A related but confusing entity, which had been the subject of much discussion in the earlier part of the last century, is that of diffuse sclerosis, or Schilder disease. In these exceptional cases, which are more frequent in childhood and adolescence than adulthood, the cerebrum is the site of diffuse and massive demyelination. Despite the undoubted occurrence of such cases, to call them “Schilder disease” is to refer to a clinical entity of ambiguous standing. The term diffuse sclerosis was first used by Strümpell (1879) to describe the hard texture of the freshly removed brain of an alcoholic; later the term was applied to widespread cerebral gliosis of whatever cause. In 1912, Schilder described an instance of what he considered to be “diffuse sclerosis.” The case was that of a 14-year-old girl with progressive mental deterioration and signs of increased intracranial pressure, terminating fatally after 19 weeks. Postmortem examination disclosed large, well-demarcated areas of demyelination in the white matter of both cerebral hemispheres, as well as a number of smaller demyelinating foci, resembling the common lesions of MS. Because of the similarities of the pathologic changes to those of MS (prominence of the inflammatory reaction and relative sparing of axons), Schilder called this disease encephalitis periaxialis diffusa, bringing it in line with encephalitis periaxialis scleroticans, a term that Marburg had used to describe a case of acute MS. Unfortunately, in subsequent publications, Schilder applied the same term to 2 other conditions of different types. One appears to have been a familial leukodystrophy (probably adrenoleukodystrophy) in a boy, and the other, quite unlike either of the first 2 cases, was suggestive of an infiltrative lymphoma. The last 2 reports seriously confused the subject, and for many years the terms Schilder disease and diffuse sclerosis were indiscriminately attached to quite different conditions.
If one sets aside the hereditary metabolic leukodystrophies and other childhood disorders of cerebral white matter, there remains a characteristic group of cases allied with multiple sclerosis that does, indeed, correspond to Schilder’s original case description of a large tumefactive demyelinating lesions. They are most frequently encountered in children or young adults. As with the case reported by
Ellison and Barron, the disease may follow the course of MS, either steady and unremitting or punctuated by a series of episodes of rapid worsening. The CSF may show changes similar to those in chronic relapsing MS. Death occurs in most patients within a few months or years, but some survive for a decade or longer. In the differential diagnosis, a diffuse cerebral neoplasm (gliomatosis or lymphoma), adrenoleukodystrophy, and progressive multifocal leukoencephalopathy (Chap. 32) are the main considerations. Histologically, the large single focus, as well as the smaller disseminated ones, shows the characteristic features of MS. These features were elaborated by Poser and colleagues in a subsequent (1986) review of this subject.