Schilder’s disease

Schilder’s disease is a very rare, progressive, degenerative, demyelinating disorder of the central nervous system (CNS) that usually begins in childhood and young adulthood ¹. Schilder’s disease is not the same as Addison-Schilder disease (adrenoleukodystrophy), a rare inherited disease characterized by a biochemical abnormality in the myelin. Schilder’s disease is thought to be a variant of multiple sclerosis ². Schilder’s disease is also known as diffuse cerebral sclerosis, diffuse cerebral sclerosis of Schilder, encephalitis periaxialis diffusa or myelinoclastic diffuse sclerosis ³. Schilder’s disease is characterized by one or two extensive, often bilateral and roughly symmetrical demyelinating white matter lesions in the centrum semiovale ³. Schilder’s disease symptoms may include dementia, aphasia, seizures, personality changes, poor attention, tremors, balance instability, incontinence, muscle weakness, headache, vomiting, and vision and speech impairment.

Schilder’s disease was first described in 1912 by the Austrian psychiatrist Paul Ferdinand Schilder (1886–1940) ⁴. Schilder’s disease is incredibly rare, and a recent review of the literature from 1960 to 2018 identified only 66 reported cases.

Treatment for Schilder’s disease follows the established standards in multiple sclerosis and includes corticosteroids, beta-interferon or immunosuppressive therapy, and symptomatic treatment.

How is Schilder’s disease similar to multiple sclerosis?

Schilder’s disease resembles MS (multiple sclerosis) in both its pathology (widespread demyelination of the brain) and some of its symptoms (difficulties with movement, speech and memory, among others).

Schilder’s disease is thought to be a very rare variant of multiple sclerosis that typically begins in childhood and has a more rapidly degenerative course.

Is Schilder’s disease inherited?

No, Schilder’s disease is not inherited. Schilder’s disease is sometimes confused with Addison-Schilder disease, an inherited, biochemical abnormality in the myelin.

Is Schilder’s disease contagious?

No, Schilder’s disease is not contagious.

Schilder’s disease causes

The underlying cause of Schilder’s disease is unknown. Schilder’s disease often occurs shortly after an infectious illness and may begin with headache, a general feeling of discomfort or illness, and fever. Symptoms are caused by widespread patches of demyelination throughout the brain and spinal cord, resulting in slowed transmission of nerve signals.

Schilder’s disease symptoms

The symptoms of Schilder’s disease could include the following:

• Weakness on one side of the body (hemiparesis)
• Slowness of movement (psychomotor retardation)
• Seizures
• Difficulty with speech (dysarthria)
• Visual and hearing impairment
• Irritability
• Memory problems
• Personality changes
• Gradual loss of awareness and responsiveness
• Gradual inability over time to maintain nutritional status, causing patients to become increasingly thin and malnourished
• Gradual loss of bowel and bladder function as the disease progresses
• Impact on vital functions of respiration, blood pressure and heart rate in advanced disease

Schilder’s disease diagnosis

Because there are no specific criteria for diagnosis, there is debate about the most appropriate way to definitively diagnose the disease.

Schilder’s disease is diagnosed based on the findings on magnetic resonance imaging (MRI). Clinicians attempt to rule out other diseases that can cause symptoms similar to Schilder’s disease such as intracranial neoplasm, abscess and genetic conditions, by performing blood work and spinal fluid analysis.

The diagnostic criteria established by Poser in 1985 require 6 elements ⁵:

1. One or two roughly symmetrical large plaques (lesions or scars) are manifest, and if more than 1 is present, 1 should be in each brain hemisphere, chiefly in the centrum semiovale. Plaques are greater than 2 cm in 2 of 3 dimensions.
2. No other lesions are demonstrable by clinical, paraclinical, or imaging data.
3. No abnormalities of the peripheral nervous system are demonstrable.
4. Results of adrenal function studies are normal.
5. Serum very long chain fatty acids are normal.
6. Pathological analysis by autopsy or biopsy demonstrates histologic changes consistent with subacute or chronic myelinoclastic diffuse sclerosis, changes which in essence cannot be distinguished from those of multiple sclerosis.

Schilder’s disease treatment

The goals of treatment for Schilder’s disease are to relieve symptoms and maintain function as long as possible. Physiotherapy, occupational therapy and nutritional support in the later stages are commonly employed. Corticosteroids have been shown to be effective in some patients. Additional treatment could include intravenous immunoglobulin (IVIg), rituximab and/or immunosuppressive drugs.

Schilder’s disease prognosis

As with multiple sclerosis, the course and prognosis of Schilder’s disease are unpredictable. For some individuals Schilder’s disease is progressive with a steady, unremitting course. Others may experience significant improvement and even remission. In some cases, Schilder’s disease is fatal ². Survival has been reported to be less than ten years after the onset ⁶. Patients with a good response to corticosteroids and those with smaller lesions may have a better prognosis. If the course is progressive, larger and larger patches of demyelination occur, interfering with motor movement, speech, personality, hearing and vision. Ultimately, the vital functions of respiration, heart rate and blood pressure are affected, leading to the individual’s death.

References

1. Schilder’s Disease. https://www.nationalmssociety.org/What-is-MS/Related-Conditions/Schilder-s-Disease
2. Schilder’s Disease Information Page. https://www.ninds.nih.gov/Disorders/All-Disorders/Schilders-Disease-Information-Page
3. Jarius S, Haas J, Paul F, Wildemann B. Myelinoclastic diffuse sclerosis (Schilder’s disease) is immunologically distinct from multiple sclerosis: results from retrospective analysis of 92 lumbar punctures. J Neuroinflammation. 2019;16(1):51. Published 2019 Feb 28. doi:10.1186/s12974-019-1425-4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396538
4. Schilder P. Zur Kenntnis der sogenannten diffusen Sklerose (über encephalitis periaxialis diffusa) Zeitschrift für die gesamte Neurologie und Psychiatrie. 1912;10:1–160. doi: 10.1007/BF02901445
5. Poser CM. Myelinoclastic diffuse sclerosis. Handbook of Clinical Neurology. New York, NY: American Elsevier; 1985. Vol 3: 419-428.
6. Treatments of Schilder’s Disease. https://www.nationalmssociety.org/What-is-MS/Related-Conditions/Schilder-s-Disease/Treatments