Medscape is available in 5 Language Editions – Choose your Edition here.


Diffuse Sclerosis Workup

  • Author: Robert Stanley Rust, Jr, MD, MA; Chief Editor: Niranjan N Singh, MD, DM  more...
Updated: Apr 14, 2016

Laboratory Studies

See the list below:

  • No specific features of this disease are revealed on routine laboratory studies.
  • As has been noted, results of serum very long chain fatty acid studies and adrenal function studies must be proven normal. If the pattern of abnormality of the findings of these studies is consistent, the alternative diagnosis of adrenoleukodystrophy should be made.
  • EEG and CSF analysis must be undertaken in cases suspected to be examples of Schilder disease. EEG abnormalities such as periodic lateralized epileptiform discharges (PLEDs) suggest the alternative diagnosis of SSPE or progressive rubella panencephalitis. These diagnoses are supported by demonstration of abnormalities on the CSF immune profile, such as oligoclonal bands or elevation of the CSF serum immunoglobulin G (IgG) index or CSF IgG synthetic rate. The diagnosis of either of these entities is confirmed by demonstration of elevated rubeola or rubella titers in CSF.
  • Every effort should be made to identify a possible infectious cause in acute or fulminant cases. This effort should include viral cultures of CSF, nasal or oropharyngeal secretions, and rectal swab. Acute titers for such infectious agents as brucella; Bartonella; Ebstein-Barr virus; cytomegalovirus; Mycoplasma; herpesviruses I, II, or VI; and other infectious agents should be assayed, depending upon the clinical circumstances.

Imaging Studies

See the list below:

  • MRI studies should demonstrate 1 or 2 large confluent lesions in the deep white matter, usually the centrum semiovale, that are bright on T2 weighting. Lesions should be at least 2 cm in size in 2 of 3 dimensions.
    • When 2 lesions are found, 1 lesion should in most cases be located in each hemisphere.
    • Note that one fairly recent case that may be an example of Schilder disease manifested 2 large lesions in 1 hemisphere and none in the other.
    • No additional lesions should be observed on imaging of the brain or spinal cord, a circumstance that may imply the presence of multiple sclerosis, acute disseminated encephalomyelitis, or some other alternative diagnosis.
  • Diagnosis cannot ever be made upon the basis of imaging characteristics alone. MRI findings suggesting the presence of Schilder disease may be most often found in patients with multiple sclerosis. In such cases, in addition to large lesions, smaller multiple sclerosis–like lesions, including black holes, may be found on close inspection, suggesting the diagnosis of what Poser has termed transitional sclerosis rather than diffuse sclerosis. Poser found that most of the cases that have been reported as Schilder disease for which sufficient information is available fall into the transitional sclerosis category, a category that in all likelihood consists almost entirely of cases of multiple sclerosis with the possible inclusion of some cases of acute disseminated encephalomyelitis.

Other Tests

See the list below:

  • Sequential EEG studies show progressive deterioration in background organization, with an appearance that is predominantly that of high-voltage irregular slowing.
    • Intermittent paroxysmal discharges may be observed and may include paroxysmal slowing or spikes. These discharges may be focal, unilateral, bilateral, or generalized.
    • The presence of periodic lateralizing discharges or other pseudorhythmical high-voltage discharges should suggest the alternative diagnosis of SSPE.


See the list below:

  • Brain biopsy specimens may be required to exclude infection, as well as tumors and vasculitic or other inflammatory processes (eg, primary CNS vasculitis, sarcoidosis, histiocytic lymphangiomatosis). Brain biopsy results cannot be relied upon to distinguish multiple sclerosis from acute disseminated encephalomyelitis.
  • Lumbar puncture should be performed in all cases, especially in order to obtain measles antibody titers to rule out the alternative diagnosis of SSPE.
    • In patients with Schilder disease, CSF may be normal or may contain 10-60 monocytic cells (lymphs and monocytes).
    • Elevation of CSF protein is more frequently encountered in Schilder disease than in multiple sclerosis, but it is seldom higher than 100 mg/dL.
    • Elevation of CSF IgG is found in 50-60% of cases; prevalence for this abnormality is higher than in acute disseminated encephalomyelitis, lower than in multiple sclerosis or adrenoleukodystrophy, and much lower than is usually found in SSPE.
    • Very little data exist on the IgG index in Schilder disease. Oligoclonal bands have been found in one case.


No staging for Schilder disease has been proposed.

Contributor Information and Disclosures

Robert Stanley Rust, Jr, MD, MA Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia School of Medicine; Chair-Elect, Child Neurology Section, American Academy of Neurology

Robert Stanley Rust, Jr, MD, MA is a member of the following medical societies: Child Neurology Society, Society for Pediatric Research, American Headache Society, International Child Neurology Association, American Academy of Neurology, American Epilepsy Society, American Neurological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Niranjan N Singh, MD, DM Associate Professor of Neurology, University of Missouri-Columbia School of Medicine

Niranjan N Singh, MD, DM is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Headache Society

Disclosure: Nothing to disclose.

Additional Contributors

William J Nowack, MD Associate Professor, Epilepsy Center, Department of Neurology, University of Kansas Medical Center

William J Nowack, MD is a member of the following medical societies: American Academy of Neurology, Biomedical Engineering Society, American Clinical Neurophysiology Society, American Epilepsy Society, EEG and Clinical Neuroscience Society, American Medical Informatics Association

Disclosure: Nothing to disclose.

  1. Schilder P. Zur Kenntnis der sogenannten diffusen Sklerose. Z Ges Neurol Psychiatr. 1912. 10:1-60.

  2. Karussis D. The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review. J Autoimmun. 2014 Feb-Mar. 48-49:134-42. [Medline].

  3. Schilder P. Zur Frage der Encephalitis periaxialis diffusa. Z Ges Neurol Psychiatr. 1913. 15:359-76.

  4. Schilder P. Die Encephalitis periaxialis diffusa. Arch Psychiatr. 1924. 71:327-356.

  5. Poser CM. Myelinoclastic diffuse sclerosis. Handbook of Clinical Neurology. New York, NY: American Elsevier; 1985. Vol 3: 419-428.

  6. Poser CM. Diffuse-disseminated sclerosis in the adult. J Neuropathol Exp Neurol. 1957. 16:61-78.

  7. Kraus D, Konen O, Straussberg R. Schilder's disease: Non-invasive diagnosis and successful treatment with human immunoglobulins. Eur J Paediatr Neurol. 2011 Sep 16. [Medline].

  8. Barbieri F, Filla A, Grossi D, Orefice G, Perretti A, Cirillo S, et al. Clinical and computerized tomographic study of a case of Schilder's disease. Acta Neurol (Napoli). 1982 Feb. 4(1):57-61. [Medline].

  9. Bielschowsky M, Henneberg R. Uber familiare diffuse Sklerose (Leukodystrophia cerebri progressiva hereditaria). J Psychol Neurol. 1928. 36:131-81.

  10. Cala LA, Mastaglia FL. Computerised tomography findings in multiple sclerosis and Schilder's disease. Clin Exp Neurol. 1977. 14:229-36. [Medline].

  11. Cotrufo R, Salvati G, Morcaldi L, Giordano GG, Guazzi GC. [What is Schilder's disease? Biological study of an unusual neuro-endocrine process]. Riv Patol Nerv Ment. 1968 Apr. 89(2):133-52. [Medline].

  12. Dupel-Pottier C. [Diagnostic criteria of borderline forms of multiple sclerosis]. Rev Neurol (Paris). 2001 Sep. 157(8-9 Pt 2):935-43. [Medline].

  13. Fernández-Jaén A, Martínez-Bermejo A, Gutiérrez-Molina M, López-Martín V, Tendero A, Arcas J, et al. [Schilder's diffuse myelinoclastic sclerosis]. Rev Neurol. 2001 Jul 1-15. 33(1):16-21. [Medline].

  14. Ferrer I, Fábregves I, Alvarez EF, Vila J. Schilder's disease. A study of the cerebral cortex with Golgi's method. Childs Brain. 1981. 8(4):294-8. [Medline].

  15. Fogli A, Schiffmann R, Bertini E. The effect of genotype on the natural history of eIF2B-related leukodystrophies. Neurology. 2004 May 11. 62(9):1509-17. [Medline].

  16. Foix C, Marie J. La sclerose cerebrale centrolobaire a tendance symetrique. Encephale. 1927. 22:81-126.

  17. Fontaine B. [Borderline forms of multiple sclerosis]. Rev Neurol (Paris). 2001 Sep. 157(8-9 Pt 2):929-34. [Medline].

  18. Haberfeld W, Spieler F. Zur diffusen Sklerose des Hirns und Ruckenmarks. Dtsch Z Nervenheilkd. 1910. 40:436-63.

  19. Heubner O. Uber diffuse Hirnsklerose. Charite-Ann. 1897. 22:298-310.

  20. Hogan EL, Joseph KC, Hurt JP, Krigman MR. Schilder's diffuse sclerosis: a biochemical and ultrastructural study of myelinoclastic demyelinaton. Acta Neuropathol. 1972. 20(2):85-95. [Medline].

  21. Iwanowski L, Jedrzejewska A, Dydyk L. [Transitional form of disseminated and diffuse sclerosis during the period of exacerbation]. Neuropatol Pol. 1972. 10(1):79-85. [Medline].

  22. Jankowski K. A case of Schilder's diffuse sclerosis diagnosed clinically schizophrenia. Acta Neuropathol. 1963. 2:302-305.

  23. Kotil K, Kalayci M, Köseoglu T, Tugrul A. Myelinoclastic diffuse sclerosis (Schilder's disease): report of a case and review of the literature. Br J Neurosurg. 2002 Oct. 16(5):516-9. [Medline].

  24. Kurul S, Cakmakçi H, Dirik E, Kovanlikaya A. Schilder's disease: case study with serial neuroimaging. J Child Neurol. 2003 Jan. 18(1):58-61. [Medline].

  25. Lhermitte F, Escourolle R, Hauw JJ, Gray F, Serdaru M, Lyon-Caen O. [Necrotic aspects of multiple sclerosis and Schilder's disease (author's transl)]. Rev Neurol (Paris). 1981. 137(10):589-600. [Medline].

  26. Lumsden CE. Fundamental problems i the pathology of multiple sclerosis and allied demyelinating diseases. Br Med J. 1951. 1:1035-1043.

  27. Marbrug O. Die sogenannte 'akute multiple Sklerose' (Encephalomyelitis periaxialis scleroticans). Jahrb Psychiatr Neurol. 1906. 27:211-312.

  28. Marie P, Foix C. Triplegie spasmodique, sclerose intracerebrale centrolobaire et symetrique. Rev Neurol. 1913. 21:346.

  29. Marks E, Miszczak J. [Case of late form of Schilder's disease]. Neurol Neurochir Pol. 1972 Mar-Apr. 6(2):301-3. [Medline].

  30. Miyagawa K, Ando S, Seino M, Murofushi K. [An autopsy case of inflammatory diffuse sclerosis (adult case of Schilder's disease)--clinicopathological study (author's transl)]. Seishin Shinkeigaku Zasshi. 1976 Dec. 78(12):815-28. [Medline].

  31. Norman MG, Waisberg HA, Lowden JA. Progressive deafness and dementia in an 8-year-old boy. J Pediatr. 1975 May. 86(5):805-9. [Medline].

  32. Pajak B, Stefanko S, Goldsztajn M. [Acute course of Schilder's disease]. Neurol Neurochir Pol. 1971. 5(2):233-6. [Medline].

  33. Picard E. Case records of the Massachusetts General Hospital. Case 43-1965. N Engl J Med. 1965 Sep 30. 273(14):760-7. [Medline].

  34. Poser CM. Disseminated vasculomyelinopathy. A review of the clinical and pathologic reactions of the nervous system in hyperergic diseases. Acta Neurol Scand. 1969. Suppl 37:3-44. [Medline].

  35. Poser CM. Myelinoclastic diffuse and transitional sclerosis. Handbook of Clinical Neurology. New York, NY: American Elsevier; 1970. Vol 9: 469-84.

  36. Poser CM, Brinar VV. The nature of multiple sclerosis. Clin Neurol Neurosurg. 2004 Jun. 106(3):159-71. [Medline].

  37. Poser CM, Goutières F, Carpentier MA, Aicardi J. Schilder's myelinoclastic diffuse sclerosis. Pediatrics. 1986 Jan. 77(1):107-12. [Medline].

  38. Poser CM, Van Bogaert L. Natural history and evolution of the concept of Schilder's diffuse sclerosis. Acta Neurol Scand. 1956. 31:285-331.

  39. Tanaka J, Garcia JH, Khurana R. Unusual demyelinating disease. A form of diffuse-disseminated sclerosis. Neurology. 1975 Jun. 25(6):588-93. [Medline].

  40. Van Bogaert L, De Busscher J. Sur la sclerose inflammatoire de la substance blanche des hemispheres. Rev Neurol. 1939. 71:679-701.

  41. Van Gehuchten P, Brucher JM. La forme transitionelle de la sclerose cerebrale diffuse de Schilder. Rev Neurol. 1961. 104:108-125.

  42. Vanden Herrewegen M, Chamoles N. [Recent study on the significance of diffuse sclerosis of the Schilder type (1912) in children. 1. Anatomoclinical aspect of a sporadic case]. Acta Neurol Psychiatr Belg. 1968 Nov. 68(11):837-50. [Medline].

  43. Walker E. Case records of the MGH - leukoencephalitis, diffuse sclerosis (Schilder's disease). N Engl J Med. 1962. 266:191-96.

  44. Watanabe I, Muller J. Cavitating "diffuse sclerosis". J Neuropathol Exp Neurol. 1967 Jul. 26(3):437-55. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.