex neurocognitive and behavioral deficits.

A brain MRI, conducted prior to commencing the HBOT, showed normal anatomy. Prior to starting the HBOT, her achievements on standard neurocognitive tests showed impaired  memory ,  attention, impulsivity, executive function and verbal performance.

After 60 plus 40 additional treatments, each consisting of 60 minutes of low pressure therapy, she showed marked improvement in  verbal abilities (naming ability) and speed of processing information and the cognitive improvement affected daily functioning. She became able to plan her daily schedule and to better relate to people around her. She showed improved ability to read and write, both of which were very grossly delayed prior to HBOT.

Brain single proton emission computed tomographic brain imaging (SPECT) was performed prior to HBOT and after completion of the treatment series. .

 

SPECT imaging prior to HBOT showed areas of hypo- perfusion as follows: bilateral orbitofrontal, bilateral medial aspect of temporal lobes and right dorsolateral - frontal , as well the medial aspect of the left cerebellum .

Following the two sets of HBOT treatments, there was a marked improvement in perfusion to the left cerebellum as well as the right frontal lobe. The other areas of hypo perfusion were not improved. Overall, there was an increase in the functional volume of the brain from 1126 to 1188 ml.

A follow up with the girl and her parents 2 years after completion of the HBOT revealed that the HBOT was associated with clear and sustained improvement in attention, understanding mathematical concepts, in writing comprehension of text, with less grammatical errors.

The effect on impulsivity is described to have weaned off over time. There is still heightened stress and restlessness especially where she is demanded to maximize her abilities.

 

 

A Paradigm Shift in Approaching and Treating FASD

Over the last 50 years, FASD was regarded mostly as a form of static encephalopathy, where numerous neuronal functions have been permanently destroyed, explaining the inability of the brain to recuperate (4). Recent studies have provided convincing evidence that high oxygen can induce cerebral plasticity that lead to repair of chronic impairment of brain functions. The evidence has come mostly from controlled studies in patients with traumatic brain injury and prolonged post- concussion syndrome, even when HBOT started years after the trauma (7). This is important in the case of FASD, where brain insult occurred  in utero, and where one may tend to think that oxygen therapy may be too late for improvement. The documented restoration of  neuronal activity in alcohol- deranged and dysfunctional brain areas indicate that that HBOT delivers to the brain sufficient oxygen to activate neuroplasticity and restore impaired function many of us assumed have ceased to exist.

Alcohol insult to different brain functions, as shown by Goodlett and Horn for FASD, can impair microvascular integrity and reduce perfusion,  leading to impairment in numerous domains, including metabolism, neuronal activity, leading to loss of synapses and neuronal connectivity. The stunned areas continue to survive on anaerobic metabolism with ATP depletion, resulting in shortage of energy for healing processes. Yet, these areas can regenerate with enhanced oxygen supplementation (7).

Further research is needed to correlate the oxygenation improvement by HBOT to different brain areas with the functional improvement (or lack of) to different neurobehavioral domains, in order to construct a dose-response curve to oxygen. It is quite possible that the 70-100 treatments we adopted from Stoller may not be sufficient to  ”lighten- up” certain areas and certain functions. This later on may be the basis for personalized HBOT for FASD.

In conclusion, HBOT shows preliminary but highly promising evidence of offering children and young adults with FASD a first ever genuine chance of improvement of their dire prognosis.

Controlled studies should be conducted in several programs worldwide.

 

References:

1)      Lemoine P, Harousseau H, Borteyru JP, Menuet JC. Children of alcoholic parents--observed anomalies: discussion of 127 cases. Ther Drug Monit. 2003 Apr;25(2):132-6.

2)      Jones KL, Smith DW Recognition of the fetal alcohol syndrome in early infancy. Lancet. 1973 Nov 3;302(7836):999-1001.

3)      Goodlett CR, Horn KH.  Mechanisms of Alcohol-Induced Damage to the Developing Nervous System. Dev Neurobiol. 2012 Oct; 72(10): 1302–1316

4)      ) Stoller KP. . Quantification of neurocognitive changes before, during, and after hyperbaric oxygen therapy in a case of fetal alcohol syndrome. Pediatrics. 2005 Oct;116(4):e586-91

5)      Hyperbaric oxygen therapy. https://www.mayoclinic.org/tests-procedures/hyperbaric-oxygen-therapy/about/pac-20394380  Accessed August1, 2019

6)      Koren G, Golan C, Suzin G et al. Effects of Hyperbaric Oxygen Therapy on Brain Perfusion, Cognition and Behavior in Fetal Alcohol Spectrum Disorder-A Case Study. Alcohol Alcohol. 2019 Mar 1;54(2):177-179.

7)      Efrati S, Ben-Jacob E. Reflections on the neuroprotherapeutic effects of hyperbaric oxygen. Expert Rev Neurother . 2014; doi 10.1586/1473175.2014.884928