Pediatric tumefactive multiple sclerosis case (with baló-like lesions), diagnostic and treatment challenges.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, rare during childhood. MS variations, like tumefactive MS and Balo concentric sclerosis, constitute puzzling to treat diagnostic dilemmas for pediatric patients. Differential diagnosis, mainly from brain tumors, is an absolute necessity. In addition, apart from treating acute attacks, immunomodulatory alternatives are limited. CASE: We present a 12.5-year-old boy diagnosed, 5 years ago, with tumefactive relapsing-remitting MS, with severe recurrent clinical attacks. Definite diagnosis of demyelination was achieved via combined brain imaging including magnetic resonance (MR) imaging, MR spectroscopy and computed tomography, avoiding brain biopsy. Acute attacks showed satisfactory response to aggressive treatment choices, like plasmapheresis and cyclophosphamide, but age-appropriate immunomodulating treatment was available, only 2 years later. Finally, after a last radiological relapse, when he was 10 years old, fingolimod was initiated. He has been clinically and radiologically stable since, presenting an excellent treatment tolerance.

Baló's concentric sclerosis - A rare entity within the spectrum of demyelinating diseases.

Baló's concentric sclerosis (BCS) is a rare, inflammatory demyelinating disease of the central nervous system (CNS). Historically, BCS was thought to be uniformly fatal and diagnosis was based on postmortem findings. With advances in modern neuroimaging, BCS is currently defined by the presence of concentric layered patterns composed of alternating rings of varying intensity. They are best appreciated on gadolinium-enhanced T1-weighted sequences and predominantly occur in the supratentorial cerebral white matter with sparing of cortical U-fibers. The lamellar pattern of the lesions likely reflects bands of demyelination and relative myelin preservation with minimal axonal loss. While BCS falls within the spectrum of atypical demyelinating diseases, there is ongoing debate over whether BCS is a phenotypical variant of multiple sclerosis (MS) or a separate entity. Corticosteroids comprise first-line therapy but there is ongoing controversy regarding appropriate maintenance therapy. First-line MS disease-modifying therapies such as interferon beta-1a are appropriate for patients who fulfill diagnostic criteria for relapsing-remitting MS. Fingolimod should likely be avoided as Baló-like lesions have been reported during its administration or after withdrawal. Monoclonal antibodies such as natalizumab and rituximab are potentially effective at reducing BCS relapses, but alemtuzumab may be relatively ineffective because humoral immunity does not play a central role in BCS pathogenesis.

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

OBJECTIVE: To describe clinical, radiologic, and pathologic features of Baló concentric sclerosis (BCS) and assess overlap between BCS and other CNS inflammatory demyelinating diseases. METHODS: Retrospective review of BCS cases from US and Australian tertiary care centers. RESULTS: 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). CONCLUSIONS: BCS may be a distinct subtype of multiple sclerosis characterized by pattern III immunopathology.

Heterogeneity of Baló's concentric sclerosis: a study of eight cases with different therapeutic concepts.

BACKGROUND: Baló'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. METHODS: We present a retrospective study of eight treated patients with BCS-type lesions, emphasizing on MRI characteristics and differences on therapeutic maneuvers. RESULTS: Data 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). CONCLUSIONS: Our 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.

Long-term Outcome of Schilder Disease Treated With Interferon-ß.

Schilder disease, also termed diffuse myelinoclastic sclerosis, is characterized by a large demyelinating lesion involving 1 or both sides of the centrum semiovale of the cerebral hemispheres. It often presents with tumorlike features and poses a diagnostic challenge. Schilder disease can be monophasic or relapsing, and disease-modifying therapy for the latter scenario is largely empirical. Here, we report a 14-year-old girl with relapsing Schilder disease within 1 year after disease onset. She has been followed-up for nearly 10 years and remains in sustained remission ever since interferon-ß therapy was prescribed after the second attack. In this case study, it is suggested that interferon-ß may induce long-term remission in relapsing Schilder disease and is therefore worth considering in this regard.

Recurrent schilder's disease.

Schilder's disease is a rare and aggressive central nervous system demyelinating disorder that is typically monophasic and steroid responsive. Here, we present an unusual case of a teenager with Schilder's disease who was treated with corticosteroids and had a clinical and radiographic recurrence nearly one year after the initial presentation.

Esclerosis concéntrica de Balo: una presentación que simula un ictus isquémico / Balo concentric sclerosis: a presentation mimicking ischaemic stroke

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Early diagnosis of Balo's concentric sclerosis by diffusion tensor tractography: a case report and literature review.

Balo concentric sclerosis is an infrequent variant of a demyelinating disease related to multiple sclerosis, initially thought to have an acute presentation and a fatal outcome. Recent studies have reported non-fatal forms of Balo concentric sclerosis, focusing on the importance of early diagnosis using magnetic resonance imaging (MRI), along with spectroscopy and diffusion/perfusion sequences. Recently, we have been able to draw a three-dimensional image of a specific bundle of fibers by means of a diffusion tensor technique of the magnetic resonance imaging tractography (t-MRI). We report the case of a young woman presenting with acute and progressive focal neurological symptoms, including right body paresis, whose diagnosis was suggested by MRI and confirmed by pathology to be Balo concentric sclerosis. She was treated with boluses of methylprednisolone, achieving full neurological remission one year after admission. This is, to our knowledge, the first report describing the use of t-MRI for diagnosing BCS. We consider that t-MRI will allow, in a near future, early diagnosis of the disease, its prompt treatment, and establishing new classification criteria. This case confirms the existence of benign forms of Balo concentric sclerosis with a good response to steroid therapy, where functional recovery is possible.

La esclerosis concéntrica de Baló es una variante infrecuente de enfermedad desmielinizante relacionada con la esclerosis múltiple, inicialmente considerada de progresión fatal. En estudios recientes se reportan variantes no fatales de esclerosis concéntrica de Baló en los que se enfatiza la importancia del diagnóstico por medio de la imagen por resonancia magnética, utilizando además la espectroscopia y las secuencias de difusión y perfusión. En los últimos años se ha logrado reproducir la imagen tridimensional de un fascículo en particular y observar la presencia de lesiones por medio de la tractografía por imagen por resonancia magnética mediante la técnica de tensor de difusión. Presentamos el caso de una mujer joven con síntomas neurológicos focales agudos, incluyendo paresia de extremidades derechas, cuyo diagnóstico por biopsia fue de esclerosis concéntrica de Baló, confirmando el resultado de los estudios de imagen. La paciente recibió tratamiento con bolos de metilprednisolona, obteniendo remisión clínica completa a largo plazo. A nuestro entender, este es el primer reporte que describe los hallazgos de la esclerosis concéntrica de Baló utilizando la técnica de tensor de difusión. Consideramos que dicha técnica permitirá en el futuro la detección temprana de la enfermedad, su tratamiento oportuno y permitirá establecer nuevos criterios de clasificación y estratificación. Este caso demuestra la existencia de variantes benignas de esclerosis concéntrica de Baló, que tienen buena respuesta a la terapia con glucocorticoides y donde se logra la recuperación funcional.

"Clues on Balo's concentric sclerosis evolution from serial analysis of ADC values".

Balò's sclerosis is considered a rare variant of multiple sclerosis characterized by demyelination with concentric rings. Advanced magnetic resonance studies allow nowadays early diagnosis and prompt treatment. However, the pathophysiology of lesion evolution is still matter of debate, as detailed in our literature review. Based on a clear-cut Balò's lesion analysis, we describe early changes in DWI and ADC values within the different layers, favoring the concept of a centrifugal growth.

Balò's concentric sclerosis: still to be considered as a variant of multiple sclerosis?

Balò's concentric sclerosis (BCS) is considered a rare demyelinating disease and regarded as an aggressive variant of multiple sclerosis (MS). We describe three cases (one male and two females) with neuroimaging features suggestive of BCS and heterogeneous symptoms, with benign long-term clinical course upon treatment with natalizumab and fingolimod. Neurological examination, blood and cerebrospinal fluid analyses, brain and spinal cord magnetic resonance imaging (MRI) and brain proton magnetic resonance spectroscopy were performed. At onset, patient #1 showed predominant cognitive impairment with consciousness disturbances; patient #2 presented with left hemiparesis; patient #3 demonstrated hesitance in speech and in written word production, along with right central facial palsy. All patients showed the typical MRI changes associated with BCS, such as concentric rings or a whorled appearance on T2-weighted and contrast-enhanced T1-weighted images. They were treated with high dosage i.v. steroid with clinical improvement and followed-up for 3 years with different clinical course. Two patients fulfilled the revised McDonald criteria for MS and received preventive therapy, natalizumab and fingolimod, respectively, whereas the third patient is still stable without clinical and radiological evolution. All of them did not have new exacerbations or MRI lesions over 2-4 year follow-up. Our descriptions demonstrate the heterogeneity of clinical presentation of BCS. Moreover, these case reports suggest that BCS may neither be rapidly progressive nor fatal and may be considered part of the MS spectrum. In line with this hypothesis, current treatments for MS were effective in our patients.

Peripheral late reactivation of a previously typical monofocal Baló's concentric sclerosis lesion.

We report a 41-year-old woman with rapidly progressive left hemiparesis, revealing an inflammatory reactivation of a previously known parietal Baló's concentric sclerosis lesion. The first attack occurred five years before. After a slow recovery following high-dose steroid infusions the patient stabilized. Because of recurrent ataxia and left hemiparesis a new magnetic resonance imaging was performed showing an extension of the initial lesion with a peripheral gadolinium enhancement on T1-weighted images. Such a reactivation pattern of an isolated Baló's concentric sclerosis lesion, occurring some years later, is described for the first time.

Combination treatment of interferon ß-1b and warfarin for a patient with Baló's concentric sclerosis and antiphospholipid syndrome.

BACKGROUND: Baló's concentric sclerosis (BCS), a rare variant of multiple sclerosis (MS), as the initial presentation of antiphospholipid syndrome (APS) is unusual. The pathogenic role of antiphospholipid antibodies in the development of MS remains unknown. Anticoagulant therapy might be used in patients with MS and APS for prevention against the relapse of MS. CASE REPORT: We present a 27-year-old man diagnosed as BCS with APS. Initially, after corticosteroid therapy, he exhibited a complete recovery. During follow-up, his Baló-like lesion dissolved over time but transformed into other asymptomatic MS-like lesions. He also had persistently elevated anticardiolipin IgG levels. The patient was, therefore, on a combined therapy of interferon ß-1b and an anticoagulant agent. No new brain lesions were found on 2 occasional head magnetic resonance imaging studies at 1 year follow-up. CONCLUSIONS: To prevent further MS relapse and thrombotic complications of APS, a combined therapy of interferon ß-1b and an anticoagulant agent can be an important strategy in treating patients with both BCS and APS.

First use of alemtuzumab in Balo's concentric sclerosis: a case report.

Balo's concentric sclerosis (BCS) is a rare demyelinating disorder of the central nervous system. The humanised monoclonal antibody alemtuzumab has shown efficacy in another demyelinating disorder, relapsing-remitting multiple sclerosis. We aimed to explore its efficacy in treatment-refractory BCS. A 52-year-old male with radiologically confirmed progressive BCS resistant to steroids, plasmapharesis and cyclophosphamide was administered a standard protocol of alemtuzumab. Treatment failed to slow his decline; he died 6 months after administration. Why alemtuzumab induced no clinical or radiological impact may be multifactorial. We review the evidence directing BCS therapy and propose the next steps for exploring this potentially fatal condition.