Background The diagnosis of multiple sclerosis (MS) is currently based solely
on clinical and magnetic resonance imaging features. However,
histopathological studies have revealed four different patterns of lesion
pathology in patients diagnosed with MS, suggesting that MS may be a
pathologically heterogeneous syndrome rather than a single disease entity.
Objective The aim of this study was to investigate whether patients with
pattern I MS differ from patients with pattern II or III MS with regard to
cerebrospinal fluid (CSF) findings, especially with reference to intrathecal
IgG synthesis, which is found in most patients with MS but is frequently
missing in MS mimics such as aquaporin-4-IgG-positive neuromyelitis optica
spectrum disorders and myelin oligodendrocyte glycoprotein-IgG-positive
encephalomyelitis. Methods Findings from 68 lumbar punctures in patients who
underwent brain biopsy as part of their diagnostic work-up and who could be
unequivocally classified as having pattern I, pattern II or pattern III MS
were analysed retrospectively. Results Oligoclonal bands (OCBs) were present
in 88.2% of samples from pattern I MS patients but in only 27% of samples from
patients with pattern II or pattern III MS (P < 0.00004); moreover, OCBs were
present only transiently in some of the latter patients. A polyspecific
intrathecal IgG response to measles, rubella and/or varicella zoster virus
(so-called MRZ reaction) was previously reported in 60–80% of MS patients, but
was absent in all pattern II or III MS patients tested (P < 0.00001 vs.
previous cohorts). In contrast, the albumin CSF/serum ratio (QAlb), a marker
of blood–CSF barrier function, was more frequently elevated in samples from
pattern II and III MS patients (P < 0.002). Accordingly, QAlb values and
albumin and total protein levels were higher in pattern II and III MS samples
than in pattern I MS samples (P < 0.005, P < 0.009 and P < 0.006,
respectively). Conclusions Patients with pattern II or pattern III MS differ
significantly from patients with pattern I MS as well as from previous,
histologically non-classified MS cohorts with regard to both intrathecal IgG
synthesis and blood–CSF barrier function. Our findings strongly corroborate
the notion that pattern II and pattern III MS are entities distinct from
pattern I MS
