Discussion
The injury the patient suffered in the accident damaged numerous nerve
structures in his body. The primary damage, which had been caused by
mechanical force, stretched and disrupted his nerve cells. This
condition is known as diffuse axonal injury.
Cells affected by primary injury trigger inflammatory reactions, which
lead to cerebral oedema and increased intracranial pressure. In
addition, the resulting haematomas and inflammation, which accompanied
blood extravasation, caused swelling of the adjacent tissue and
aggravated dysfunction of the nervous tissue. The lesions resulting from
the injury intensified the increase in the intracranial pressure, which
subsequently caused a decrease in the cerebral perfusion pressure. The
intracranial lesions caused the compression of undamaged vessels and
reduced the flow in them. Secondary injury disordered the cerebral blood
supply and resulted in the hypoxia of more distant and peripherally
located parts of the brain. In the region where the perfusion of
tissues is reduced, nerve cells receive too little oxygen to function
properly. Therefore, their metabolism slows down and they become dormant
to prevent apoptosis. This ischaemic damage is potentially reversible
and it can be treated by HBOT. Although indications for the HBOT in CNS
disorders are optional rather than basic, this treatment method is
approved by experts (Knefel et al., 2006).
Due to the increased blood oxygen content, which is maintained for a
long period of time, the availability of oxygen increases and nerve
cells are better oxygenated. When breathing air at atmospheric pressure,
the blood oxygen tension in arterial blood is about 100 mmHg, whereas
the oxygen pressure in tissues is about 55 mmHg. The increase in
atmospheric pressure triples the availability of oxygen to the cells of
the central nervous system. When the pressure is three times higher than
atmospheric pressure and the patient is breathing pure oxygen, the blood
oxygen tension increases to 2,000 mmHg, whereas the tissue oxygen
tension rises up to 500 mmHg (Tibbles et al., 1996). This effect
improves the oxygenation of all tissues and thus the ischaemic area is
reduced. This change increases cellular metabolism, which restores
cellular functions disturbed during the trauma (Daugherty et al., 2004).
Apart from that, hyperbaric oxygen therapy has been proved to limit
post-ischaemic reduction in ATP production and to reduce the
accumulation of lactates in ischaemic tissues (Steward et al., 1989).
The disruption of the mechanism that increases damage to nerve cells has
a neuroprotective effect on the rest of the brain and reduces the extent
of permanent damage.
Another mechanism that may significantly affect the treatment is the
influence of hyperbaric oxygen therapy on vasoconstriction and
vasodilatation of cerebral vessels. After exposure to hyperbaric oxygen
the cerebral blood flow is reduced due to lower concentration of nitric
oxide. An experiment on rats exposed to pressures of 3 and 4 ATA for 30
minutes showed that their regional cerebral flow decreased respectively
by 26-39% and 37-43% and this effect lasted up to 75 min. The effect
persisted longer in the group of the animals which had received nitric
oxide (N(omega)-nitro-L-arginine-methyl-ester) prior to the exposure. In
the same experiment the nitric oxide concentration increased during
further exposure and caused a secondary increase in the regional blood
flow in the brains of all rats (Demchenko et al., 2000).
Harch et al. subjected rats to HBOT 31-33 days after experimental
cerebral contusion. The animals had 80 sessions at a pressure of 1.5
ATA. Improvement in behavioural and neurobiological outcomes was
assessed in the study. The animals’ blood vessel density was measured
bilaterally in the hippocampus by means of diaminobenzidine staining and
correlated with the results of behavioural tests. Vascular density in
the damaged hippocampus increased significantly. In consequence, spatial
movement in the group subjected to HBOT increased significantly, as
compared with the control groups (Harch et al., 2007). Repeated exposure
stimulates the growth of blood vessels by increasing the secretion of
the vascular endothelial growth factor (VEGF) by macrophages.
Experimental studies showed that the HBOT brought significantly better
results in mice after brain injury, both in the cognitive and motor
range (Baratz-Goldstein et al. 2017).
The production of oxygen free radicals stimulates anti-inflammatory
mechanisms, which later reduce cerebral oedema and thus compensate for
the re-expansion of blood vessels. A study conducted on mice with
induced brain injury showed that the interleukin-10 level increased,
whereas cerebral oedema decreased as early as 3 hours after hyperbaric
oxygen therapy at a pressure of 2 ATA (Chen et al., 2014). Three
exposures to hyperbaric conditions at a pressure of 2 ATA reduced the
inflammatory markers and increased the number of new endothelial and
glial cells (Lin et al., 2012). Another study showed that after HBOT the
caspase-3 and interleukin-8 levels as well as the tumour necrosis factor
alpha level (TNF-α) decreased (Zhang et al., 2014). The intensity of
free radical production and lipid peroxidation was investigated in an
experiment on rabbits with total brain ischaemia induced for ten minutes
by infusion of artificial cerebrospinal fluid into the subarachnoid
space. Next, immediately after reperfusion the test group was placed in
a hyperbaric chamber at a pressure of 2.8 ATA for 75 minutes. Meanwhile,
the control group breathed atmospheric air. The concentrations of
oxidised and free glutathione and malondialdehyde were measured in the
experiment. The neurophysiological symptoms of brain damage were
assessed by analysing the cortical somatosensory evoked potentials. The
production of oxygen free radicals increased in the test group exposed
to the hyperbaric environment, because there was a higher ratio of
oxidised to reduced glutathione. Lipid peroxidation was comparable in
both groups, as evidenced by the malondialdehyde level. The
somatosensory evoked potentials were as much as 50% higher in the group
of rabbits subjected to hyperbaric oxygen therapy (Mink et al., 1995).
The publications discussed above described laboratory tests on animals
and the period directly related to the moment of TBI. It is extremely
difficult to use HBOT in humans in the immediate period after TBI. The
problem of HBOT efficacy in people in the late period following damage
to the central nervous system (CNS) should be carefully evaluated,
because to date there have been few studies describing the problem.
Efrata et al. described the beneficial effects of HBOT applied in the
neurological rehabilitation of 74 patients after stroke. They had 40
HBOT sessions at a pressure of 2 ATM for two months. The hyperbaric
treatment improved the patients’ neurological functions, including
speech, more than the standard treatment applied to other patients
(Efrati et al., 2013). The patient described in our case study had TBI
rather than acute CNS ischaemia, but in TBI pathogenesis massive blood
supply disorders are an important link in the CNS pathology chain, so
the possible positive effect of HBOT in TBI can also be broadly taken
into consideration. In our case the patient had a similar number of HBOT
sessions.
The following areas are particularly vulnerable in TBI: the frontal
area, the subfrontal white matter, the deeper midline structures
including the basal ganglia and diencephalon, the rostral brain stem,
and the temporal lobes including the hippocampi. In the course of TBI
the catecholaminergic and cholinergic relay systems, which are involved
in the regulation of arousal, cognition, reward behaviour and mood, are
particularly vulnerable. Damage to the dorsolateral prefrontal cortex
impairs executive functions. The orbitofrontal cortex is responsible for
intuitive social behaviours. The third important system is the neuronal
system related to the anterior cingulate cortex, which is involved in
reward-related behaviours (McAllister, 2011). Imaging tests conducted on
our patient revealed structural damage to similar regions, which was
reflected by his cognitive status. During the HBOT the patient’s
cognitive functions and behaviour improved significantly.
Golden et al. made a statistical analysis of 50 patients after TBI who
underwent SPECT before, during and after hyperbaric oxygen therapy. The
results of this analysis confirmed the hypothesis that HBOT improved
blood supply in the cortex, while the therapy had no effect on the
region of the pons and cerebellum. The blood supply was better in
younger patients, but the improvement in functions was comparable in
both groups (Golden et al., 2009). In the context of the research
conducted by Golden et al., it was justified to apply HBOT to our
patient due to his young age and the fact that traumatic lesions were
mostly located in his cerebral cortex. Boussi-Gross observed that
treatment in a hyperbaric chamber improved the quality of life of
patients after TBI. The researcher suggested that neuroplasticity played
a role in improvement of chronically impaired brain functions
(Boussi-Gross et al., 2013).
Hadanny et al. described the use of HBOT in a distant time after brain
damage. The study was conducted on patients who had suffered brain
injury 3 months to 33 years before. A team of scientists observed
significant improvement in cognitive functions in correlation with an
increase in the neurological activity in individual parts of the brain.
After the HBOT the patients’ memory and attention usually improved
(Hadanny et al., 2018).
In our case the patient was qualified for HBOT due to the persistence of
severe cognitive deficit. He was qualified for the treatment with due
caution. The patient did not develop epilepsy, which might have
disqualified him from therapy. The potential pathogenic effect of the
concomitant chest injury was also taken into consideration. However, the
patient did not develop pneumothorax despite numerous rib fractures. As
the time interval between the injury and HBOT allowed full recovery from
respiratory pathologies, there was low risk of lung damage during the
HBOT.
The case described in this article documents the effectiveness of using
HBOT to treat the patient after a severe TBI injury complicated by
significant sensory aphasia. Significant neurological complications can
be expected after such a severe injury, because there is a linear
correlation between the GCS score and the occurrence of severe
neurological disorders within a GCS range of 3-9 (Hukkelhoven et al.,
2006).
It is disputable whether the observed neurological improvement resulted
from the natural course of the disease or it was accelerated by the
HBOT. According to reference publications, the language disorder tends
to disappear naturally within 1-3 months (Wood, 1990). As our patient
had severe cognitive impairment after 5 months of ITU treatment, we can
assume that the changes regressed extremely slowly and the risk of
chronic cognitive impairment was high. In the context of the
aforementioned reports, we can hypothesise that the HBOT had beneficial
effect on our patient. According to recent reports, treatment in a
hyperbaric chamber is safe and beneficial to patients after a traumatic
brain injury and those with symptoms of post-traumatic stress disorder
and post-concussion syndrome (Harch et al., 2017).
Another aspect to be taken into consideration is the patient’s higher
cognitive level before the TBI. According to the cognitive reserve
theory, patients with initially higher IQ and higher level of education
function cognitively better after TBI. Kesler et al. compared the total
intracranial volume (TICV) and ventricle-to-brain ratio (VBR) by means
of high-resolution magnetic resonance imaging. They also analysed the
level of education and used standardised tests to compare the cognitive
outcome of 25 patients before and after TBI. The results of this study
suggest that a larger premorbid brain volume and a higher level of
education may decrease vulnerability to cognitive deficits following
TBI, which is consistent with the cognitive reserve concept (Kesler et
al., 2002). There was an analogous situation in our study, because HBOT
was applied to the patient with a high initial level of education
(patient’s IQ before TBI unknown). Therefore, the patient’s high
cognitive reserve may have influenced the positive outcome of HBOT.
Currently there are only 12 hyperbaric oxygen therapy centres in Poland,
which are mostly located in large medical centres. Therefore, there are
limited possibilities to apply this therapy in common TBI cases.
Additional experience in optional HBOT uses may be a source of important
information broadening our knowledge and the scope of therapy applied to
our patients. As the awareness of healthcare workers concerning this
therapeutic option in TBI is increasing, the application of HBOT may
extend and result in secondary assessment of its effectiveness in
patients with CNS pathology.
In the future studies comparing the results of rehabilitation with
various HBOT schemes may be the basis for modification and extension of
the current treatment scheme for patients with TBI.