Other Autoimmune CNS Demyelinating Disorders

47 Other Autoimmune CNS Demyelinating Disorders



Mary Anne Muriello, Claudia J. Chaves, H. Royden Jones, Jr.


There are three very rare acute demyelinating central nervous system disorders that are distinct from multiple sclerosis (MS). These initially appear de novo in previously healthy individuals. Although some instances may occur in isolation, and respond to very high dose immunosuppressive therapy, on other occasions their consequences can be devastating.



Neuromyelitis Optica / Devic Disease


Optic neuritis (ON) is very commonly the first clinical event experienced by patients who later develop full-blown multiple sclerosis. Approximately 50% of ON patients will demonstrate clinical evidence of MS within 5–6 years of onset. Rarely an occasional patient, presenting with what seems to be classic ON, very soon thereafter develops an acute and clinically severe myelopathy. The combination represents an entirely different nosologic and pathophysiologic entity from MS. This entity, known as neuromyelitis optica (NMO), is a syndrome that is both relapsing and much more rapidly disabling than occurs in the typical MS patient. For example, about half of NMO patients become wheel chair bound within 5 years and almost two thirds will be legally blind (no better than 20/200) within that same time frame. There is no chronic progressive stage as most often eventually occurs in classic multiple sclerosis. NMO also has a relatively high early mortality, something almost unheard of in MS. These relatively rare NMO deaths usually follow disease extension into the brainstem and/or upper cervical cord.



Diagnosis


The diagnosis of NMO, rather than MS, in a patient with a history of ON (Fig. 47-1) and myelitis is largely dependent on documentation of longitudinally extensive spinal cord lesions (more than three spinal segments). Such extensive intramedullary spinal cord lesions are unique to NMO in contrast to the very short segment MRI findings in MS (Fig. 47-2).


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Figure 47-1 Optic Nerve Atrophy.


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Figure 47-2 Neuromyelitis Optica.


A very specific NMO-IgG serum autoantibody is identified that binds to the central nervous system (CNS)–dominant water channel aquaporin-4, a structure that is normally present on astrocytes. This leads to the primary pathologic change, namely, loss of this aquaporin-4 water channel protein. This is occasionally associated with secondary demyelination. Hypothalamic and periventricular demyelination, the latter previously thought to be almost MS specific, are now also recognized to be associated with NMO-IgG/anti-AQP4 seropositivity. This particular distribution of lesions corresponds with the site of AQP4 expression within the brain. Preliminary experiments suggest that anti-AQP4 autoantibodies are pathogenic. This antibody has a high sensitivity and specificity for NMO being present in at least 75% of these cases; its presence now provides a specific diagnostic modality. This totally contrasts with MS, where there is nothing absolutely specific present to confirm that diagnosis.



Prognosis


When one is confronted with a new case of ON, the testing for NMO-related anti-AQP4 antibodies is very important diagnostically as well as prognostically. In this setting, the finding of this specific seropositivity predicts poor future visual outcome, and possibly rapid onset of NMO. In the converse, the patient presenting with longitudinally extensive transverse myelitis (LETM) and who is found to be antibody positive for the NMO antibody has more than a 50% chance of developing ON or recurrent severe ON within just 1 year. This is an important designation as NMO has a much worse prognosis than MS per se because the antibody-positive NMO patient does not respond to the usual immunomodulatory treatments that are often initially effective for MS.



Treatment

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Jun 4, 2016 | Posted by in NEUROLOGY | Comments Off on Other Autoimmune CNS Demyelinating Disorders

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