Inflammatory demyelinating diseases of the central nervous system

Lore & Background

Inflammatory demyelinating diseases (IDDs) are a heterogeneous group of conditions that damage myelin, the protective sheath of nerve fibers, occurring against an acute or chronic inflammatory background. They are often grouped with multiple sclerosis, though some consider them distinct diseases while others see them as a spectrum differing in chronicity, severity, and clinical course. Multiple sclerosis itself is considered by some to be a syndrome rather than a single disease. As of 2019, three auto-antibodies had been found in atypical MS, giving rise to separate diseases: anti-AQP4 diseases, anti-MOG, and anti-neurofascin spectrums. A LHON-associated MS has also been reported, and there have been inconclusive reports of TNF-α blockers inducing demyelinating disorders.

Reader's Guide

The classification of inflammatory demyelinating diseases has evolved significantly with the discovery of specific auto-antibodies. Anti-AQP4 diseases were originally found in neuromyelitis optica and now encompass a spectrum including seropositive Devic's disease, limited forms such as longitudinally extensive myelitis, Asian optic-spinal MS, and some cases of tumefactive multiple sclerosis. Anti-MOG associated encephalomyelitis can present as anti-MOG autoimmune encephalomyelitis, negative NMO, or atypical multiple sclerosis, and includes conditions such as recurrent acute disseminated encephalomyelitis, isolated optic neuritis, and CRION (chronic relapsing inflammatory optic neuritis). Anti-neurofascin demyelinating diseases, previously considered a subtype of MS, now account for around 10% of MS cases and involve autoantibodies against nodal and paranodal proteins including NF186, NF155, contactin 1, CASPR1, and gliomedin. Demyelination associated with anti-TNF therapy has been reported, with lesions fulfilling pathological diagnostic criteria for MS and classified as pattern II in the Lassman/Lucchinetti system. LHON-associated MS is a presentation of LHON with MS-like CNS damage, not due to auto-antibodies but to defective mitochondria. Several variants remain idiopathic and are considered inside the MS-spectrum, including pseudotumefactive variants such as Marburg multiple sclerosis, Balo concentric sclerosis, Schilder disease, and solitary sclerosis.

Did You Know?

• Anti-neurofascin diseases are rare and distinct from MS, with a far lower prevalence than the 10% figure sometimes suggested.
• Double positivity for AQP4 and MOG autoantibodies is extremely rare and not a recognized typical presentation in NMO patients.
• Anti-TNF therapy can produce CNS-demyelination, but Dawson fingers are not exclusive to MS and can occur in other demyelinating conditions.