Diffuse Sclerosis Treatment & Management
- Author: Robert Stanley Rust, Jr, MD, MA; Chief Editor: Niranjan N Singh, MD, DM more...
The underlying cause of Schilder disease remains unknown, particularly if limited to those cases that conform to the 1912 type. Implicit in that definition is inexorable disease progression. As has been noted, the definition then applies to approximately 9 of all reported cases. Whether the 1912 type cases are to be considered responsive to corticosteroid treatment and whether such treatment would have rendered moot the progressive nature of the illness that Schilder first defined is unknown.
If any wider definition is applied, particularly one based upon radiographic criteria, then a number of inflammatory illnesses are likely to be included, some of which are treatable. Even with radiographic diagnosis, adrenoleukodystrophy, SSPE, progressive rubella panencephalitis, and those forms of collagen vascular disease and encephalitis that can be excluded by CSF or other laboratory studies are presumably excluded from consideration as examples of diffuse sclerosis (Schilder 1912 type).
Based upon such radiologic diagnosis, the critical approach to treatment is to ascertain whether the lesion is responsive to the administration of high-dose intravenous corticosteroids.
General practice in such cases currently entails methylprednisolone administration of doses of 20-30 mg/kg each morning for each of 3-5 successive mornings, followed by a taper of oral corticosteroids. This treatment may be contraindicated by the possible presence of bacterial infections or the unexcluded possibility of herpetic encephalitis. Administration of corticosteroids should be accompanied by the administration of antacids or histamine (H2) receptor antagonists to reduce the risk for formation of Cushing ulcers. Patients should be monitored for such potential adverse effects as hypersensitivity, gastrointestinal bleeding, hypertension, hyperglycemia, hypokalemia, or opportunistic infection. These problems are seldom encountered.
Response to this form of therapy employing this or similar regimens has been documented in a number of single case reports provided over the past decade. Whether the effectiveness of such therapy is pertinent to consideration of strictly interpreted Schilder disease criteria is unclear. In many of these instances where no pathological information was obtained but response to therapy was beneficial, the underlying problem was likely acute disseminated encephalomyelitis or multiple sclerosis. Response to such therapy could also be noted in certain brain tumors (as has been the authors' experience) emulating Schilder disease and perhaps in other entities.
The addition of brain biopsy excludes such diagnoses as brain tumor, vasculitis, collagen vascular process, or encephalitis by the identification of specific pathological changes. In some instances, aspiration or surgical biopsy of large lesions suggesting Schilder disease has been accomplished, and several of these cases have also been reported during the past decade. In such cases, the pathological changes discerned often resemble either multiple sclerosis or acute disseminated encephalomyelitis; the pathological changes of these entities may be quite difficult if not impossible to distinguish on the basis of brain tissue biopsy.
Where such changes are found, the therapy described above, high doses of intravenous corticosteroids, is likely to prove beneficial, although lesions may recur. Some authorities (chiefly those accustomed to treating multiple sclerosis in adolescents and adults) are confident that recurrence of such lesions is diagnostic of multiple sclerosis. Other authorities, particularly those whose experience is largely limited to management of acute disseminated encephalomyelitis in prepubescent children, are confident that some of these cases may represent recurrent acute disseminated encephalomyelitis, an entity that the former group of authorities usually maintains does not exist.
This controversy is as yet unresolved, as are those controversies attendant upon the establishment of diagnostic boundaries for Schilder disease. However, several practical points can be made concerning treatment of those patients with radiographic findings suggesting Schilder disease (ie, large lesions of the type discussed above) and who have had all other pertinent differential considerations excluded (eg, vasculitic, tumor-related, collagen vascular, metabolic, other forms of illness).
Cases remaining that suggest the possible diagnosis of Schilder disease (diffuse sclerosis, Schilder disease of the 1912 type) or especially of transitional sclerosis (defined by the presence of small multiple sclerosis–like lesions in deep white matter in addition to large lesions) arising in postpubertal individuals should be considered to be multiple sclerosis until proven otherwise. The additional smaller lesions tend not to be found at the gray-white margin or in deep gray nuclei or thalamus. This diagnosis of multiple sclerosis can be supported in many cases by the fact that the CSF IgG index and oligoclonal band studies are frequently positive.
Many of these cases appear to respond favorably to intravenous steroid therapy, although their subsequent course is likely to be one of continued development of bouts of multiple sclerosis or the assumption of a progressive form of multiple sclerosis. In such cases, consideration must be given to treatment with immunomodulatory agents. That form of treatment is beyond the scope of Schilder disease proper and is not further considered here. Details are available in Multiple Sclerosis.
Cases arising in prepubertal individuals with imaging findings suggestive of Schilder disease, for whom the alternative diagnoses noted above have been excluded (by specific tests), are likely to have an illness that falls within the family of acute disseminated encephalomyelitis. In some of these cases, smaller lesions are found in addition to the 1 or 2 large lesions that raise the possibility of a diagnosis of Schilder disease. In distinction to the group of adults just discussed, these additional lesions tend to be centripetal within the brain, some of them overlying the gray-white margin, and some may be found in deep gray nuclei or the thalamus.
The findings on CSF immune profile studies such as IgG index and oligoclonal bands are usually negative in these patients, although the myelin basic protein assay is frequently elevated. These patients tend to respond very well to a course of high-dose corticosteroids after the fashion discussed above. They may show resolution of illness, in some cases marked by the complete disappearance of large lesions, even those that appear to show central necrosis. Their subsequent course may include one or more recurrences, and in rare instances, the recurrence may be in the spinal cord (particularly the cervical spinal cord) rather than in the brain.
The best way to set either of the previously mentioned 2 groups apart from the largest number of alternative inflammatory, metabolic, or infectious diagnoses is brain biopsy. In some cases from either of the aforementioned groups, the opportunity for aspiration or biopsy is provided by attempts to reduce the volume of such lesions where they are thought to produce significant elevation of intracranial pressure. In a few such cases, intervention has been determined to be beneficial to the patient. In such cases, alternative diagnoses having been excluded, the pathology may be consistent with either multiple sclerosis or acute disseminated encephalomyelitis, entities that are in fact difficult to distinguish on the basis of a biopsy specimen from a single lesion.
In addition to cases that represent either multiple sclerosis or acute disseminated encephalomyelitis but are not found to have any of the alternative diagnoses noted above, the possibility remains that a very rare and small group of patients have a discrete disease that should be termed diffuse sclerosis (Schilder disease 1912 type). The efficacy of various treatment interventions and prognosis remains unclear.
In addition to treatment with corticosteroids, medical management entails support for breathing, circulation, nutrition, and attention to maintaining normal metabolic profiles during the acute phase of illness. Management includes in fulminant cases prevention of the development of skin breakdown or ulceration or of nosocomial infection from intravenous lines or other sources.
Neurosurgical care may be required for obtaining a lesion biopsy. In some reported instances, neurosurgical aspiration of large lesions suggesting Schilder disease, particularly those with what appears to be central necrosis, has been judged valuable for both diagnostic purposes and alleviation of pressure.
Consultations may be required from infectious disease specialists, rheumatologists, child neurologists, specialists in the diagnosis and management of multiple sclerosis, neurosurgeons, intensivists, and various therapists.
No specific diet is indicated for patients with Schilder disease. Those who appear to have Schilder disease but are found instead to have adrenoleukodystrophy have been treated with dietary modifications, the efficacy of which remains uncertain. Consideration of this topic is beyond the scope of this review.
No specific limitations to activity exist. Patients who are thought likely to have transitional sclerosis, and therefore are likely to have multiple sclerosis, may experience exacerbations of symptoms of illness because of exposure to heat, poor nutrition, or because they become overtired.
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