Concentric Sclerosis Research Articles

Clinical and Radiologic Features, Pathology, and Treatment of Baló Concentric Sclerosis.

To describe clinical, radiologic, and pathologic features of Baló concentric sclerosis (BCS) and assess overlap between BCS and other CNS inflammatory demyelinating diseases. Retrospective review of BCS cases from US and Australian tertiary care centers. We identified 40 BCS cases with 38 available MRIs. Solitary MRI lesions were present in 26% (10/38). We saw >1 active concurrent BCS lesion in 45% (17/38). A third (13/38) had multiple sclerosis-suggestive lesions on the index MRI, of which 10 fulfilled Barkhof criteria. In patients with serial MRI performed within 1 month of the index MRI, lesions expanded radially with sequentially increased numbers of T2 hyperintense rings 52% (14/27). Initially nonenhancing or centrally enhancing lesions subsequently developed single or multiple enhancing rings (41%; 9/22) and incomplete enhancing rings (14%; 3/22). Discordance between rings as they appear on apparent diffusion coefficient, diffusion-weighted imaging, and gadolinium-enhanced imaging was observed in 67% (22/33). Aquaporin-4 immunoglobulin G (n = 26) and myelin oligodendrocyte glycoprotein immunoglobulin G (n = 21) were negative in all patients with serum available. Clinical response to steroid treatment was seen in 46% (13/28). A monophasic clinical course was present in 56% (18/32) at last follow-up (median 27.5 months; range 3-100 months). The initial attack was fatal in 10% (4/40). Median time from symptom onset to death was 23 days (range 19-49 days). All 17 patients with pathology available demonstrated typical findings of multiple sclerosis. Patients with active demyelinating lesions all demonstrated oligodendrocytopathy (pattern III). BCS may be a distinct subtype of multiple sclerosis characterized by pattern III immunopathology.

Magnetic Resonance Characteristics of Baló Concentric Sclerosis in Children

BackgroundBaló concentric sclerosis is a rare demyelinating disease with characteristic magnetic resonance appearance of multilayered ringlike lesions of demyelination. This disease is extremely rare in children. We present the clinical data, radiological appearance, and development of lesions in eight children. MethodsWe analyzed the clinical information of eight patients diagnosed between 2012 and 2020. Magnetic resonance brain and spinal cord examinations with contrast medium administration were performed using a 1.5-T scanner. ResultsAll patients presented at least one typical Baló lesion on brain imaging. Four patients additionally had typical multiple sclerosis plaques. All primary Baló lesions had a characteristic appearance of concentric hyperintense rings on T2-weighted imaging and were round or ovoid. Cerebrospinal fluid analysis was performed in all patients. Oligoclonal bands were present in seven patients, and four of them had multiple sclerosis plaques on baseline brain magnetic resonance imaging. ConclusionBaló concentric sclerosis in children is characterized by acute and severe onset with hemiparesis as a predominant symptom. The size, contrast enhancement, and restricted diffusion depend on the phase of the disease.

Torsional Nystagmus and Oscillopsia as Initial Presentation of Balo's Concentric Sclerosis.

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New Onset Nystagmus in a Patient with Multiple Sclerosis.

Case PresentationA 50-year-old male with a history of multiple sclerosis with dizziness and nystagmus presented to the emergency department. On physical exam, nystagmus was noted. Computed tomography of the head without contrast was obtained showing a low density in the left frontal lobe. During admission, magnetic resonance imaging (MRI) findings were consistent with Balò’s concentric sclerosis.DiscussionBalò’s concentric sclerosis is a rare, inflammatory demyelinating disease, often considered to be an infrequent variant of multiple sclerosis with alternating rings of healthy myelin and demyelination leading to pathognomonic findings of concentric lamella on T2 or contrast-enhanced T1 MRI imaging.

Successful Management of Natalizumab-Associated Primary Central Nervous System Lymphoma through Autologous Stem Cell Transplant

Natalizumab is used as a second-line treatment for multiple sclerosis (MS). Some reports have linked natalizumab to primary central nervous system lymphoma (PCNSL), although few have described its management. A 45-year-old woman with Balo’s Concentric Sclerosis presented dizziness, vertigo accompanied by dysarthria, weakness on the left side and blurred vision to the right eye after the fourth dose of natalizumab. Magnetic resonance imaging (MRI) and a brain biopsy confirmed the diagnosis of PCNSL. The patient received modified PCNSL chemotherapy (MATRix protocol) followed by high-dose chemotherapy (HDC) supported by an autologous hematopoietic stem cell transplant (ASCT) as a consolidation therapy. Thirty months later, she is still in complete remission of her PCNSL and MS. In this case, whole brain radiotherapy was excluded because it may be associated with an increased risk of neurotoxicity in MS. ASCT was preferred because it has been shown to prevent disability progression in less advanced MS stages. Our patient is the second to receive an ASCT in this context and this option of treatment should be the preferred if the patient is eligible.

Heterogeneity of Bal\xf3\u2019s concentric sclerosis: a study of eight cases with different therapeutic concepts

BackgroundBaló’s Concentric Sclerosis (BCS) is a rare heterogeneous demyelinating disease with a variety of phenotypes on Magnetic Resonance Imaging (MRI). Existing literature lacks data especially on the therapeutic approach of the disease which we intended to elucidate by means of suggesting a new possible BCS classification and introducing different therapeutic concepts based on each BCS-subgroup characteristics.MethodsWe present a retrospective study of eight treated patients with BCS-type lesions, emphasizing on MRI characteristics and differences on therapeutic maneuvers.ResultsData analysis showed: at disease onset the BCS-type lesion was tumefactive (size ≥2 cm) in 6 patients, with a mean size of 2.7 cm (± 0.80 SD); a coexistence of MS-like plaques on brain MRI was identified in 7 patients of our cohort. The mean age was 26.3 years (±7.3 SD) at disease onset and the mean follow-up period was 56.8 months (range 9–132 months). According to radiological characteristics and response to therapies, we further categorized them into 3 subgroups: a) Group-1; BCS with or without coexisting nonspecific white matter lesions; poor response to intravenous methylprednisolone (IVMP); treated with high doses of immunosuppressive agents (4 patients), b) Group-2; BCS with typical MS lesions; good response to IVMP; treated with MS-disease modifying therapies (2 patients), c) Group-3; BCS with typical MS lesions; poor response to IVMP; treated with rituximab (2 patients).ConclusionsOur study introduces a new insight regarding the categorization of BCS into three subgroups depending on radiological features at onset and during the course of the disease, in combination with the response to different immunotherapies. Immunosuppressive agents such as cyclophosphamide are usually effective in BCS. However, therapeutic alternatives like anti-CD20 monoclonal antibodies or more classical disease-modifying MS therapies can be considered when BCS has also mixed lesions similar to MS. Future studies with a larger sample size are necessary to further establish these findings, thus leading to better treatment algorithms and improved clinical outcomes.

Magnetic resonance imaging of Baló’s concentric sclerosis: Literature review and presentation of two focused cases

AbstractThe aim of this study was to describe two cases of Baló’s concentric sclerosis, and to review the state‐of‐the‐art literature. This dissertation is the result of a critical analysis matching the literature and our professional experience. Data were synthesized into a narrative review. BCS is often referred to as a variant of multiple sclerosis (MS). It is still unclear whether BCS is an acute variant of MS or a distinct entity that happens to coexist with MS. BCS and MS‐like lesions might be present at the same time. BCS lesions are characterized by a large concentric “onion‐like” shape on MRI T2‐weighted images composed of alternating hypointense and hyperintense layers. On contrast‐enhanced T1‐weighted images, BCS active lesions usually show an enhancing and non‐enhancing pattern. The advancing edge of demyelination could be represented by peripheral restricted diffusion and contrast enhancement. Baló’s lesions is mainly found in the supratentorial white matter; however; the cerebellum, the brainstem and the spinal cord might be affected as well. The present two cases both showed onion‐like lesions; case 1 showed typical BCS features, whereas case 2 was atypical and could be classified as probably BCS or as a BCS‐like lesion in the course of MS. It is important for radiologists to be able to recognize this type of lesion and to cooperate with clinicians to help them carry out earlier diagnosis and treatment, determining a better clinical outcome for patients affected by BCS, even without histological confirmation, which is still considered the gold standard.

Distinct microglial and macrophage distribution patterns in the concentric and lamellar lesions in Baló's disease and neuromyelitis optica spectrum disorders.

TMEM119 and purinergic receptor P2Y12 (P2RY12), which are not expressed by recruited peripheral blood macrophages, are proposed to discriminate microglia from macrophages. Therefore, we investigated the distribution patterns of microglia and macrophages in 10 concentric lesions from four autopsied Baló's disease cases and one neuromyelitis optica spectrum disorder (NMOSD) case, using quantitative immunohistochemistry for the markers TMEM119, P2RY12, CD68, CD163 and GLUT5. Three cases with Baló's disease had distal oligodendrogliopathy (DO) showing preferential loss of myelin-associated glycoprotein and early active demyelination in the outermost demyelinating layer (termed DMY-MO). In DMY-MO with DO, TMEM119-positive activated microglia expressing upregulated GLUT5 but markedly downregulated P2RY12 were significantly increased. These activated microglia expressed inducible nitric oxide synthase. Oligodendrocytes and their precursors showed apoptotic-like nuclear condensation in DMY-MO. TMEM119-negative and CD68/CD163-positive macrophages were distributed throughout the lesion center of DMY-MO with DO and these cells demonstrated foamy morphology only in the inner portion but not in the outer portion. In concentric demyelinating lesions from another Baló's case and lamellar demyelinating lesions in an NMOSD case, which had late active demyelination without DO, the densities of TMEM119-, GLUT5- and P2RY12-positive microglia with ramified morphology were significantly increased in myelinated layers but not in demyelinating layers. In particular, in the NMOSD case, TMEM119-positive microglia were confined to the outer portion of the myelinated layers. CD68-positive macrophages with foamy morphology also expressing CD163 accumulated in myelinated as well as in demyelinated layers. These findings suggest that activated microglia expressing TMEM119 and GLUT5, but not P2RY12, are associated with apoptosis of oligodendrocytes in the leading edge of Baló's concentric lesions with DO, whereas TMEM119-, GLUT5- and P2RY12-positive microglia with ramified morphology are associated with myelin preservation in concentric lesions without DO in Baló's disease and NMOSD. These two types of microglia appear to play distinct roles in the formation of concentric lesions.

TSPO PET With 18F-GE-180 to Differentiate Variants of Multiple Sclerosis: Relapsing-Remitting Multiple Sclerosis, Tumefactive Demyelination, and Baló's Concentric Sclerosis.

PET targeting the translocator protein (TSPO) expression is an interesting approach to detect neuroinflammation, as TSPO is upregulated in activated macrophages and microglia. Considering the variable pathophysiology of multiple sclerosis (MS) variants, we compare TSPO PET using F-GE-180 in 3 different demyelinating diseases of the central nervous system: relapsing-remitting MS, tumefactive MS, and Baló's concentric sclerosis. Visualization of neuroinflammation and its PET patterns in addition to MRI may contribute to accurate distinction and monitoring of central nervous system demyelination.

From Baló’s concentric sclerosis to multiple sclerosis: a series of 6 patients

IntroductionBaló’s concentric sclerosis (BCS) is a rare CNS disorder characterized by alternating bands of demyelination on MRI. One of the main issues is its relationship with multiple sclerosis (MS). ObjectivesTo describe 6 BCS patients. To review the risk of developing MS in BCS patients. MethodsWe retrospectively recorded clinical and radiological findings of 6 BCS patients and performed a review of the literature. ResultsSix patients (5 women) with a mean age of 25 years old were included. Main symptoms were hemiparesis/hemihypoesthesia. On MRI, two patients had a single BCS lesion and four had additional MS-like lesions. Alternating bands were usually more visible on DWI. A patient had reduced central perfusion and SWI hypointensity suggestive of a central vein. Oligoclonal bands were identified in 5/6 patients. After 7 years of follow-up, all patients achieved MS criteria with mild disability (mean EDSS 1.75; 0–4). Our literature review included 65 BCS patients from 30 studies: although CSF oligoclonal bands and the presence of additional MS lesions were associated with subsequent relapses, this was not significant. Discussion/conclusionOur series allows a detailed MRI description in BCS and gives a new insight into BCS evolution and its strong relationship with MS.

A Rare Case of Balos Concentric Sclerosis (BCS) in a Patient with Multiple Sclerosis (MS) (2241)

A Rare Case of Balos Concentric Sclerosis (BCS) in a Patient with Multiple Sclerosis (MS) (2241)

Imaging of Fulminant Demyelinating Disorders of the Central Nervous System.

We aim to review the imaging appearance of fulminant demyelinating disorders of central nervous system that have different pathological features, clinical course, clinical features, and imaging findings different from classic multiple sclerosis. Routine magnetic resonance imaging (MRI) can help in accurate localization of the lesions, detection of associated lesions, and monitoring of these patients. Advanced MRI combined with routine MRI can aid in differentiation fulminant demyelinating lesions from simulating malignancy. Tumefactive demyelination lesions are located in supratentorial white matter mainly frontal and parietal regions with incomplete rim enhancement. Baló concentric sclerosis shows characteristic concentric onion skin appearance. Schilder disease is subacute or acute demyelinating disorders with one or more lesions commonly involving the centrum semiovale. Marburg disease is the most severe demyelinating disorder with diffuse infiltrative lesions and massive edema involving both the cerebral hemisphere and brain stem.

Does established vascular kidney disease exist?

Does established vascular kidney disease exist?

Antibody signatures in patients with histopathologically defined multiple sclerosis patterns

Early active multiple sclerosis (MS) lesions can be classified histologically into three main immunopathological patterns of demyelination (patterns I–III), which suggest pathogenic heterogeneity and may predict therapy response. Patterns I and II show signs of immune-mediated demyelination, but only pattern II is associated with antibody/complement deposition. In pattern III lesions, which include Baló’s concentric sclerosis, primary oligodendrocyte damage was proposed. Serum antibody reactivities could reflect disease pathogenesis and thus distinguish histopathologically defined MS patterns. We established a customized microarray with more than 700 peptides that represent human and viral antigens potentially relevant for inflammatory demyelinating CNS diseases, and tested sera from 66 patients (pattern I n = 12; II n = 29; III n = 25, including 8 with Baló’s), healthy controls, patients with Sjögren’s syndrome and stroke patients. Cell-based assays were performed for aquaporin 1 (AQP1) and AQP4 antibody detection. No single peptide showed differential binding among study cohorts. Because antibodies can react with different peptides from one protein, we also analyzed groups of peptides. Patients with pattern II showed significantly higher reactivities to Nogo-A peptides as compared to patterns I (p = 0.02) and III (p = 0.02). Pattern III patients showed higher reactivities to AQP1 (compared to pattern I p = 0.002, pattern II p = 0.001) and varicella zoster virus (VZV, compared to pattern II p = 0.05). In patients with Baló’s, AQP1 reactivity was also significantly higher compared to patients without Baló’s (p = 0.04), and the former revealed distinct antibody signatures. Histologically, Baló’s patients showed loss of AQP1 and AQP4 in demyelinating lesions, but no antibodies binding conformational AQP1 or AQP4 were detected. In summary, higher reactivities to Nogo-A peptides in pattern II patients could be relevant for enhanced axonal repair and remyelination. Higher reactivities to AQP1 peptides in pattern III patients and its subgroup of Baló’s patients possibly reflect astrocytic damage. Finally, latent VZV infection may cause peripheral immune activation.

Global boundedness and stability for a chemotaxis model of Boló's concentric sclerosis.

Baló's concentric sclerosis (BCS) is considered a variant of inflammatory demyelinating disease closely related to multiple sclerosis characterized by a discrete concentrically layered lesion in the cerebal white matter. Khonsari and Calvez (Plos ONE. 2(2007)) proposed a parabolic-elliptic-ODE chemotaxis model for BCS which describes the evolution of the densities of activated macrophages, cytokine and apoptotic oligodendrocytes. Because "classically activated" M1 microglia can produce cytotoxicity, we introduce a linear production term from the activated microglia in the ODE for pro-inflammatory cytotoxic. For the new BCS chemotaxis model, we first investigate the uniform boundedness and global existence of classical solutions, and then get a range of the chemosensitive rate χ where the unique positive equilibrium point is exponentially asymptotically stable.

Balo’s concentric sclerosis: a case report

Balo’s concentric sclerosis is a rare variant of multiple sclerosis which is characterized by lesions consisting rings of demyelination alternating with areas of relatively preserved myelin. These pathological changes are reflected by characteristic magnetic resonance imaging findings. We present the imaging findings of a case of BCS who presented with an acute neurological disturbance, showed a dramatical recovery following corticosteroid therapy, and remained free of relapse for more than 1 year. Although previously considered as a fulminant and fatal disease, characteristic MRI findings of Balo’s concentric sclerosis enable earlier diagnosis and treatment, and better prognosis.

Pseudotumoral demyelinating lesions: diagnostic approach and long-term outcome.

To review the clinical findings, differential diagnosis, treatment and outcome of pseudotumoral demyelinating lesions including tumefactive demyelination and Baló's concentric sclerosis. MRI findings, such as dynamic restricted diffusion changes at the edge of pseudotumoral lesions help to discriminate atypical demyelination from key differential diagnoses, and together with histopathological data, indicate that tissue hypoxia may be important aetiologically. CT-PET imaging can help to distinguish pseudotumoral lesions from high-grade tumours. Although most patients with pseudotumoral lesions have or later develop multiple sclerosis, a proportion will experience a monophasic course or be diagnosed with neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination or acute disseminated encephalomyelitis (ADEM). Many patients with pseudotumoral demyelinating lesions have a favourable prognosis. Not all patients with pseudotumoral lesions require a brain biopsy but close follow-up of biopsied and nonbiopsied lesions is indicated once a diagnosis is established. Testing for AQP4-IgG and MOG-IgG is recommended when a pseudotumoral demyelinating lesion is identified. In the absence of large, prospective studies, it seems reasonable that patients with pseudotumoral lesions who fulfil multiple sclerosis diagnostic criteria are treated with multiple sclerosis therapies.

P46-T Unexpected electrophysiological findings in a boy with Balo concentric sclerosis

Background Balo concentric sclerosis is a rare form of multiple sclerosis (MS) characterized by tumefactive demyelination. Clinical presentation is usually polysymptomatic, however motor and sensory symptoms are the most common. Tetany is rarely found in patients with It can manifest by tingling and muscle cramps. Once suspected EMG tetany test should be performed. Material and Methods A 15 year old boy with hand paresis, paresthesias and visual disturbances was admitted to the Chair of Pediatric and Adolescent Neurology Jagiellonian University Collegium Medicum in Cracow in August 2018. Results Head MRI revealed concentric demyelination. Result of lumbar puncture was positive for oligoclonal bands. Infection agents were excluded. Additionally the boy suffered from recurrent syncopes. Video-EEG test did not reveal abnormalities. However during hyperventilation he experienced paresthesias in the right upper limb. During hospitalization paresthesias reappeared and were associated with involuntary finger flexion in right arm. EMG tetany test was performed giving strongly positive electrophysiological and clinical result. Electrolytes levels were within normal limits. PTH level was normal and vitamin D level low borderline. The boy was diagnosed with Balo concentric sclerosis and immunomodulating treatment has been introduced based on dimethyl fumarate. Six month observation has revealed good clinical outcome and treatment tolerance. Additionally vitamin D3 supplementation has been order. No signs of tetany has been observed since last hospitalization. Conclusions We report an unexpected result of EMG tetany test in a boy with Balo concentric sclerosis, probably due to low borderline vitamin D3 concentration and additional emotional stress.

Elevated lipid peaks during the recovery phase of Baló's concentric sclerosis: A case report

Elevated lipid peaks during the recovery phase of Baló's concentric sclerosis: A case report

Myelinoclastic diffuse sclerosis (Schilder\u2019s disease) is immunologically distinct from multiple sclerosis: results from retrospective analysis of 92 lumbar punctures

BackgroundMyelinoclastic diffuse sclerosis (MDS; also termed Schilder’s disease) is a rare inflammatory demyelinating disorder of the central nervous system characterised by demyelination of vast areas of the white matter. It is unclear whether MDS is a variant of multiple sclerosis (MS) or a disease entity in its own right.ObjectiveTo compare the cerebrospinal fluid (CSF) features of MDS with those of MS.MethodsRetrospective analysis of the CSF profile of all patients with MDS reported in the medical literature between 1960 and 2018.ResultsThe most striking finding was a substantial lack of oligoclonal bands (OCBs) in MDS, which were absent in at least 77% (30/39) of all lumbar punctures (LP) in the total cohort and in 86% in the subgroup of patients with normal very long-chain fatty acid serum ratios (VLCFA). Almost all cases published in the past 15 years were negative for OCBs. These findings are in contrast to MS, in which OCBs are present in up to 98% of cases (p < 0.00001 when compared with reference works in MS; both in adult and in pediatric patients). CSF pleocytosis was absent in at least 79% (46/58) of all LP (p < 0.0001 vs. MS) and in 92% (24/26) of LPs in the VLCFA-tested subgroup. CSF total protein levels were elevated in 56% of all LPs (p < 0.0001 vs. MS) and in 63% of LPs in the VLCFA-tested subgroup and were often higher than in typical MS (> 100 mg/dL in 13/22; up to 220 mg/dL). EBV serum antibodies, which are present in virtually all patients with MS, and the so-called MRZ (measles/rubella/zoster) reaction, a highly specific marker of MS, were absent in all of the few patients tested. In addition, we discuss further differences between MS and MDS, taking into account also Schilder’s original comprehensive case description from 1912.ConclusionIn the majority of patients diagnosed with MDS, CSF features differ significantly from those typically found in MS and are more similar to those previously reported in patients with myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-positive encephalomyelitis, aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders or Baló’s concentric sclerosis. Our data suggest that MDS and MS are immunopathologically distinct entities in the majority of cases.