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

Abstract

Background Myelinoclastic 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. Objective To compare the cerebrospinal fluid (CSF) features of MDS with those of MS. Methods Retrospective analysis of the CSF profile of all patients with MDS reported in the medical literature between 1960 and 2018. Results The 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. Conclusion In 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.

Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients

“…For example, in myelin oligodendrocyte glycoprotein-IgG-associated encephalomyelitis (MOG-EM) [ 89 ], a normal CSF has been observed in ~ 10% of all samples, both in children and adults, strongly depending on lesion sites (more commonly normal in optic neuritis than in brain disease, and least frequently in spinal cord disease) and OCB are missing in around 90% in this condition [ 13 , 14 ]. Similarly, a lack of intrathecal IgG synthesis has been observed in the vast majority of patients with AQP4-IgG-positive NMOSD [ 15 , 90 , 91 ], in LGI1-IgG-associated encephalitis [ 92 , 93 ], and in IgLON5-IgG-positive encephalomyelitis [ 92 ]), in a subset of patients with other CNS disorders of supposed autoimmune etiology such as Balo’s concentric sclerosis [ 17 ], Schilder’s disease [ 18 ], histopathologically defined “pattern II” and “pattern III” MS [ 16 ].…”

“…Methods were adopted from our previous studies on CSF findings in inflammatory CNS disorders [ 13 – 18 ] adhering to the German Guidelines on CSF diagnostics of the German Society for CSF Diagnostics and Clinical Neurochemistry and the German Society of Neurology [ 19 – 21 ].…”

Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 1: Results from 163 lumbar punctures in 100 adult patients

“…With the re-integration of OCB in the latest revision of the diagnostic criteria for MS [79] and the demonstration of substantial differences in CSF profiles between MS and its most important mimics [36,38,46,57,[80][81][82], LP may be performed more often in the future. Although LP is a relatively safe procedure and routinely used in many countries, adverse event such as headache (post-puncture CSF pressure syndrome, the frequency of which can be substantially lowered by use of so-called atraumatic 22-24 gauge needles with conical tip and lateral opening ["Sprotte needles"]), radicular symptoms, non-specific back pain, disc prolapse, or aseptic disc necrosis (extremely rare), bleeding or infection rarely occur and a number of absolute (increased intracranial pressure with progressive herniation as indicated clinically and/or by MRI or CT; inflammatory infiltration of the skin in the puncture area) and relative (platelet counts < 50 GPt/L; therapeutic heparinization; oral anticoagulation) contraindications exist [33].…”

Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 2: Results from 108 lumbar punctures in 80 pediatric patients

“…With the re-integration of OCB in the latest revision of the diagnostic criteria for MS [87] and the demonstration of substantial differences in CSF profiles between MS and its most important mimics [44,46,55,64,[88][89][90], LP may be performed more often in the future. Although LP is a relatively safe procedure and routinely used in many countries, adverse event such as headache (post-puncture CSF pressure syndrome, the frequency of which can be substantially lowered by use of so-called atraumatic 22-24 gauge needles with conical tip and lateral opening ["Sprotte needles"]), radicular symptoms, non-specific back pain, disc prolapse or aseptic disc necrosis (extremely rare), bleeding, or infection rarely occur and a number of absolute (increased intracranial pressure with progressive herniation as indicated clinically and/or by MRI or CT; inflammatory infiltration of the skin in the puncture area) and relative (platelet counts < 50 GPt/L; therapeutic heparinization; oral anticoagulation) contraindications exist [40].…”