In addition, enlisting the support of physical and occupational therapists, visiting nurses, and social workers can be equally important. From the beginning, when patients first inquire about the nature of their illness, they require advice about their daily routine, marriage, pregnancy, the use of drugs, inoculations, and so on. As indicated earlier, the term MS should not be introduced until the diagnosis is certain, and then it should be qualified by a balanced explanation of the symptoms, stressing always the optimistic aspects of the disease. Most patients desire an honest appraisal of their condition and prognosis; some consider the uncertainty of their prognosis worse than their actual disability.
Neuromyelitis Optica (Devic Disease) (See Also Chap. 42)
This disease is characterized by a simultaneous or successive and usually severe involvement of optic nerves and spinal cord. The combination was remarked upon by Clifford Albutt in 1870, and Gault (1894), stimulated by his teacher Devic, devoted his thesis to the subject. Devic subsequently endeavored to crystallize medical thought about a condition that has come to be known as neuromyelitis optica. Its principal features are the acute to subacute onset of blindness in one or both eyes, preceded or followed within days or weeks by a severe transverse or ascending myelitis (Mandler et al, 1998).
While NMO was previously considered a variant of multiple sclerosis (MS), it is now recognized to have distinct clinical, pathological, and immunological features. The singular insight in Devic disease has been the discovery by the group at the Mayo Clinic of a specific circulating autoantibody to the aquaporin-4 water channel protein. Lennon and colleagues reported that the antibody is a marker for NMO in the majority of cases, and that it is virtually absent in MS. In the material of Wingerchuk and colleagues, the presence of the antibody was 76 percent sensitive and 94 percent specific. By using the additional criteria of the presence of 2 of the following, the sensitivity and specificity were 99 and 90 percent: longitudinally extensive myelopathy, positive antibodies and an initial MRI that is not characteristic for MS.
The site of destruction with this antibody is the astrocyte rather than the oligodendrocyte or its myelin extension as occurs in conventional MS. A proportion of patients with what otherwise resembles NMO do not have the characteristic antibody and have more recently been explained by antibodies to myelin oligodendrocyte glycoprotein (MOG), a molecule expressed on the outer lamella of the myelin sheath. After decades of debate, these finds have largely settled the controversy about Devic disease as an independent entity from MS.
The place of disorders with anti-MOG antibodies as a unique clinical entity is being elucidated. The antibodies appear to be referable mainly to children and to be associated with a predominantly monophasic course or several serial monophasic episodes, linking them clinically with ADEM, discussed further on. One interesting feature of these antibodies is that they identify the native form of the MOG glycoprotein and probably eluded understanding for many years because the denatured form was used in antibody assays.
These immunologic findings have led to the conclusion that the Devic process is humoral, in contrast to the primarily cellular-immune mechanism that is proposed for MS (Lucchinetti et al, 2002). Pittock and coworkers have explored the distribution of the antibody and found it to be located in astrocytic end feet adjacent to capillaries, pia, and Virchow-Robin spaces in the periventricular regions surrounding the central canal of the spinal cord. Binding of NMO-IgG to AQP4 causes astrocytic injury through antibody-dependent cell-mediated cytotoxicity and activation of the complement pathway. These signaling pathways attract inflammatory cells including T and B lymphocytes, macrophages, neutrophils, and eosinophils.