Table 1

Recommended investigations in white matter disorders

Round 1 Identifying acquired causes
  • HIV test

  • Hepatitis B/C, syphilis

  • Vasculitic/autoimmune screen

  • Imaging with gadolinium of brain and spine

  • Lumbar puncture for routine constituents, cytology and JC virus

Round 2 Identifying metabolic causes
  • Very-long-chain fatty acids (X linked adrenoleukodystrophy)

  • White cell enzyme activity—galactocerebrosidase (Krabbe’s disease) and arylsulfatase A (metachromatic leukodystrophy)

  • Plasma amino acid profile and total homocysteine (methyltetrahydrofolate reductase deficiency and homocystinuria)

  • Plasma sterols and urine bile alcohols (cerebrotendinous xanthomatosis)

  • Endocrine screen

Round 3 Identifying genetic causes: re-evaluating the phenotype
  • Appropriate genetic testing—box 1

  • Imaging sensitive to calcification (eg, CT scan) and iron (eg, susceptibility-weighted MR)

  • Neurophysiology

  • Ophthalmology assessment including slit-lamp examination

  • Nerve/muscle biopsy

  • Brain biopsy in appropriate cases