Childhood autoimmune neurologic diseases of the central nervous system

An autoimmune mechanism for ADEM and MS can be supported by the similar patterns of pathologic changes seen in both diseases with the animal model EAE induced by inoculating animals with nervous tissue and the occurrence of ADEM in patients exposed to nervous tissue during vaccination. Whereas there are no universally agreed-upon criteria for the diagnosis of ADEM, a combination of prodromal illness or preceding vaccination, MRI signs of demyelination, and an acute presentation of neurologic symptoms are the triad most commonly looked for in making the diagnosis of ADEM. An ever-increasing number of infections and vaccinations (nonspecific URIs being most common) has been associated with ADEM. Fever and encephalopathy are seen frequently at presentation. Seizures also are common, as are cranial nerve abnormalities and motor symptoms. A mild pleocytosis or protein elevation is found in the majority of patients with ADEM. Intrathecal IgG synthesis and oligoclonal bands are relatively infrequent but should not be considered inconsistent with the diagnosis of ADEM. White matter changes on T2 in a bilateral although asymmetric distribution with relative sparing of the periventricular region with or without deep gray matter involvement is consistent and to some a requirement for the diagnosis. Low-dose steroids have no beneficial effect in the treatment of ADEM and may be contraindicated. High-dose steroids may have a beneficial effect, particularly in more prolonged illnesses, although the evidence is primarily anecdotal. If steroids are used to improve morbidity, 30 mg/kg/d of methylprednisolone for three to five days is the dose with a six-week taper to reduce the risk of recurrence. The prodromal infection may be a major factor in the ultimate mortality and morbidity of the disease. The current mortality of ADEM is quite low. Whether or not this is an effect of different triggering agents or changes in medical care cannot be determined. In larger series of patients with ADEM, 10% to 20% of children experience some sort of recurrence with the majority occurring in the initial one to two months after the first event. This is sometimes associated with steroid withdrawal. A second group of children have a late second recurrence that clinically may not be MS but a recurrence of ADEM, although longer follow-up may change that assessment. Two months should be allowed before a second relapse is considered a manifestation of MS, whereas a second attack also may occur years after an initial attack of ADEM and still be consistent with ADEM recurrence. MS does occur during childhood, with the youngest children at the least risk, and risk increasing with age. The criteria of Poser et al can be used to diagnose MS in childhood [40]. The presentation of MS in childhood is most often sensory, motor, and brainstem signs and symptoms. A relapsing-remitting course is most common with a first relapse occurring in the year after presentation. MRI findings in MS typically show periventricular changes. Oligoclonal bands and CSF IgG synthesis are found in the majority. Treatments of childhood MS have not been studied adequately, but, when treatments studied in adults are used in children, they are well tolerated. Efficacy has not been shown. The long-term outcome of MS in childhood can be either severe or benign with no clear consensus that childhood MS is either a less or more severe disease than the adult form. ATM and ON treatments and outcomes are particularly difficult to evaluate because of the heterogeneity of populations included in case series and the small numbers reported. Steroids are used with anecdotal reports of their superiority to nontreatment. Outcome in ATM often can be poor, whereas in ON it rarely is. A multinational collaborative effort to study and collect the large numbers necessary to address the important questions in these childhood autoimmune disorders would be of great benefit and the only way likely to demonstrate good evidenced-based medicine practiced in this field.