Baló's concentric sclerosis is immunologically distinct from multiple sclerosis: results from retrospective analysis of almost 150 lumbar punctures

Abstract

Background: Baló's concentric sclerosis (BCS) is a rare inflammatory demyelinating disorder of the central nervous system characterised by concentric layers of demyelination. It is unclear whether BCS is a variant of multiple sclerosis (MS) or a disease entity in its own right.

Objective: To compare the cerebrospinal fluid (CSF) features of BCS to those of MS.

Methods: Retrospective analysis of the CSF profile of all patients with BCS reported in the medical literature between 1980 and 2017.

Results: In total, the results of 146 lumbar punctures (LP) in 132 patients were analysed. The most striking finding was a lack of CSF-restricted oligoclonal bands (OCB) in 66% (56/85) of all LP in the total BCS group, in 74% (14/19) in the subgroup of patients with both MRI and histological evidence for BCS, and in 82% (18/22) in the subgroup of patients with highest radiological confidence (high MRI quality, ≥ 3 layers of demyelination). OCB disappeared in 1/2 initially OCB-positive patients. These findings are in stark contrast to MS, in which OCB are present in ≥ 95% of patients and are thought to remain stably detectable over the entire course of disease (p < 0.000001). OCB frequency was low both in 'historic' patients (1980-2009; 37%) and in more recent patients (2010-2017; 31%). OCB-positive and OCB-negative patients did not differ significantly with regard to age, sex, disease duration, number of Baló-like lesions on MRI, number of relapses, treatment or final outcome. In accordance with the high rate of OCB negativity, Link's IgG index was negative in 63% of all tested samples (p < 0.000001 vs. MS). CSF pleocytosis was present in 28% (27/96; p < 0.000001 vs. MS) and elevated CSF total protein levels in 41% (31/76) of samples.

Conclusion: OCB and IgG index frequencies in BCS are much more similar to those reported in neuromyelitis optica or myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis than to those in MS. Our findings suggest that in most cases BCS-like lesions denote the presence of a disease entity immunologically distinct from MS. In addition, we provide data on the demographics, clinical course and radiological features of BCS based on the largest cohort analysed to date.

Keywords: Baló; Baló’s concentric sclerosis (BCS); Cerebrospinal fluid (CSF); Diagnosis; Histopathology; Immunology/immunopathology; Intrathecal IgG synthesis; Link’s IgG index; Lumbar puncture; Magnetic resonance imaging; Multiple sclerosis (MS); Oligoclonal bands (OCB); Pattern III MS; Pleocytosis; Review of the literature.

Fig. 1

Frequency of CSF-restricted OCB in MS (N = 276) [17], BCS (present study; N = 146), NMOSD (N = 144) [4] and MOG-EM (N = 45) [11]. AQP4+ aquaporin-4-IgG-positive, AQP4− aquaporin-4-IgG-negative, BCS Baló’s concentric sclerosis, HQ-MRI high-quality MRI subgroup (see the ‘Results’ section for details), MOG-EM myelin oligodendrocyte glycoprotein antibody-positive encephalomyelitis, MS multiple sclerosis, NMOSD neuromyelitis optica spectrum disorders