Schilder's Disease

Synonyms: diffuse sclerosis, myelinoclastic diffuse sclerosis

Schilder's myelinoclastic diffuse sclerosis is a rare sporadic demyelinating disease that usually affects children between 5 and 14 years old. It was first described by Paul Schilder in 1912 as a severe and fulminating syndrome of acute demyelinating disease^[1]. There is widespread demyelination of both cerebral hemispheres with varying degrees of axonal injury.

The term diffuse cerebral sclerosis was originally used to identify a heterogeneous group of diseases affecting cerebral white matter. Most of the diseases previously classified as Schilder's disease are now classified as dysmyelinating leukodystrophies or are included within the spectrum of multiple sclerosis. Schilder's disease now appears to belong to a heterogeneous group of disorders which includes Krabbe's disease, sudanophilic cerebral sclerosis, metachromatic leukodystrophy and adrenoleukodystrophy^{[1, 2]}.

The diagnostic criteria established by Poser in 1985^[3]:

• One or two roughly symmetrical large plaques. Plaques are greater than 2 cm in diameter.
• No other lesions are present and there are no abnormalities of the peripheral nervous system.
• Results of adrenal function studies and serum very long chain fatty acids are normal.
• Pathological analysis is consistent with subacute or chronic myelinoclastic diffuse sclerosis.

Epidemiology

Schilder's disease is very rare.

Presentation

• The onset of illness is usually subacute, but may be more sudden.
• It often occurs shortly after an infectious illness. It may start with headache, malaise and fevers.
• A wide variety of neurological abnormalities may occur, including aphasia, memory disturbances, irritability, confusion, disorientation, and behavioural disturbances. Patients may appear to be psychotic.
• Deafness is common. Other brainstem or cerebellar deficits include vertigo, paralysis of eye movements, nystagmus, facial palsy, dysarthria or dysphagia. Peripheral cranial nerve abnormalities may occur, including optic neuritis and optic atrophy.
• Cortical blindness is common. Hemiparesis or cortical sensory deficits may occur.
• Malnutrition and cachexia are commonly reported in the later chronic stages of illness.

Differential diagnosis

• It often mimics intracranial neoplasm or abscess^[4].
• Viral encephalitis or viral meningitis, subacute sclerosing panencephalitis (SSPE), progressive rubella panencephalitis, brucellosis.
• Churg-Strauss syndrome.
• Glioblastoma multiforme.
• Multiple sclerosis.
• Granulomatosis with polyangiitis.
• Adrenoleukodystrophy.
• Primary CNS vasculitis.
• Sarcoidosis.

Investigations

• Serum very long chain fatty acid studies and adrenal function studies must be normal; otherwise a diagnosis of adrenoleukodystrophy is suggested.
• EEG: abnormalities such as periodic lateralised epileptiform discharges suggest the alternative diagnosis of SSPE or progressive rubella panencephalitis.
• Lumbar puncture:
  • CSF may be normal or may contain lymphocytes and monocytes.
  • Mild to moderate elevation of CSF protein is often found.
  • Elevation of CSF IgG is found in 50-60% of cases. CSF abnormalities on the CSF immune profile, such as oligoclonal bands or elevation of the CSF serum IgG index or CSF IgG synthetic rate, further suggest SSPE or progressive rubella panencephalitis.
  • Ruling out an infectious aetiology is essential: this includes viral cultures of CSF, nasal or oropharyngeal secretions, and rectal swab. Acute titres to be assayed should include Brucella spp; Bartonella spp; Ebstein-Barr virus, cytomegalovirus, Mycoplasma spp. and herpes viruses.
• MRI: demonstrates one or two large confluent lesions in the deep white matter, usually the centrum semiovale. Additional lesions in the brain or spinal cord may imply multiple sclerosis, acute disseminated encephalomyelitis or some other alternative diagnosis.
• Sequential EEG studies: show progressive deterioration in background organisation, with predominantly high-voltage irregular slowing. Periodic lateralising discharges or other pseudo-rhythmical high-voltage discharges suggest the diagnosis of SSPE^[5].
• Brain biopsy specimens may be required to exclude infection, tumours, and vasculitic or other inflammatory processes.

Management

• Corticosteroids may be effective in some patients^[6].
• There is no information regarding the efficacy of immunomodulatory therapy in Schilder's disease as defined by the strict criteria established by Poser^[5].
• Management is mainly supportive, including physiotherapy, occupational therapy and nutritional support in the later stages.

Complications

• Cerebral herniation.
• Development of pneumonia, sepsis, pulmonary embolisation, skin breakdown and ulceration in individuals who are immobile and bed-bound.
• Complications due to corticosteroids.

Prognosis

• Only nine patients who fit the tightly defined diagnosis of diffuse sclerosis have been reported. In these patients, deterioration has been constant and usually rapid with death within five years.
• In those categorised by Poser in 1957 as having transitional sclerosis, the mean duration of survival was reported as 6.2 years after onset. Disease duration was less than one year in 40% of cases^[3].
• Pre-pubertal cases, those with a good response to corticosteroids and those found to have smaller lesions may have a better prognosis.