Abstract A 15-year-old girl diagnosed with FASD underwent 100 courses of hyperbasic oxygen therapy (HBOT). Prior to HBOT, single motion emission compute tomographic begin imaging (SPECT) revealed areas of hypo-perfusion bilaterally in the orbitofrontal region, temporal lobes and right dorsolateral—frontal, as well the medial aspect of the left cerebellum. Following two sets of HBOT treatments (60 plus 40), over 6 months, there was improvement in perfusion to the left cerebellum as well as the right frontal lobe. This was paralleled by improvement in immediate cognitive tests and an increase in functional brain volume. A follow-up 18 months after HBOT showed sustained improvement in attention with no need for methylphenidate, as well as in math skills and writing.

1. Alcohol and Alcoholism, 2019, 1–3
doi: 10.1093/alcalc/agz009
Rapid Paper
Rapid Paper
Effects of Hyperbaric Oxygen Therapy on Brain
Perfusion, Cognition and Behavior in Fetal
Alcohol Spectrum Disorder—A Case Study
Gideon Koren1,2,3,4,
*, Chaim Golan5
, Gil Suzin5
, Matitiahu Berkovich1,2,3
,
and Shai Efrati2,5
1
Motherisk Israel Program, Israel, 2
Maccabi-Kahn Research Institute, Israel, 3
Clinical Pharmacology Unit, Assaf
Harofh Medical Center, Israel, Tel Aviv University, Israel, 4
Ariel University, Israel, and 5
Hyperbaric Medicine Unit,
Assaf Harofe Medical Center, Israel
*Corresponding author: Maccabi Kahn Research Institute, 4 Koifman St. 8th floor, Tel Aviv 6812509, Israel. Tel:
972587194777; E-mail: gidiup_2000@yahoo.com
Received 19 November 2018; Revised 13 January 2019; Editorial Decision 18 January 2019; Accepted 12 February 2019
Abstract
A 15-year-old girl diagnosed with FASD underwent 100 courses of hyperbasic oxygen therapy
(HBOT). Prior to HBOT, single motion emission compute tomographic begin imaging (SPECT)
revealed areas of hypo-perfusion bilaterally in the orbitofrontal region, temporal lobes and right
dorsolateral—frontal, as well the medial aspect of the left cerebellum. Following two sets of HBOT
treatments (60 plus 40), over 6 months, there was improvement in perfusion to the left cerebellum
as well as the right frontal lobe. This was paralleled by improvement in immediate cognitive tests
and an increase in functional brain volume. A follow-up 18 months after HBOT showed sustained
improvement in attention with no need for methylphenidate, as well as in math skills and writing.
Fetal alcohol spectrum disorder (FASD) is the most prevalent known
cause of congenital developmental delay in the USA, affecting up to
5% of children (May et al., 2018). While the mechanisms by which
ethanol adversely affects the developing brain are debated, the damage
has been typically characterized as static encephalopathy (Goodlet and
Horn, 2015). Presently, there are no specific forms of therapy for
FASD, and neurobehavioral deficits are addressed by cognitive and
behavioral approaches and symptomatic pharmacotherapy (Ozsarfati
and Koren, 2015; Coles et al., 2018)
Hyperbaric oxygen therapy (HBOT) is a method of delivering
increased inspired oxygen fraction at increased ambient pressure
(Hyperbaric oxygen therapy, 2015). The FDA has approved HBOT
for the treatment of decompression sickness, gas embolism, carbon
monoxide and cyanide poisoning, skin grafts and flaps and thermal
burns.In recent years the medical community has examined HBOT
for a variety of additional indications, but its effectiveness in these
indications is unclear (Hyperbaric oxygen therapy, 2015).
In 2005, Stoller described cognitive improvement in a 15-year-old
boy with FASD after undergoing 73 HBOT treatments,, each
consisting of 60 minutes of 100% oxygen at 1.5 atmospheres absolute.
At a six month follow-up the boy maintained his gains in verbal mem-
ory, and improvement in impulsive behavior (Stoller, 2005).
Presently, the mechanisms by which HBOT may improve cogni-
tive function in FASD have not been studied.
We describe the case of a 14-year-old girl with FASD treated by
HBOT, in whom cognitive functions and single proton emission
computed tomographic brain imaging (SPECT) were studied before
and following HBOT (100 treatments).
Case: A 14-year-old girl was adopted at 5 months of age from a
home for deserted children in the former Soviet Union. At the time
of adoption she suffered from malnutrition and a profound develop-
mental delay. Throughout her childhood, she exhibited severe learn-
ing disability, attention deficit, hyperactivity and impulsivity
responding well to methylphenidate, as well as learning disability
and cognitive delay. At 14 years of age, she was diagnosed with
FASD, based on a history of heavy maternal drinking, normal facial
features and severe neurocognitive and behavioral deficits in multiple
domains (Alcohol-related neurodevelopmental disorder, ARND).
© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved. 1
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2. A brain MRI, conducted prior to commencing the HBOT,
showed normal anatomy. Prior to starting the HBOT, her achieve-
ments on Neurotrax and Global Mindstreams (Dwolatzky et al.,
2003; Neurotrax, 2004) confirmed impaired memory and attention,
impulsivity, and reduced executive function and verbal performance.
She underwent 60 plus 40 additional HBOT treatments each
consisting of 60 minutes of 100% oxygen at 1.5 atmospheres abso-
lute over 6 months. Her mother was with her in the chamber and
occupied her with films, computer games and some homework.
There was an improvement between 1st and 2nd testing (6 months
apart) in her verbal abilities and in the speed of processing informa-
tion. Attention Focus (Go-no Go) improved from 93 to 105, speed
of response from 86 to 95, verbal memory from 30% to 40%, and
naming from 63 to 85. All Mindstream scores are presented using a
psychometric curve (mean = 100; SD = 15).
The improvement in cognitive function was associated with
improved daily functioning allowing her to better plan her daily
schedule and her ability to relate to people around her. She appeared
less tense, with improved abilities to stand and talk in class and to
read and write. In contrast, there was no evidence of improvement in
impulsivity, with continuous impaired memory and other difficulties.
Brain SPECT analysis was performed with NEUROGAMTM
soft-
ware. Brain SPECT studies were normalized to maximal cortical activ-
ity excluding cerebellar activity. Pre and post HBOT SPECT Images
are presented as % of maximum brain activity (upper two rows).
The bottom row represents the % change in brain activity after
HBOT (Fig. 1).
SPECT imaging at baseline prior to HBOT revealed 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 two sets of HBOT treatments (60 plus 40, including
some sessions conducted on holidays), 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 (Fig. 1).
A follow-up 2 years after completion of the HBOT revealed,
based on parents’ and teachers’ reports, that the HBOT was asso-
ciated with clear and sustained improvement in attention, in under-
standing mathematical concepts, in writing comprehension of text,
and with less grammatical errors.
The effect on impulsivity has declined over time. There is still
heightened stress and restlessness especially where she is demanded
to maximize her abilities.
Our case provides objective evidence of improvement in both
cognitive function, as well as in perfusion to specific brain regions.
Her parents had been attentive in the months prior and we do not
believe the improvement in cognition and behavior (or the improve-
ment in imaging results) is attributable only to the 6 months of pro-
grammed maternal attention and focus. The cognitive improvement
corroborates the findings attributed to HBOT by Stoller in 2005.
The present case adds for the first time physiological evidence that
HBOT improves perfusion to critical brain regions, in FASD, as
measured by SPECT.
This has not been an area of research in the studies of the patho-
genesis of FASD. Out of the numerous proposed mechanisms of
fetal alcohol brain insult (Goodlet and Horn, 2015) several may be
relevant here, to explain the reversible nature of the damage by
hyperbaric oxygen: Neuronal death can be induced by excess activ-
ity of certain neurotransmitters, including glutamate. This phenom-
enon, excitotoxicity, may also contribute to alcohol-related damage
to the developing brain. Some of the harmful effects of prenatal
alcohol also may also be associated with alcohol-induced disruption
of brain’s glucose transport and uptake, or altered developmental
regulation of gene expression.
Fig. 1. Changes in brain perfusion over 6 months associated with HBOT in the case. SPECT Images are presented as % of maximum brain activity (upper two
rows). The bottom row represents the % change in brain activity after HBOT.
2 Alcohol and Alcoholism
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3. If the putative effect of HBOT on FASD can be documented
in an appropriately powered study, this may offer a unique
non-pharmacologic solution to many children affected by
FASD.
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3Alcohol and Alcoholism
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