eMedicine Specialties > Neurology > Inflammatory and Demyelinating Diseases

Diffuse Sclerosis: Differential Diagnoses & Workup

Author: 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; Chair-Elect, Child Neurology Section, American Academy of Neurology
Contributor Information and Disclosures

Updated: May 22, 2009

Differential Diagnoses

Acute Disseminated Encephalomyelitis
Primary CNS Lymphoma
Aseptic Meningitis
Viral Encephalitis
Brucellosis
Viral Meningitis
Churg-Strauss Disease
Wegener Granulomatosis
Glioblastoma Multiforme
Multiple Sclerosis

Other Problems to Be Considered

Adrenoleukodystrophy
SSPE
Progressive rubella panencephalitis
Mitochondrial cytopathy
Primary CNS vasculitis
Histiocytic lymphangiomatosis
Sarcoidosis
Balo's concentric sclerosis
Alpers syndrome/POLG1 gene defect

Workup

Laboratory Studies

  • 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

  • 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

  • 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.

Procedures

  • 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.

Staging

No staging for Schilder disease has been proposed.

More on Diffuse Sclerosis

Overview: Diffuse Sclerosis
Differential Diagnoses & Workup: Diffuse Sclerosis
Treatment & Medication: Diffuse Sclerosis
Follow-up: Diffuse Sclerosis
References
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Further Reading

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Keywords

diffuse sclerosis, myelinoclastic diffuse sclerosis, Schilder's myelinoclastic diffuse sclerosis, inflammatory myelinoclastic diffuse sclerosis, Schilder's cerebral sclerosis, Schilder's disease, Schilder disease, Schilder-type multiple sclerosis, diffuse sclerosis of the Schilder type, Schilder's disease of the 1912 type, encephalitis periaxialis diffusa

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Contributor Information and Disclosures

Author

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; Chair-Elect, Child Neurology Section, American Academy of Neurology
Robert Stanley Rust Jr, MD, MA is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Headache Society, American Neurological Association, Child Neurology Society, International Child Neurology Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

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, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Electroencephalographic Association, American Medical Informatics Association, and Biomedical Engineering Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale
Richard J Caselli, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, American Neurological Association, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Michael K Racke, MD, Professor of Neurology and Molecular Virology, Immunology, and Medical Genetics, Chairman of Neurology, Chief of Neurology Service, Ohio State University Medical Center
Michael K Racke, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association for the Advancement of Science, American Association of Immunologists, and American Neurological Association
Disclosure: Teva Neuroscience Consulting fee Consulting; Peptimmune Inc. Consulting fee Consulting; Bristol Myers Squibb Consulting fee Consulting; EMD Serono Honoraria Speaking and teaching

 
 
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