Baló's concentric sclerosis is a disease in which the white matter of the brain appears damaged in concentric layers, leaving the axis cylinder intact. It was described by József Mátyás Baló who initially named it "leuko-encephalitis periaxialis concentrica" from the previous definition, and it is currently considered one of the borderline forms of multiple sclerosis.
Baló's concentric sclerosis is classified as an inflammatory demyelinating disorder of the central nervous system, distinguished from classical multiple sclerosis by the characteristic formation of concentric rings of demyelination alternating with preserved myelin. Although earlier reports suggested that the prognosis resembled that of Marburg variant multiple sclerosis, more recent case series and reviews have described patients experiencing more favorable outcomes, including asymptomatic periods, spontaneous remission, or prolonged disease stability.
Cases of Baló's concentric sclerosis have been observed to follow a range of courses, with the majority showing a single acute phase, while others demonstrate either a relapsing-remitting pattern or progression similar to aggressive forms of multiple sclerosis. Although historically considered rare, with fewer than 1% of multiple sclerosis cases showing the characteristic ring-shaped demyelination pattern, Baló's concentric sclerosis is now recognized globally, rather than being geographically confined to Asian populations as once believed.
The concentric ring appearance is not specific to Baló's concentric sclerosis. Concentric lesions have also been reported in patients with neuromyelitis optica, standard multiple sclerosis, progressive multifocal leukoencephalopathy, cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy, concomitant active hepatitis C and human herpes virus 6.
History Although the disease is most commonly associated with the work of Hungarian pathologist József Mátyás Baló, the first descriptions of concentric demyelinating lesions were provided by Otto Marburg in 1906, who documented cases presenting with rapidly progressive neurological decline and distinctive histopathological findings.
During much of the 20th century, Baló's concentric sclerosis was considered a rare and often fatal demyelinating disease, closely linked to tumefactive variants of multiple sclerosis. The disease was characterized by rapidly progressive neurological decline and distinctive concentric demyelinating lesions, leading to its classification as a variant of multiple sclerosis. However, evolving pathological and imaging studies have since suggested that BCS represents a distinct clinicopathological entity within the broader spectrum of demyelinating diseases.
Pathophysiology
The lesions of the Baló's sclerosis belong to the MS lesion pattern III (distal oligodendrogliopathy). Balo concentric sclerosis is now believed to be a variant of pattern III multiple sclerosis probably due to immune problems.
The Baló lesions show veins at their center, like those of MS, some suggestive of microhemorrhages or small ectatic venules. Unlike MS, no cortical gray matter lesions appear. Evidence from immunopathological studies suggest that, unlike other MS subtypes where demyelination is diffuse, the pathological hallmark of Baló lesions is the presence of sharply defined alternating layers of demyelinated and myelin-preserved tissue, indicative of a distinct pattern of immune-mediated attack combined with hypoxia-like stress. Histopathological investigations have observed that these lesions often contain a central vein and display organized concentric rings, supporting the view that vascular factors and microcirculatory impairment might play a role in their formation.
Theoretical Model Mitochondrial dysfunction, particularly involving impaired complex IV activity within the respiratory chain, has also been proposed as a contributing factor to tissue damage in Baló lesions, where such deficits may exacerbate axonal injury through glutamate-mediated excitotoxic mechanisms similar to those identified in pattern III multiple sclerosis lesions. This expression and counter-expression forms rings of preserved tissue within the lesion and rings of demyelinated tissue just beyond where the previous attack had induced the protective stress proteins. Hence, subsequent attacks form concentric rings. Support for this model comes from findings of increased expression of heat shock proteins such as HSP70 and hypoxia-inducible factors (HIF-1α) in Baló lesions, which are believed to protect surrounding tissue and promote survival of axons and glial cells within the demyelinated areas. These stress responses may allow for periods of remission or tissue recovery in certain patients.
In parallel to these hypoxia-related mechanisms, researchers have emphasized the potential role of mitochondrial dysfunction in lesion development. In particular, reduced activity of complex IV or the respiratory chain has been proposed to result in cellular energy deficits that amplify glutamate-mediated excitotoxic injury, a process also recognized in pattern III multiple sclerosis lesions. Studies suggest that the survival of astrocytes within lesions may also contribute to the potential for remyelination, as preserved astrocytic function and support oligodendrocyte precursor cells and restore water balance in the affected tissue. This recovery capacity has been highlighted in case reports of Baló disease patients showing substantial neurological improvement over time without aggressive immunotherapy.
This model is questioned by recent reports that found astrocyte damage, similar to the one found in aquaporin-seropositive neuromyelitis optica. Though no anti-NMO antibodies have been found, the damage is similar, pointing to problems in the water channel of the astrocytes. Recent observations of aquaporin-4 and aquaporin-1 depletion within Baló lesions even in the absence of detectable antibodies, suggests astrocytic injury plays a more role in the pathogenesis than previously thought.
Other Models A mathematical model for concentric sclerosis has been proposed. Authors review the previous pathogenic theories, discuss the link between concentric sclerosis and Liesegang's periodic precipitation phenomenon and propose a new mechanism based on self-organization. This model proposes that the layered pattern of Baló lesions may emerge from physicochemical self-organization processes within the damaged brain tissue, similar to Liesegang ring formation in chemistry, where periodic precipitation patterns result from reaction-diffusion mechanisms.
Clinical courses
More recent observations of Baló's concentric sclerosis describe a wider spectrum of clinical presentations, including relapsing-remitting and monophasic forms. While the disease can progress aggressively, several case reports have documented patients with prolonged stability or spontaneous remission, even in the absence of disease-modifying therapy. High-dose corticosteroid therapy such as intravenous methylprednisolone, is often used during acute episodes, but its efficacy in altering the long-term course of Baló's concentric sclerosis remains unclear due to a lack of controlled trials and the confounding occurrence of spontaneous improvement. The variable response to corticosteroids further highlights the unpredictable nature of Baló's concentric sclerosis.
Baló lesions can undergo radiological resolution over time, particularly in monophasic cases, yet some patients experience evolution to relapsing-remitting multiple sclerosis (RRMS), underscoring the potential for disease progression despite initial remission. Based on clinical observations, Baló's concentric sclerosis has been categorized into three phenotypic patterns: monophasic, relapsing-remitting, and primary progressive forms.
Cerebrospinal fluid (CSF) studies in Baló's concentric sclerosis typically show normal findings or mild mononuclear pleocytosis. Unlike classical Multiple sclerosis, CSF-restricted oligoclonal bands are identified only in a minority of cases, emphasizing the immunological differences between Baló's concentric sclerosis and multiple sclerosis.
The presence or absence of oligoclonal bands, as well as the clinical subtype at presentation does not consistently predict disease outcome, as some monophasic cases may remit spontaneously while others progress despite treatment. The behavior of Baló lesions is also influenced by the disease context in which they occur. These lesions have been reported in patients with aquaporin-4 seropositive and seronegative neuromyelitis optical spectrum disorder (NMOSD), where they may coexist with optic neuritis or longitudinally extensive transverse myelitis.
Diagnosis
Baló's concentric sclerosis is primarily diagnosed through characteristic findings on magnetic resonance imaging (MRI), supported by cerebrospinal fluid (CSF) analysis and, in some cases, histopathological evaluation. The hallmark radiological feature is the appearance of concentric layers of demyelinated and preserved white matter, producing alternating hyperintense and hypointense bands on T2-weighted and FLAIR sequences. These lesions are typically large and tumefactive, often located in the cerebral hemispheric white matter, particularly the frontal and parietal lobes, but can also involve the corpus callosum, brainstem, or spinal cord.
Use of high-field 7-Tesla MRI has further refined lesion visualization, often revealing a central vein within Baló lesions, which supports the view of a perivenular pathogenesis similar to classical MS. Magnetic resonance spectroscopy (MRS) has demonstrated increased lactate and decreased N-acetylaspartate within Baló lesions, indicating active inflammation and neuronal loss, while diffusion tensor imaging (DTI) shows decreased fractional anisotropy, reflecting white matter damage. These imaging markers are highly consistent with histopathological features, enabling radiological-histopathological correlation and reducing the need for invasive biopsy in most cases.
CSF analysis in Baló's concentric sclerosis typically shows either normal findings or mild mononuclear pleocytosis, but differs from classical multiple sclerosis in that CSF-restricted oligoclonal bands are present only in a minority of cases. Pattern III lesions, including Baló's concentric sclerosis, also tend to test negative for the MRZ reaction, which detects intrathecal responses to measles, rubella, and varicella zoster virus, further distinguishing them from standard multiple sclerosis.
In pediatric populations, Baló's concentric sclerosis has been observed to have a more variable clinical course, with some children exhibiting favorable outcomes and lesion resolution on imaging, while other experience severe presentations similar to adult forms. Baló lesions have been identified in children presenting with acute disseminated encephalomyelitis (ADEM)-like features, reflecting the overlap of concentric lesion morphology across multiple demyelinating syndromes.
Treatment
Acute Management
High dose intravenous corticosteroids, such as methylprednisolone, are commonly administered as first-line therapy for acute Baló's concentric sclerosis episodes to reduce inflammation and stabilize the blood-brain barrier. However, responses to corticosteroids can be variable, with some patients exhibiting limited improvement.
Immunosuppressive and Disease-Modifying Therapies
Given the overlap of Baló's concentric sclerosis with other demyelinating disorders, various immunosuppressive agents have been explored: