Leukoencephalopathy (white matter disease)

Diseases, , , ,

Damage to white matter may occur due to may conditions that can affect the brain. The clinical features, prognosis and treatment are related to the underlying condition

Clinical features:

There is a wide range of symptoms:

  • Rapidly progressive dementia/subacute encephalopathy, lower body parkinsonism/gait apraxia, behavioural changes, pseudobulbar speech and pseudobulbar affect may occur
  • Later on the patient is: akinetic mute, spastic quadraparesis
  • Earlier on focal signs may occur and give clues to the diagnosis e.g. peripheral neuropathy, occular movement abnormalities, seizures, myoclonus
  • Systemic features may give clues to the diagnosis: skin changes, systemic disease, e.g. significant hypertension, liver disease in Zellwegar disease,

Findings on Investigations:

+MRI:

  • Diffuse white matter involvement with or without grey matter involvement
  • May be symmetric, asymmetric, enhancing, nonenhancing, associated with hemorrhage or not, associated with DWI restriction or not,
  • May be anterior predominant, posterior predominant, involve or spare the U-fibers
  • May also involve the grey matter
  • In late stages atrophy occurs with gliosis
  • Helps guide DDx & further tests

Grading:

Fazekas grade I, Mild: few small punctate lesions in the white matter.
Fazekas grade II, Moderate: larger white matter lesions that are beginning to become confluent.
Fazekas grade III, Severe: confluent T2 hyper intensity.

Investigations to consider: consider as appropriate

MRI: guides further tests
MRA, CTA, Catheter angiography: as necessary if vasculopathy/vasculitis/cerebral vasoconstriction syndrome is considered
Lumbar puncture for CSF analysis:

  • Cell count, protein, glucose, IgG index, oligoclonal bands, myelin basic protein
  • Microscopy and Cultures
  • Broad tests for infections and inflammation, including viral encephalitis and other encephalitis
  • Features of inflammatory disease (autoimmune encephalitis, multiple sclerosis, ADEM, infectious disease) vs. non-inflammatory profile

Urine toxicology: cocaine, heroin
Serum toxicology
Carboxyhemoglobin: high in CO poisoning
Testing for infections:

  • VDRL, syphilis testing, Lyme disease testing,
  • HSV testing, West Nile virus testing (grey matter involvement initially), CMV testing, HIV testing, see viral encephalitis,
  • Cryptococcus testing, coccidiodes testing

Vasculitis screen:

  • ESR, CRP, ANA screen, ENA panel (anti- dsDNA, anti-Sm, anti-RNP, SSA, SSB, anti-Jo-1, antitopoisomerase ‘formerly anti Scl-70’, antinucleolar, anticentromere), ANCA (c-ANCA, p-ANCA), Complement C3, C4 and CH50

Testing for autoimmune or paraneoplastic encephalitis/encephalopathy:

  • anti: Hu (ANNA-1), Yo/PCA1, Ri, MaTa, CV2/CRMP5, amphiphysin, LGI1, CASPR2, VGKC, NMDA (NR1) and GAD65
  • Anti-TPO antibodies

Testing for CADASIL, NOTCH3 mutation
EEG:

  • May provide clues e.g. GPEDs in SSPE,

Tests for mitochondrial disease:

  • Muscle biopsy with biochemical and respiratory chain analysis and electron microscopy
  • Specific testing for individual mitochondrial disease e.g. MELAS, POLG mutation, etc

Selected testing for leukodystrophies:

  • X-linked adrenoleukodystrophy, Metachromatic leukodystrophy, Globoid-cell leukodystrophy (Krabbe’s disease)

Selected testing for perioxisomal disorders:

  • Zellweger disease,

Catheter angiography: if vasculitis is suspected
Brain biopsy

Causes of leukoencephalopathy (diffuse white matter disease):

Vascular:

Infectious:

Inflammatory:

Paraneoplastic:

Neoplastic:

Toxic and drug induced:

Metabolic:

 

References:

  • Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol. 1987 Aug;149(2):351-6.

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