Introduction

Balo disease is a rare variant of tumefactive demyelinating disease (TDL), with quite low numbers of reported cases.¹ This disease results in the loss of the protective coating—the myelin sheath—of the nerve fibres in the nervous system, a process known as demyelination that leads to swelling (tumefaction).

For a condition to be considered TDL, a lesion must exceed two centimetres. However, due to the current diagnostic equipment available, it has been quite difficult to specifically distinguish conditions as Balo disease. For example, the TDL may be easily covered and diagnosed as high-grade gliomas, which are the accumulation of cells around the nerve cells.

Multiple sclerosis (MS) is the leading cause of most cases of Balo disease and TDL in general. MS is an autoimmune disease where the immune cells attack the brain and spinal cord. Balo disease is a more advanced MS, where the lesions may be so deep that the grey matter of the brain is affected.²

Understanding environmental factors and their effect is important to help make the connection between them and risk factors. Environmental factors include our exposure to specific substances (e.g., pesticides or waste), where we live or work, our behaviour and the effects it may have.

Environmental factors, such as pollution levels in the areas we live in or smoking and diet habits, can have complex interactions with genetic factors, leading to genetic damage and causing the disease.

This article will explore the links between environmental triggers and Balo disease.

Balo disease: an overview

Balo disease is known by its concentric layers of demyelination. The research into the disease is still quite incomplete, with the difference between MS and Balo not being completely known. The determinants of Balo itself are not entirely clear, as it hasn’t been strictly classified as a disease in its own right. Consequently, this article draws some information from studies primarily focused on MS patients. However, it is known that the development of MS can lead to Balo disease.

Many studies are currently underway to understand the difference between the diseases, with the most recent suggesting that Balo disease cuts three layers deeper into the myelinated sheath.³

Balo disease itself is very severe, and within a few months of the disease, many cases have quickly progressed into conditions such as paralysis and seizure. Quite frequently, many cases have advanced to mortality, proving to be a very dangerous autoimmune disease.⁴

The disease is quite rare, and it is most commonly discovered among people of Han Chinese and Filipino descent. However, surprisingly, multiple sclerosis is typically less common in these groups compared to Caucasians. The reason for this is currently unknown.⁵

Differentiating Balo disease from multiple sclerosis

Different types of advanced MS lead to different diagnoses. The main difference is the presence of concentric rings on magnetic resonance imaging (MRI) in Balo disease, formed by the alternating bands of demyelinated and myelinated white matter.³

Treatments

Currently, there are no treatments available to specifically cure Balo disease. Corticosteroids are widely used for all forms of MS to try and reduce the recovery period after flare ups. The treatment is believed to speed up the recovery from a flare-up if it is used for 3-5 days; however, it has no effect on reducing the chances of an upcoming flare-up.⁶

Environmental factors leading to Balo disease

Understanding the environmental factors that specifically lead to Balo disease is extremely difficult as there is limited research on the disease due to its rare occurrence. Therefore, this article will focus more on the environmental factors that lead to MS, and further how these conditions interact with genetic factors to increase the likelihood of MS developing to Balo disease.

Most of the current research suggests a strong link between Epstein-Barr Virus (EBV) infection, smoking, sun exposure, or obesity and the risk of MS. Smoking, EBV infection, and obesity all interact with certain risky versions of human leukocyte antigen (HLA), which only some people have, increasing their risk for MS. 

HLA genes train the immune system to recognise one’s own body cells. However, their risky versions, when combined with the environmental factors, can lead to a pathogenic immune pathway that likely attacks the myelin in the nerve fibres.

Recent studies have shown the importance of lifestyle and environmental factors as causes of MS and its possible development into Balo disease, in comparison to genetic predisposition. Genes take generations to significantly change, meaning that a majority of these increases in MS rates are due to lifestyle changes over the years.⁷ 

Smoking

Smoking has a clear relationship with increasing the risk of MS. The higher the cumulative dose of smoking, the increased risk of MS. Even second hand smoke, or any form of lung irritation, is a contributing factor to MS.⁷

Smoking is harmful for autoimmune diseases, as it increases inflammation through the constriction of blood vessels. Research shows that, in general, lung irritation can activate immune responses to biologics and a lot of organ-specific inflammatory diseases.

Smoking leads to protein modifications in the body that are treated as foreign and attacked by the immune cells. In addition, the inflammation caused by smoking can activate the immune cells to target the central nervous system (CNS) proteins like myelin—CNS autoantigenic cells. These attacks by the immune cells are believed to contribute heavily to the development of MS through the demyelination of nerve cells.

In people with risky versions of the HLA gene, a complex interaction between the risky genes and smoking further increases the risk of contracting MS.

Overall, smoking and general lung irritation are large environmental and lifestyle factors that contribute to an increased risk of MS.⁷ 

Vitamin D and its effects

An increased consumption of vitamin D and fatty acids, as well as significant sun exposure, decreases the risk of MS. Hence, those with a lower exposure to sun and consumption of vitamin D have a higher risk of MS.

Regions with less average sunlight per day have seen more cases of MS compared to areas with more sunlight hours in the day.

High levels of vitamin D are associated with the reduced levels of axonal (part of your neuron) injury, and lower MRI activity, which suggests a slower disease progression. Therefore, vitamin D has proven to be very impactful in strengthening the immune profile of an individual, and contributes heavily to reducing the risk of MS.⁷ 

Get your vitamin D levels checked regularly to get appropriate supplements from a healthcare provider, if need be.

Obesity

Obesity, particularly during adolescence, has been associated with an increased risk of developing MS. Individuals with a body mass index (BMI) above 27 have approximately twice the risk of developing MS compared to those with a normal BMI.⁷

This association is strongest during adolescence and appears to affect both males and females. The link between obesity and MS risk is attributed to:

• An individual’s genetic predisposition to obesity (high BMI)
• An individuals status of risky HLA gene variants
• Interaction between obesity and MS-related genetic risk factors

The mechanisms by which obesity may increase MS risk are not fully understood. However, several potential pathways that activate the immune cells targeting the neurons and triggering the neuroinflammatory (inflammation of nervous tissue) episodes, characteristic of MS, have been proposed.⁷

• Low-grade inflammation: Obesity is characterised by chronic, low-grade inflammation in adipose tissue, which may promote pro-inflammatory immune responses and decrease the function of regulatory T cells (regulates immune response)
• Increased leptin levels: Obesity leads to higher levels of leptin, a hormone associated with pro-inflammatory effects
• Reduced vitamin D bioavailability: Obesity can decrease the bioavailability of vitamin D, which may contribute to a pro-inflammatory state

Obesity and Epstein-Barr virus infection

The interaction between obesity and Epstein-Barr virus (EBV) infection, another MS risk factor, further supports the causal role of obesity in MS development. When combined, these two factors significantly increase MS risk, possibly due to obesity's negative impact on immune responses against EBV or the creation of a more pronounced pro-inflammatory environment.⁷

Understanding the relationship between obesity and MS risk has important implications for prevention strategies, especially for individuals with a family history of MS. It also highlights the potential impact of the global obesity epidemic on MS incidence, particularly among women.

Summary

There is a complex relationship between environmental factors and Balo that is unknown. With the closest available research only connecting to MS, we can still understand that MS is the early-onset condition that progresses to become Balo disease.

There is a strong link between Epstein-Barr Virus (EBV) infection, smoking, sun exposure, or obesity and the risk of MS. Smoking, EBV infection, and obesity all interact with the risky versions of the human leukocyte antigen (HLA), which only some people have, increasing their risk for MS, thereby the Balo disease.