Baló's concentric sclerosis is a disease in which the white matter of the brain shows damage in layers, with the nerve fibers remaining undamaged. It was first described by József Mátyás Baló, who originally called it "leuko-encephalitis periaxialis concentrica." Today, it is considered a type of multiple sclerosis that falls on the edge of being classified as a separate condition.
Baló's concentric sclerosis is an inflammatory disease that affects the central nervous system. It is different from classical multiple sclerosis because it forms alternating layers of damaged myelin (the protective covering of nerve fibers) and areas where myelin is preserved. Earlier reports suggested that the outlook was similar to a rare form of multiple sclerosis called the Marburg variant. However, recent studies show that some patients experience better outcomes, such as periods without symptoms, recovery without treatment, or long-term stability.
Cases of Baló's concentric sclerosis can follow different patterns. Most show a single sudden episode, while others may have repeated flare-ups or progress in a way similar to aggressive multiple sclerosis. Though once thought to be very rare and limited to certain regions, it is now known to occur worldwide.
The layer-like appearance of brain damage is not unique to Baló's concentric sclerosis. Similar patterns have been found in conditions such as neuromyelitis optica, standard multiple sclerosis, progressive multifocal leukoencephalopathy, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and in some cases involving active hepatitis C and human herpes virus 6.
History
Although the disease is most commonly linked to the work of Hungarian pathologist József Mátyás Baló, the first descriptions of concentric demyelinating lesions were made by Otto Marburg in 1906. He recorded cases involving quickly worsening neurological symptoms and unique tissue findings.
For much of the 20th century, Baló's concentric sclerosis was viewed as a rare and often deadly demyelinating disease closely connected to certain types of multiple sclerosis. It was marked by fast-progressing neurological decline and distinct layered areas where myelin was lost, leading to its classification as a form of multiple sclerosis. However, newer studies using pathology and imaging techniques have shown that Baló's concentric sclerosis may be a separate condition within the larger group of demyelinating diseases.
Pathophysiology
The lesions in Baló's sclerosis are a type of multiple sclerosis (MS) lesion pattern known as pattern III (distal oligodendrogliopathy). Baló concentric sclerosis is now considered a variation of pattern III MS, likely caused by immune system issues.
Baló lesions have veins at their centers, similar to those found in MS, which may indicate small blood vessel damage or bleeding. Unlike MS, these lesions do not occur in the outer layer of the brain (cortical gray matter). Studies show that Baló lesions have clearly defined layers of damaged (demyelinated) and healthy (myelin-preserved) tissue, arranged in concentric rings. This pattern suggests a unique immune response combined with stress similar to oxygen deprivation. These layers often surround a central vein, supporting the idea that blood vessel problems and poor blood flow may contribute to lesion formation.
Research also suggests that mitochondrial dysfunction—specifically, reduced activity of a protein complex called complex IV—may harm brain tissue in Baló lesions. This dysfunction could worsen nerve damage through a process involving the chemical glutamate, similar to what occurs in pattern III MS. The alternating layers of damaged and healthy tissue may result from immune attacks that trigger protective stress responses, such as the production of heat shock proteins (like HSP70) and hypoxia-inducible factors (HIF-1α). These responses may help protect nearby brain cells and allow some recovery in affected areas.
In addition to these stress-related mechanisms, mitochondrial issues are thought to play a role in lesion development. Reduced energy production from mitochondrial dysfunction may worsen glutamate-related nerve damage, a process also seen in pattern III MS. Some studies suggest that surviving astrocytes (a type of brain cell) in lesions may support the repair of myelin by helping oligodendrocyte precursor cells and restoring water balance in damaged tissue. This repair ability has been observed in some Baló disease patients who showed improved neurological function over time without aggressive treatment.
However, recent findings challenge this model. Some reports show astrocyte damage in Baló lesions similar to that seen in a condition called aquaporin-seropositive neuromyelitis optica, even though no specific antibodies linked to that condition are present. This suggests that problems with water channels in astrocytes may be involved in Baló lesions.
A mathematical model has been proposed to explain the concentric patterns of Baló lesions. This model compares the layered structure of the lesions to a natural phenomenon called Liesegang's periodic precipitation, where chemical reactions create repeating ring patterns. The model suggests that the alternating layers in Baló lesions may form through similar self-organizing processes in damaged brain tissue.
Clinical courses
Recent studies of Baló's concentric sclerosis show a range of ways the disease can affect the body, such as patterns where symptoms return after improving or cases where symptoms occur only once. While the disease can worsen quickly in some people, reports show that others may have long periods of stability or even recover without treatment. During sudden worsening of symptoms, high-dose corticosteroid treatment, like intravenous methylprednisolone, is often used. However, it is unclear if this treatment changes the long-term outcome of the disease because there are not enough controlled studies, and some people improve without treatment. The different ways people respond to corticosteroids show how unpredictable the disease can be.
Baló lesions, which are areas of damage in the brain, may disappear on imaging tests over time, especially in cases where symptoms occur only once. However, some patients may later develop relapsing-remitting multiple sclerosis (RRMS), which means symptoms return after periods of improvement. Based on observations, Baló's concentric sclerosis is divided into three main types: monophasic (a single episode), relapsing-remitting (symptoms return after improvement), and primary progressive (symptoms worsen steadily over time).
Tests of cerebrospinal fluid (CSF) in Baló's concentric sclerosis usually show normal results or a slight increase in certain types of white blood cells. Unlike classical multiple sclerosis, CSF-restricted oligoclonal bands (a type of protein marker) are found in only a few cases, showing differences in how the immune system is involved in Baló's concentric sclerosis compared to multiple sclerosis.
Whether oligoclonal bands are present or absent, and the type of disease at the start, does not always predict how the disease will progress. For example, some monophasic cases may improve on their own, while others may worsen despite treatment. The behavior of Baló lesions also depends on the larger disease context in which they occur. These lesions have been found in patients with aquaporin-4 seropositive and seronegative neuromyelitis optica spectrum disorder (NMOSD), where they may appear alongside optic neuritis or a specific type of spinal cord inflammation.
Diagnosis
Baló's concentric sclerosis is most often diagnosed using magnetic resonance imaging (MRI), which shows specific patterns. Cerebrospinal fluid (CSF) testing and, sometimes, examination of brain tissue under a microscope also help confirm the diagnosis. The key MRI finding is the presence of alternating layers of damaged and healthy white matter, which appear as bright and dark bands on certain MRI scans. These lesions are usually large and located in the white matter of the brain's frontal and parietal lobes, though they may also occur in the corpus callosum, brainstem, or spinal cord.
High-field 7-Tesla MRI improves the ability to see these lesions clearly, often showing a central vein inside them. This suggests a cause related to veins, similar to what is seen in classical multiple sclerosis. Magnetic resonance spectroscopy (MRS) reveals higher levels of lactate and lower levels of N-acetylaspartate in these lesions, which indicates active inflammation and nerve cell damage. Diffusion tensor imaging (DTI) shows reduced fractional anisotropy, which reflects damage to white matter. These imaging results match findings from tissue samples, helping doctors avoid the need for invasive procedures in most cases.
Cerebrospinal fluid testing in Baló's concentric sclerosis may show normal results or a small increase in white blood cells. However, unlike classical multiple sclerosis, only a few cases show oligoclonal bands in the CSF. Lesions like those in Baló's disease often test negative for the MRZ reaction, which detects immune responses to measles, rubella, and varicella zoster viruses. This helps distinguish Baló's disease from standard multiple sclerosis.
In children, Baló's concentric sclerosis can have different outcomes. Some children may recover with lesion resolution on imaging, while others may experience severe symptoms similar to adult cases. Baló lesions have been found in children with conditions resembling acute disseminated encephalomyelitis (ADEM), showing that similar patterns of damage can occur in different types of demyelinating diseases.
Treatment
High dose corticosteroids, such as methylprednisolone, are often given through a vein as the first treatment for sudden episodes of Baló's concentric sclerosis. These medicines help reduce swelling and protect the blood-brain barrier. However, some patients may not show much improvement from this treatment.
Immunosuppressive and Disease-Modifying Therapies
Because Baló's concentric sclerosis shares features with other conditions that damage nerve coverings, several medicines that weaken the immune system have been tested:
Cyclophosphamide is a type of medicine that suppresses the immune system. It has been used for severe or hard-to-treat cases of Baló's concentric sclerosis, sometimes with other treatments. Rituximab is a monoclonal antibody that targets B cells (a type of immune cell) and has helped patients with signs of immune-related damage. Alemtuzumab is another monoclonal antibody that targets CD52 and removes many immune cells. A case study showed it might help in Baló's concentric sclerosis, though results can vary. Ocrelizumab works like rituximab by targeting B cells and has been shown to reduce lesion size and improve brain function in some cases of Baló's concentric sclerosis.
Supportive Care and Monitoring
Regular MRI scans are important to track changes in brain lesions. Since some cases may improve on their own, treatment plans should be tailored to each patient, considering the risks and benefits of strong immune-suppressing treatments. Care from multiple specialists, including physical and occupational therapy, may help improve movement and daily function, and support overall well-being.
Epidemiology
Baló's concentric sclerosis most often affects people aged 20–40 years, though it can also occur in children and older adults. Unlike multiple sclerosis, which is more common in females, Baló's concentric sclerosis appears to affect males slightly more often. It can occur as a separate condition or be linked to other diseases, such as tumefactive inflammatory leukoencephalopathy, where it may be part of larger abnormal areas in the brain.
Baló's concentric sclerosis has been linked to certain autoimmune diseases, such as psoriasis and autoimmune thyroiditis, though the exact relationship is not yet fully understood and requires further research.
Pattern III (Baló-like) Demyelinating Spectrum
Lesions similar to those in Baló's concentric sclerosis are classified as MS lesion pattern III. These lesions can appear alone or alongside other conditions, including multiple sclerosis, neuromyelitis optica, CADASIL, and progressive multifocal leukoencephalopathy. Some cases of Baló's concentric sclerosis overlap with unusual forms of multiple sclerosis, and a specific type of multiple sclerosis includes Baló-like lesions (pattern III lesions), showing a connection between these two conditions.
Some patients with Baló's concentric sclerosis have oligoclonal bands in their blood, while others do not. Researchers suggest that Baló's lesions may not represent a single disease but could be the final stage of various demyelinating disorders. Recent studies indicate that pattern III lesions respond well to mitoxantrone, a medication, but are less likely to improve with plasmapheresis. These lesions can be diagnosed without a biopsy, as patients often show strong reactions to AQP1 (without antibodies) and varicella zoster virus (VZV).
The cause of Baló's concentric sclerosis and pattern III multiple sclerosis lesions is still debated. Early theories suggested that pattern III lesions might be an early stage of multiple sclerosis plaques, but later studies have questioned this idea, proposing that these lesions may result from a different process. Pattern III lesions are marked by damage to oligodendrocytes (cells that produce myelin) and specific cell death, which differs from the typical features of multiple sclerosis lesions, such as immune cell infiltration and antibody activity. This unique pattern has led scientists to explore other possible causes, such as environmental or infectious factors. One proposed cause involves the bacterium Clostridium perfringens, which produces a toxin called epsilon toxin. A study found C. perfringens in a person who later developed multiple sclerosis, and people with multiple sclerosis show higher immune reactions to epsilon toxin than healthy individuals, suggesting possible exposure.
Evidence also shows that astrocytes (a type of brain cell) play a role in Baló's concentric sclerosis. Studies found that patients lose certain channels (AQP1 and AQP4) in brain areas affected by the disease, even without detectable AQP4 antibodies. This pattern of astrocyte damage is different from that seen in neuromyelitis optica, where AQP4 antibodies are typically present. However, it suggests similar mechanisms may contribute to lesion formation in both conditions. Patients also show strong immune reactions to AQP1, indicating that astrocyte injury may occur through processes other than antibody binding, such as T-cell activity or toxin effects.