Concentric Sclerosis Research Articles

Technology Insight: can neuroimaging provide insights into the role of ischemia in Baló's concentric sclerosis?

Baló's concentric sclerosis (BCS) has long been considered to be a variant of multiple sclerosis. Although BCS was initially described over 100 years ago, relatively few antemortem cases have been identified, and the exact pathogenesis remains unknown. Inflammatory protective ischemic preconditioning has recently been suggested as a mechanism by which the typical concentric rings of the BCS lesion are formed. Advanced neuroimaging can provide important in vivo markers of disease progression that can assist in the diagnosis and management of patients with BCS. In this Review, we discuss evidence from longitudinal neuroimaging studies that supports the role of ischemic preconditioning in BCS.

Baló's concentric sclerosis presenting as a stroke-like syndrome

A 37-year-old woman without important previous medical history presented to an emergency room with acute onset of left-sided weakness and numbness. Examination revealed left-sided hemiparesis (in the arm greater than in the leg) and hypoesthesia. Routine laboratory testing, lumbar puncture, dynamic susceptibility contrast perfusion study, longitudinal brain MRI, and magnetic resonance spectroscopy were performed. Balós concentric sclerosis. Intravenous methylprednisolone followed by oral steroid taper.

Treatment of pediatric multiple sclerosis and variants

Studies in adult patients with multiple sclerosis (MS) suggest significant benefit of early treatment initiation. However, there are no approved therapies for children and adolescents with MS. For adult MS, tolerability and efficacy of several immunomodulatory and immunosuppressive drugs have been demonstrated. Guidelines for the use of these MS therapies in children do not exist. Several small cohort studies of the safety and tolerability of disease-modifying therapies (DMT) in children and adolescents with MS have been recently reported. The side effects of interferon beta (IFNB) and glatiramer acetate (GA) appear to be similar to those reported by adults. The long-term tolerability and safety have yet to be established and efficacy data have yet to be studied. In view of the potential for significant long-term physical and cognitive disability in children with MS, and recent evidence that initiation of immunomodulatory therapy early in the course of MS improves long-term prognosis, an increasing number of children and adolescents with MS are being offered the DMT approved for adults. This review summarizes current knowledge of DMT in pediatric MS and experience in several centers treating pediatric MS and MS variants such as neuromyelitis optica or Devic disease, Balo concentric sclerosis, Marburg acute MS, and Schilder disease (myelinoclastic diffuse sclerosis). Finally, an overview of symptomatic MS therapies and experiences with these treatments in pediatric patients is provided.

Apparent diffusion coefficient changes and lesion evolution in Balo's type demyelination—correlation with histopathology

Balo's concentric sclerosis is a variant of multiple sclerosis (MS) that presents with concentric rings on T1- and T2-weighted magnetic resonance imaging (MRI) showing various patterns of contrast enhancement.1–3 Originally described by Marburg in 19064 as a monophasic fatal disease, it was Balo that first reported the characteristic concentric pattern.5

Endogenous lipoid pneumonia associated with primary sclerosing cholangitis

In July, 2005, a 63-year-old non-smoking white woman was admitted to hospital with a 3-month history of nonproductive cough, slightly febrile body temperature, and right upper quadrant abdominal pain. The patient had no history of previous medical problems. On admission, physical examination was normal. Blood test results showed a cholestatic pattern with increased γ-glutamyl transferase (γGT) of 321 U/L and alkaline phosphatase of 204 IU/L. Total serum cholesterol concentration was 7·6 mmol/L. Despite 3 weeks’ antibiotic therapy before admission, C-reactive protein was high at 180 mg/L. Screening for autoantibodies (antinuclear, anti mitochondrial, and anti cytoplasmic antibodies) was negative. Chest radiography on admission showed no abnormalities; high-resolution CT of the lungs showed consolidation of the lingula and the middle lobe region (fi gure A). Fibreoptic bronchoscopy was done; cytological examination of the lavage-fl uid showed predominantly foam cell macrophages (fi gure B) containing large fatty vesicles, and lipid droplets were detected on Sudan III staining, characteristic for lipoid pneumonia. Histological examination of the subsequent transbronchial lung biopsy sample showed mild interstitial infl ammation, without signs of malignancy or other interstitial lung disease. The patient denied mineral oil ingestion or nasal drop misuse. She was therefore diagnosed with endogenous lipoid pneumonia due to hypercholesterolaemia. To clarify the cause of the cholestasis, magnetic resonance cholangio-pancreaticography was done, which showed a narrowed hepatic bile duct system together with vanishing of the small bile ducts—characteristic for primary sclerosing cholangitis. Liver biopsy confi rmed the diagnosis by showing concentric sclerosis around bile ducts with little infl ammatory infi ltration, periductal fi brosis, multifocal strictures, and dilatations. We started our patient on 15 mg/kg ursodeoxycholic acid and 40 mg atorvastatin daily. Her condition improved substantially, and she became completely asymptomatic after 6 weeks. Total serum cholesterol dropped to 4·6 mmol/L and γGT to 100 U/L; alkaline phosphatase and C-reactive protein concentration returned to normal values. CT scan showed marked improvement with complete resolution of lung infi ltration after 6 weeks of treatment. Lipoid pneumonia may be classifi ed as exogenous or endogenous. Endogenous lipoid pneumonia usually develops when lipids that normally are found in the lung tissue escape from destroyed alveolar cell wall distal to an obstructing, usually malignant, airway lesion or from lung tissue damaged by a suppurative process. Less commonly, endogenous lipids appear in the lung with fat embolism or thromboembolism, Wegener’s granulomatosis, pulmonary alveolar proteinosis, or lipid storage diseases. Hypercholesterolaemia is common in patients with primary sclerosing cholangitis and can lead to an accumulation of cholesterol in diff erent tissues and can be the underlying cause of an ongoing infl ammatory process. The lungs are actively involved in lipid metabolism, and macrophages help to clear lipids from the lungs. The mechanisms involved in lipoid pneumonia are unclear but may involve an infl ammatory response that is linked to increased lipid uptake by alveolar macrophages. The activity of the disease is not necessarily mirrored by the serum total cholesterol concentration, which might explain the discrepancy of the severity of disease in our patient and the relatively moderate elevation of the serum cholesterol concentration. Treatment of endogenous lipiod pneumonia is not standardised. Successful treatment with total lung lavage or with systemic steroids has been reported, proposing an underlying autoimmune phenomenon of the disease (supported by our case). Our patient was successfully treated by lowering her serum cholesterol concentration and thereby terminating the underlying cause of infl ammation, strongly supporting the link between endogenous lipoid pneumonia and pathogenic role of serum lipids.

Idiopathic inflammatory-demyelinating diseases of the central nervous system

Idiopathic inflammatory-demyelinating diseases (IIDDs) include a broad spectrum of central nervous system disorders that can usually be differentiated on the basis of clinical, imaging, laboratory and pathological findings. However, there can be a considerable overlap between at least some of these disorders, leading to misdiagnoses or diagnostic uncertainty. The relapsing-remitting and secondary progressive forms of multiple sclerosis (MS) are the most common IIDDs. Other MS phenotypes include those with a progressive course from onset (primary progressive and progressive relapsing) or with a benign course continuing for years after onset (benign MS). Uncommon forms of IIDDs can be classified clinically into: (1) fulminant or acute IIDDs, such as the Marburg variant of MS, Baló's concentric sclerosis, Schilder's disease, and acute disseminated encephalomyelitis; (2) monosymptomatic IIDDs, such as those involving the spinal cord (transverse myelitis), optic nerve (optic neuritis) or brainstem and cerebellum; and (3) IIDDs with a restricted topographical distribution, including Devic's neuromyelitis optica, recurrent optic neuritis and relapsing transverse myelitis. Other forms of IIDD, which are classified clinically and radiologically as pseudotumoral, can have different forms of presentation and clinical courses. Although some of these uncommon IIDDs are variants of MS, others probably correspond to different entities. MR imaging of the brain and spine is the imaging technique of choice for diagnosing these disorders, and together with the clinical and laboratory findings can accurately classify them. Precise classification of these disorders may have relevant prognostic and treatment implications, and might be helpful in distinguishing them from tumoral or infectious lesions, avoiding unnecessary aggressive diagnostic or therapeutic procedures.

The origins of concentric demyelination: self-organization in the human brain.

Baló's concentric sclerosis is a rare atypical form of multiple sclerosis characterized by striking concentric demyelination patterns. We propose a robust mathematical model for Baló's sclerosis, sharing common molecular and cellular mechanisms with multiple sclerosis. A reconsideration of the analogies between Baló's sclerosis and the Liesegang periodic precipitation phenomenon led us to propose a chemotactic cellular model for this disease. Rings of demyelination appear as a result of self-organization processes, and closely mimic Baló lesions. According to our results, homogeneous and concentric demyelinations may be two different macroscopic outcomes of a single fundamental immune disorder. Furthermore, in chemotactic models, cellular aggressivity appears to play a central role in pattern formation.

Quantitative MRS study of Baló's concentric sclerosis lesions

Baló's concentric sclerosis (BCS) lesions display specific metabolite changes detected by magnetic resonance spectroscopy (MRS). We report on two cases of BCS lesions examined by MRS; the first case was evaluated 36 days after the onset of symptoms, whereas the second case was evaluated 9 days after the onset of symptoms. MRS data were obtained from single voxels located in the lesion and in the contralateral region. Relative to the creatine/phosphocreatine peak, BCS lesions displayed decreases of N-acetyl aspartate and increases of choline, myo-inositol (mI), glutamine/glutamate (Glx), lactate and lipid+macromolecule signals, in agreement with previous reports. In addition, previously unreported decreases of mI (-19% to -29%) and increases of Glx (+55% to +198%) were measured; these could be useful in characterizing BCS lesions.

Diffusion-weighted imaging findings in Balo concentric sclerosis

Balo concentric sclerosis is a rare demyelinating disease. Pathognomonic features have been previously described. Diffusion-wighted imaging findings have not been previously described in Balo concentric sclerosis. We describe the diffusion-weighted imaging findings in a 45-year-old lady with Balo concentric sclerosis. Diffusion-weighted imaging offers insight into the possible pathophysiology of this rare disease.

The lumping and splitting of inflammatory CNS diseases

Immune-mediated CNS disorders include relapsing forms of multiple sclerosis (RRMS), primary progressive MS (PPMS), Balo concentric sclerosis, Marburg disease, transverse myelitis (TM), longitudinally extensive myelitis (LETM), optic neuritis (ON), neuromyelitis optica (NMO), acute disseminated encephalomyelitis (ADEM), and acute hemorrhagic leukoencephalopathy (AHLE). Others should probably be included in this list: postinfectious movement and behavioral disorders, paraneoplastic disorders, stiff person syndrome, and Rasmussen encephalitis—even collagen-vascular disorders such as systemic lupus erythematosus and Sjogren, sarcoidosis, and vasculitis. Each of these disorders has some distinctive spatial, temporal, imaging, biologic, or pathologic feature that separates it from the others,1 but how should we classify and diagnose these disorders? Are they variations of a single theme that warrant lumping together? Or are they distinct disorders, linked only by the presence of abnormal inflammation in the CNS, more appropriately split into individual entities? Equally important, does it really matter? Once we name a specific disorder in a given patient, does that indicate the most appropriate treatment and predict prognosis for that patient? The answer is probably yes on both counts. It is increasingly clear that the risk of recurrence, …

Successful pregnancy of a patient with Balo's concentric sclerosis

Balo's concentric sclerosis is a severe demyelinating disease with poor prognosis. To date, nothing is known about the effects of pregnancy on the course of Balo's disease. We describe here the first successful pregnancy of a patient with Balo's concentric sclerosis. Upon neurological worsenings during pregnancy, our patient was treated with high-dose methylprednisolone and plasma-exchange. Intravenous immunoglobulin and interferon-beta-1a were given postpartum. At the last follow-up visit 2.5 years after the delivery the patient had only minor residual symptoms.

Successful pregnancy of a patient with Balo's concentric sclerosis

Successful pregnancy of a patient with Balo's concentric sclerosis

Establishing preconditions for Baló's concentric sclerosis

Concentric sclerosis is a rare variant of multiple sclerosis, first described by Balo in 1928 (Balo, 1928). It is characterized by the development of alternating bands of demyelinated and myelinated white matter, forming concentric rings or irregular stripes. In an affected patient these lesions are usually multiple but may be admixed with other, typical plaques. Although often a feature of rapidly progressive disease, Balo's sclerosis is not always fatal and can also occur in chronic multiple sclerosis, as has been well demonstrated by the use of MRI (Bolay et al ., 1996; Karaarslan et al ., 2001). The pathogenesis of this histologically striking form of demyelination has long been a puzzle. Although in some cases the bands of myelinated white matter include remyelinated fibres (Moore et al ., 1985), the myelin sheaths within the bands are mostly of normal thickness, indicating that they have been preserved from demyelination rather than being a product of remyelination (Moore et al ., 2001). There is some loss of oligodendrocytes, but much less so in the preserved white matter than in the intervening bands of demyelination. Similarly, mRNA levels for myelin-related proteins are lowest in demyelinated areas, intermediate in the preserved bands, and highest in the normal-appearing white matter away from the lesions (Yao et al ., 1994). In previous studies of multiple sclerosis, Lassman and colleagues found that the oligodendrocytes in some plaques had similar abnormalities to those …

Intérêt de la spectroscopie par résonance magnétique dans la sclérose concentrique de Balo

Balo's concentric sclerosis is a neuropathological type of multiple sclerosis characterized by alternating rings of spared myelin and demyelination. Diagnosis is based on MRI, but very few data are available concerning the lesion features using serial proton magnetic resonance spectroscopy (1H-MRS). We report 1H-MRS initial findings and disease course in one case of Balo's concentric sclerosis. The first 1H-MRS study of 2 concentric ring-enhanced lesions showed a decreased N-acetyl-aspartate (NAA) peak, an increased choline peak, 2 broad lactate peaks and the presence of a lipid peak at 0.9 ppm. Six months later, 1H-MRS showed a decrease of choline peak, whereas the lactate peak had disappeared. The NAA peak was still at a low level. These findings are similar to those reported in demyelinating disorders, such as multiple sclerosis. Thus, in Balo's concentric sclerosis, 1H-MRS may provide neurochemical arguments for inflammation and demyelination, and indicate the severity of axonal damage and recovery.

Tissue preconditioning may explain concentric lesions in Baló's type of multiple sclerosis

Lesions of Baló's concentric sclerosis are characterized by alternating layers of myelinated and demyelinated tissue. The reason for concentric demyelination in this variant of multiple sclerosis is unclear. In the present study we investigated the immunopathology in autopsy tissue of 14 patients with acute multiple sclerosis or fulminant exacerbations of chronic multiple sclerosis with Baló-type lesions in the CNS, focusing on the patterns of tissue injury in actively demyelinating lesions. We found that all active concentric lesions followed a pattern of demyelination that bears resemblances to hypoxia-like tissue injury. This was associated with high expression of inducible nitric oxide synthase in macrophages and microglia. At the edge of active lesions and, less consistently, in the outermost layer of preserved myelin, proteins involved in tissue preconditioning, such as hypoxia-inducible factor 1alpha and heat-shock protein 70, were expressed mainly in oligodendrocytes and to a lesser degree also in astrocytes and macrophages. Due to their neuroprotective effects, the rim of periplaque tissue, where these proteins are expressed, may be resistant to further damage in an expanding lesion and may therefore remain as a layer of preserved myelinated tissue.

Sclérose concentrique de Balò chez un patient nord-africain

Balo's concentric sclerosis is a rare variant of multiple sclerosis described by Balo in 1928. It is characterized by alternating rings of demyelination and spared myelin. We report a case of Balo's concentric sclerosis diagnosed by the typical MRI findings of concentric rings of demyelination. Medullar and brain localisation were found and clinical course was good under intravenous corticosteroids. MRI provides the best diagnostic information for Balo's concentric sclerosis, allowing early diagnosis and treatment.

Marburg type and Bal�?s concentric sclerosis: rare and acute variants of multiple sclerosis

Marburg type and Balò's concentric sclerosis are considered particular variants of multiple sclerosis, clinically characterized by a severe, rapidly evolving clinical course, and by unusual neuropathological changes, often large tumor-like demyelinating plaques in Marburg type and concentric layers of partial demyelination alternating with demyelinating bands in Balò's concentric sclerosis. These forms now can be diagnosed in vivo, with complete clinical and laboratory examination and MRI follow up. Although in some patients a favourable clinical course has been described, the poor prognosis of the majority of these cases justifies a treatment with intense immunosuppression.

Lessons from the neuropathology of atypical forms of multiple sclerosis

Multiple sclerosis (MS) is characterized by multiple demyelinated inflammatory lesions disseminated in the central nervous system (CNS). Additional features of MS pathology include axonal loss and gliosis. Remyelination may take place predominantly in the early stages of lesion formation. Pathologically, important inter-individual differences have been observed with respect to oligodendrocyte preservation. Furthermore, different mechanisms of demyelination, such as T-cell/macrophage-mediated demyelination, antibody/complement-mediated demyelination, and primary damage of the oligodendrocyte have been observed in individual MS patients. Atypical MS forms, such as Marburg's acute MS, Devic's neuromyelits optica, Balò's concentric sclerosis, and Schilder's diffuse sclerosis share key aspects of MS pathology, however, each of them harbors characteristic discriminative features. Devic's neuromyelitis optica may represent the prototypical disease with antibody/complement-mediated demyelination, whereas cases with Balò's concentric sclerosis show oligodendrocyte dystrophy. Acute disseminated encephalomyelitis (ADEM) may be regarded as a related condition lacking extensive demyelination. Thus, atypical MS forms may help to elucidate pathogenic mechanisms in MS.

Balo's concentric sclerosis

We report a case of Balo's concentric sclerosis with peculiar MRI findings. Unlike previously published cases all concentric rings in our case showed marked enhancement, supporting the view of synchronous active demyelination in the lesion. Follow-up MRI disclosed a change of the lesions into a confluent pattern more resembling a typical large MS plaque. There were no oligoclonal bands or intrathecal Ig-G synthesis. The hypothesis concerning the pathophysiology of the lesions' typical and peculiar morphological appearance and its relationship to multiple sclerosis are briefly discussed.

Baló's concentric sclerosis: surviving normal myelin in a patient with a relapsing–remitting clinical course

Baló's concentric sclerosis: surviving normal myelin in a patient with a relapsing–remitting clinical course