According to reports, Balo’s concentric sclerosis (BCS) tends to occur in young individuals, with an average onset age of 34 years. The incidence of BCS in females is reported to be twice that in males, and it is more prevalent among patients in East Asian countries[4]. Depending on the location of the lesions, patients may exhibit acute or subacute symptoms. Generally, BCS presents with more severe cortical dysfunction compared to typical multiple sclerosis, including symptoms such as aphasia, cognitive or behavioral disorders, and seizures[5]. The diagnosis of BCS is typically based on a combination of clinical evaluation, MRI findings, and cerebrospinal fluid analysis.
In summary, the characteristics of the present case are as follows: ①Clinical Presentation: A middle-aged male patient with an acute onset, presenting primarily with cognitive dysfunction and behavioral abnormalities. Pathological signs were present on admission, and improvement was observed with steroid treatment, with the disappearance of pathological signs, suggesting the effectiveness of steroid therapy. ②Cerebrospinal Fluid Analysis: Presence of oligoclonal bands, with lymphocyte subset analysis indicating a decreased proportion of lymphocytes, suggesting immune dysfunction and intrathecal synthesis of immunoglobulins.③Radiological Features: T2/FLAIR high signals, partially elevated signals on DWI, layered appearance of lesions, significant perilesional edema, nodular enhancement on contrast-enhanced imaging, and MRS indicating elevated Cho and Cr peaks with decreased NAA peak. ④Pathological Results: Brain tissue showing loose edema, abundant vacuolated foam cells, and proliferation of hypertrophic glial cells indicative of inflammatory reactive proliferation. Increased proliferation of star-shaped glial cells (Creutzfeldt cells) and extensive lymphocytic infiltration were observed, with no evidence of atypical cells. Further immunohistochemistry revealed positivity for Vimentin, indicating glial cell proliferation and foam cell formation, and GFAP positivity, suggesting the presence of nerve fibers. The uniform staining of star-shaped glial cells ruled out tumors, supporting the consideration of a demyelinating disease. Based on these features, the diagnosis for this case is BCS.
BCS is a rare demyelinating disease with unclear etiology and pathogenesis. Its clinical presentation is complex and often misdiagnosed as stroke, brain tumor, or brain abscess. The classic neuroimaging feature of BCS on MRI is concentric ring-like changes, and the pathological changes in the affected areas indicate primary involvement of the myelin sheath, with relative preservation of axons. This is considered characteristic and serves as the gold standard for diagnosing concentric sclerosis. Given its rarity, to further understand the disease, our research team reviewed 37 cases of typical BCS reported in both Chinese and English literature from 2010 to 2020. Among them, 8 cases underwent brain biopsy, primarily showing glial cell proliferation and demyelinating lesions, as summarized in Table 1. Of these cases, 15 were male, 22 were female, with an average age of 39.7 years. Clinical presentations varied, as did the locations of onset. Cerebrospinal fluid results showed increased cell count in 5 cases, elevated protein in 4 cases, positive oligoclonal bands in 5 cases, and increased IgG index in 2 cases. The main treatment approach was steroid pulse therapy, with some patients receiving a combination of steroids and plasma exchange. One patient was treated with steroids, plasma exchange, and alemtuzumab, while another received steroids, intravenous immunoglobulin, and azathioprine.
Table 1
Basic Information of 8 Typical BCS Patients with Brain Biopsy
Sex | Age | Symptom | Location | Brian biopsy | CSF | Treatment | References |
male | 23 | Numbness on the left side of the face and limb | Right parietal and frontal lobes | Inflammatory changes, gliosis | No | Dexamethasone 4mg, intravenous, Q12h | [6] |
male | 36 | Right limb weakness | • Left frontal lobe | Periaxonal myelin deficiency, reactive glial cell hyperplasia | No | High doses of steroids | [7] |
female | 52 | Speech disorder | Left frontal lobe | The incomplete myelin sheath alternates with the preserved myelin sheath | No oligoclonal tape | Dexamethasone 4 mg, Tid; Methylprednisolone 1000mg, intravenous, Qd | [7] |
male | 56 | Progressive left hand weakness and spasm | Bilateral radiating crown | Lymphohistiocytic inflammation with relative axon preservation and myelin loss | Protein 35 mg/dL, no oligoclonal band | Methylprednisolone 1000mg, intravenous drip, Qd; Antiepileptic medication | [4] |
female | 24 | Dysarthria and double upper limb weakness | Bilateral cerebral hemispheres | A large number of foamy histiocytic infiltrates, a few lymphocytes; Myelin sheath scattered in loss | Slightly increased protein (88.3 mg/dL); No oligoclonal tape | no | [8] |
male | 55 | Left limb weakness | Right anterior central gyrus | demyelinating disease | no | Methylprednisolone 500mg, intravenous drip, Bid, for 3 days | [9] |
male | 41 | Dysarthria and mutism are associated with significant sleepiness and psychomotor disturbances | White matter around the ventricles | Gliosis, swelling of eosinophilic astrocytes, annular around blood vessels. Axon staining shows complete axon length extension. | High albumin level, no oligo-clonal bands, normal IgG index | Take a large dose of methylprednisolone orally for 15 days | [10] |
female | 49 | Slow response, right limb weakness | Bilateral parietal occipital, left frontal lobe | White matter stroma edema, astrocyte reactive hyperplasia, scattered lymphatic cell infiltration, lymphocyte sheath formation around individual small blood vessels, local myelin loss. Proliferating glial cells GFAP(+), CD20(-), CD45RA (+) | Normal, no oligo-clonal band | High dose methylprednisolone shock therapy | [11] |
Cerebrospinal fluid analysis showed mononuclear inflammatory response, elevated protein levels, and occasional oligoclonal bands [12]. The MRI features of Balo's concentric sclerosis (BCS) include alternating concentric rings on T1-weighted images, creating a "bull's eye" pattern on T2-weighted images [13]. This case exhibits these characteristic features. However, other complex patterns have been reported, such as mosaic, rosebud, and double-bar patterns [13–14]. The typical MRI presentation of BCS is an "onion-ring" appearance, consisting of alternating demyelinated and myelin-phospholipid preserved regions [14, 15]. Lesions can be solitary or multiple and may infiltrate from small lesions to involve the entire cerebral hemisphere [4, 16]. In the early stages of the disease, the concentric ring pattern may not be evident, and lesions may mimic features of acute disseminated encephalomyelitis, tumors, or abscesses [12].
High signal intensity in diffusion-weighted imaging on MRI suggests cytotoxic edema and ischemia. This phenomenon, occasionally seen in multiple sclerosis but different from ischemia, persists longer in BCS, up to 4 to 5 weeks [5]. Literature reports indicate that BCS exhibits characteristic biochemical changes, including a decrease in the N-acetylaspartate (NAA)/creatine (Cr) ratio, a reduction in choline (Cho)/Cr ratio, and lactate production. The relative NAA values decrease from the periphery to the center, with higher choline values in the center gradually decreasing toward the lesion's edge [3]. Additionally, acute BCS shows characteristic features in magnetic resonance spectroscopy (MRS), with a decrease in NAA peak, an increase in lactate peak, and elevated choline and lipid peaks [17]. This case's MRS demonstrates a similar trend.
BCS is a rare subtype of idiopathic inflammatory demyelinating diseases [12, 18], with lesions ultimately presenting as diffuse demyelinated plaques [19]. In recent years, scholars have reported that, compared to multiple sclerosis, BCS patients show similarities in oligoclonal protein and immunoglobulin G (IgG) index to neuromyelitis optica. In this case, the cerebrospinal fluid (CSF) analysis also indicates the presence of oligoclonal bands. The typical pathological features of BCS include the loss of oligodendrocytes and demyelinating lesions in the brain white matter [4]. Multiple reactive astrocytes with enlarged nuclei and mitotic granules, known as Creutzfeldt cells, are characteristic of BCS demyelinated plaques [13]. This case's brain biopsy confirmed the presence of proliferative astrocytes in the lesion. However, due to various reasons such as patient factors and advancements in hospital technology, the number of collected pathological biopsy samples remains limited, requiring further research.
In summary, the distinctive features of this case include the involvement of multiple sites, with concentric sclerosis distributed in the bilateral frontal, parietal lobes, and left temporal lobe. Moreover, after contrast-enhanced MRI, nodular and ring enhancement was observed in the bilateral frontal, parietal lobes, and left temporal lobe lesions, a phenomenon rarely reported in other cases. The application of the unique stereotactic minimally invasive brain biopsy technique by our research group further provides a solid basis for understanding the pathological changes and diagnosing this disease.
As there is still no unified treatment protocol for Balo's concentric sclerosis (BCS), steroids are currently the first-line treatment. Reviewing the literature, most patients experience symptom relief through steroid treatment, while some patients may undergo plasma exchange therapy. Following steroid treatment, the patient in this case exhibited significant symptom improvement. However, the lack of imaging follow-up materials at present emphasizes the need for ongoing monitoring and follow-up. By sharing this case, our research group aims to contribute to a deeper understanding of BCS and provide insights that may guide future clinical work.