Introduction

What is multiple sclerosis (MS)?

Multiple Sclerosis is a disease in which the Central Nervous System (CNS), which includes the brain and spinal cord, is attacked by the immune system. It more commonly affects people assigned female at birth (AFAB) than people assigned male at birth (AMAB)  and presents with a large range of symptoms that differ from person to person. There is currently no cure for MS, but there are medicines and treatments to help manage the symptoms and, in some cases, limit its progression.

What is hyperbaric oxygen therapy (HBOT)?

Atmosphere is a unit used to measure pressure, with one atmosphere being the air pressure felt at sea level, which is caused by the weight of the air in the sky. Normal air at one atmosphere of pressure consists of about 21% oxygen, 78% nitrogen and 1% other gases (such as carbon dioxide). Hyperbaric oxygen therapy (HBOT) is the use of pure oxygen in a higher-pressure environment with the intention of producing a beneficial effect for a patient. Patients are put inside a sealed chamber containing pure oxygen, which is pressurised to 1.4 atmospheres or above.¹ This process allows the oxygen within the chamber to deeply penetrate the body, allowing the tissues and blood to have greatly increased levels of oxygen compared to the levels that the body maintains in normal circumstances.¹

Understanding multiple sclerosis

Definition and characteristics of MS

Multiple Sclerosis is a chronic autoimmune disease where your body's immune system mistakenly targets your nervous system. This leads to a range of neurological symptoms which can impact the quality of life of those with MS. In many people, it lowers life expectancy, but on average does not appear to significantly decrease it. Currently, the aetiology (underlying cause) of MS is unknown.^REF Research has shown that several genetic and environmental factors are thought to increase the risks of developing MS (REF).^{REF1 REF2} There are four clinical types of MS: relapsing remitting MS (RRMS), progressive relapsing MS (PRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS). RRMS is the most common, making up around 85-90% of cases.^REF These different types are classified according to the onset of the symptoms and how they present over time. In brief, those affected by RRMS experience short-term periods of functional decline (relapses), which are followed by a partial or complete return to normal function (remission). In between the relapses, there is often no obvious decline in function. 

In the remaining types (PRMS, SPMS, PPMS), there is ongoing damage to the nervous system throughout the course of the disease.^REF

Your nervous system is sheathed in a layer of a fatty substance called myelin. In MS, the characteristic of MS. The sclerotic areas are identifiable using magnetic resonance imaging immune system attacks the myelin layer surrounding the nerves, degrading it until the nerves no longer work properly (demyelination). The demyelinated regions of the nerves that become scarred are called “plaques”. This scarring of the sheath is called sclerosis and is the signature (MRI) techniques.² These plaques lead to neurological symptoms that are variable and present in a range of levels of severity.

Impact on the central nervous system

The central nervous system is made up of the brain and spinal cord. It connects to the peripheral nervous system, which consists of all the rest of the nerves, connecting the central nervous system with the rest of the body, as seen in the image below.^REF

Communication between these two systems with electrical impulses is how the brain controls the various parts of the body. As mentioned above, a myelin layer serves both to protect the central nervous system from damage, as well as to help the system to correctly and efficiently transmit signals to and from the brain. The attacks by the immune system cause inflammation of the nerves and prevent the protective myelin layer from insulating the nerves, making it harder for the nerves to correctly and efficiently transmit their electrical signals. Over time, the scarring makes the nerve cells more damaged and liable to die. 

This prevents the brain from being able to communicate with the rest of the body via the nervous system properly.^REF This therefore leads to the neurological symptoms that those affected by MS experience.

Common symptoms and challenges faced by MS patients

Common symptoms include:

• Problems with thinking, learning and planning
• Difficulty walking
• Difficulty controlling the bladder
• Fatigue (tiredness)
• Muscle stiffness and spasms
• Vision problems
• Numbness or tingling in different parts of the body
• Problems with balance and coordination

These symptoms can lead to many challenges for MS patients. Many of these symptoms are likely to have knock-on effects, impacting the lives of those affected in many more ways than just the initial symptom, for example, a decline in cognitive abilities (thinking, learning and planning), leads to a limitation in activities that an individual can participate in (e.g. learning music or reading), which could lead to a loss of independence and community participation. This reduction in the ability to perform normal activities associated with daily living can be invisible to others, can be isolating, reduces independence and results in reductions of the quality of life experienced by patients with MS.^REF While MS makes life harder for those living with it, there are treatments for both the disease as a whole and for individual symptoms. While most treatments cannot cure the disease or repair the damage already done, these treatments can greatly improve the quality of life for those living with MS by managing the symptoms. Some emerging therapies may be able to halt or reverse the progress of the disease, but have serious, sometimes life-threatening side effects.^REF In addition, there are charities (MS Society, MS Trust), governmental support schemes and online communities all available in the UK to connect with. 

Hyperbaric oxygen therapy (HBOT)

Definition and explanation of HBOT

HBOT is defined as the use of pure oxygen at increased pressures, leading to enhanced levels of oxygen within the body.¹ Oxygen is a key nutrient absorbed by the body, but it is unusual in that it is not absorbed via the digestive system, but rather through the lungs.^REF Oxygen is a key nutrient because it allows for the production of energy by cells using aerobic respiration, which is a process that cells use to produce energy in the form of adenosine triphosphate (ATP).

This allows the blood and tissues to become saturated with oxygen and, therefore, have increased cellular energy production (alongside other things). This means that HBOT can be used to aid repair processes in scenarios where there has been a lack of oxygen to parts of the body (hypoxia) and aid the management of pathological processes such as necrosis or wound healing.^{REF1 REF2} However, as with most things, you can have too much of a good thing. Oxygen is highly reactive, and at pressures higher than 2.8 atmospheres, breathing it can become toxic and harmful side effects are observed. Therefore, due to the chemistry and physics of HBOT, it can be hard to design studies and clinical trials in a manner that is able to fully endorse its use as a standardised treatment regime. However, research is ongoing and predictive models have been developed that may indicate which patients and their conditions are best suited to HBOT.^{REF1 REF2}

Historical context of HBOT use

In 1662, Henshaw, a British physician, introduced hyperbaric medical therapy by placing patients in a pressurised container with air. The further development of hyperbaric oxygen therapy (HBOT) in medical care was impeded when Lavoisier and Seguin observed potential oxygen-derived adverse effects at 100% concentrations in 1789. In 1872, Paul Bert, recognised as the "father of hyperbaric physiology," discovered and documented the physiological foundations of pressurised air within the human body. He also described the neurotoxic effects of oxygen in the human body, leading to the designation of the phenomenon as the Paul Bert effect. Following this, a number of scenarios where HBOT could be utilised began to present themselves as the benefits of HBOT were revealed. One of which was the treatment for divers with decompression illness during WW2, which has continued to be used as a treatment for modern divers today. Subsequently, numerous studies were initiated, leading to the establishment of hundreds of hyperbaric oxygen therapy (HBOT) facilities at the outset of the 21st century.¹

HBOT in multiple sclerosis - the science

Mechanisms through which HBOT may benefit MS patients

As mentioned previously, the underlying causes of MS remain unclear. This makes the prevention of the disease and the development of a cure difficult. The use of HBOT as a treatment for MS remains controversial, with many clinical trials producing conflicting results. However, it is clear that some MS patients have benefited from HBOT, which indicates that it warrants further investigation as a therapy.^REF 

A recent study showed that HBOT was successfully used on a well-established mouse model. The results demonstrated that HBOT was able to interfere with the autoimmune response (where the immune system attacks the host body) and successfully reduced the autoimmune response.^REF It did this by dampening the response of the disease-causing autoimmune cells (T cells) and decreasing the amount of inflammation in the areas being scarred. 

In concert with these effects, HBOT also increased the cells involved in controlling the immune system (immunomodulatory cells), thereby indirectly suppressing the problematic autoimmune T cells.^REF Overall, the exact mechanisms remain unclear, but HBOT appears to impact the inflammatory and autoimmune T cells involved in MS. Therefore, HBOT as an additional therapy appears to complement some of the processes involved in limiting or preventing the progression of the disease, providing some forms of neuroprotection.

Research supporting HBOT

The general consensus from medical literature indicates that there are beneficial effects from receiving HBOT alongside normal treatments.^REF Using HBOT alongside other therapies appears to enhance their protective functions during the progression of neurological diseases, in particular anti-inflammatory responses in patients, which are directly relevant to the inflammatory effects associated with the demyelination of the nerves, characteristic of MS.

In 1970 and 1983, clinical studies showed that HBOT treatment improved the symptoms of MS patients. ^{REF1 REF2 REF3} Following this, a series of 12 clinical trials investigating MS treatment with HBOT failed to show the same results; however, the design was flawed as the studies were not structured in a way that the results were able to be meaningfully compared. This is a theme produced by many articles that both support and reject the success of HBOT as a treatment for MS patients. As with any clinical research, it is hard to manage all of the variables in a study. Many of the studies concerning HBOT in MS do not use models that accurately represent the conditions of the patients, do not group patients according to disease severity, or use different treatment regimes (e.g. different pressures).^REF This makes it hard to clearly show whether or not HBOT is an effective treatment, and determine which mechanisms HBOT impacts to produce these results.

One recent study used collaboration between people with MS, doctors, and scientists to explore how hyperbaric oxygen therapy might help MS symptoms.^REF Many people with MS use oxygen therapy, regardless of the lack of scientific evidence connecting it to disease improvement. A key problem which was highlighted by the study is the limited number of studies using conditions like those experienced by people with MS. This study provided valuable information for researchers on how oxygen therapy affects brain cells in conditions relevant to individuals, according to their experiences. 

Safety considerations and potential side effects

The effects of HBOT can be divided into two parts: oxygen-related and pressure-related. As mentioned previously, oxygen is a vital component of aerobic respiration, which provides most of the cells in the body with energy. Part of the reason oxygen is used in this process is that it is highly reactive and contains large amounts of energy that can be obtained and used by the cell through chemical reactions (storing the energy as ATP). This means that unless controlled carefully, oxygen is liable to cause damage. This is not unlike a petrol fire for example. By itself, petrol is not inherently dangerous, but light it is lit, it catches fire and if not contained, could cause damage. So the more petrol (or oxygen) you have, the more potential for damage. 

Prolonged exposure to high levels of oxygen, or exposure at high pressure, can therefore lead to something called oxygen toxicity, which can impact many of the different parts of the body.^REF This is the most obvious oxygen-related risk of HBOT and is easily manageable by keeping HBOT treatments acute (short) and at pressures where oxygen does not become toxic (less than 3 atmospheres as mentioned earlier). 

The most commonly reported pressure-related side effects of HBOT involve areas of the body containing air (e.g. ears, sinuses, teeth, lungs, bowel, etc.). Once again, these are usually easily manageable by maintaining appropriate compression rates and learning strategies to equalise air cavities (e.g. middle ear clearing techniques).^REF Other side effects include claustrophobia, which can be managed with coaching and anxiolytic medications, eye-related side effects and headaches.^REF

Summary

Summary of key points

MS is a disease impacting the CNS, causing a range of symptoms. It is a chronic autoimmune disease that currently has no proven cure. Vast steps have been made in recent years towards the development of a cure and treatments to manage the ongoing symptoms for people living with MS. The current treatments allow for most patients to maintain a reasonable quality of life, with a minimal decrease in life expectancy in most cases. There are communities and organisations set up to help support and educate those affected by the disease. 

Emphasis on the potential benefits of HBOT for MS

The research that has been published on the benefits of HBOT and HBOT for MS has not been plentiful or hugely consistent. The fact remains that there have been promising results generated using HBOT on MS models and in clinical trials, indicating that it may have some therapeutic value for those affected by MS. There needs to be further research into how and why HBOT benefits some patients and not others, and unification in managing the variables to produce better, more meaningful clinical conclusions. Additionally, the models used in HBOT need to be further refined to reflect the patient experiences and to correctly reveal the mechanisms by which HBOT can help stop or reduce the progression of the disease.

FAQs

Does hyperbaric oxygen therapy help multiple sclerosis?

It has been shown to provide benefits for a range of symptoms experienced by people living with MS (such as improved sleep, bladder control and mood, and a reduction in muscle spasms)^REF, but it is not exactly clear why some MS patients do and some do not experience these benefits.

Who is not a candidate for hyperbaric oxygen therapy?

People who are highly claustrophobic are likely to struggle during the treatment periods within the smaller chambers utilised by the therapy. People with persistent sinus issues or blocked sinuses will be unlikely to utilise the therapy due to the ramifications of being put in a higher-pressure environment.

Why is hyperbaric oxygen therapy controversial?

The current scientific and clinical evidence demonstrating therapeutic benefits is conflicting and remains relatively scarce. Future research is required to determine its effectiveness as a therapy.

Does hyperbaric oxygen therapy help nerve damage?

Hyperbaric oxygen therapy (HBOT) has been shown to reduce inflammation in areas associated with nerve damage in models of MS, and help modulate autoimmune responses, but future research is needed to identify exactly how and why HBOT does this.

How quickly does HBOT work?

Most MS patients require a course of several weeks or more of regular HBOT treatments before they begin to report symptom benefits.^REF