Neuro: White Matter Diseases

Demyelination vs. dysmyelination. 

Demyelination (adults): acquired disorder that affects normal myelin

Dysmyelination (children): inherited disorder affecting the formation or maintenance of myelin (rare) 

Dysmyelination:

1. Primary
   • ​​Multiple sclerosis
     • Age: 20-40 
     • Multiple CNS lesions separated in time & space
     • Histopath: inflammation (separates MS from other WM conditions such as PRES, osmotic myelinolysis), perivenular inflammation 
     • Location: 
       1. Periventricular white matter 
       2. Corpus callosum
       3. Cerbellum
       4. Spine
     • Perivenular, juxtacortical -> round/ovoid 
     • High T2 -> active inflammation or chronic scarring 
     • Enhancing & abnormal diffusion restriction = acute lesions
     • Subtype = tumefactive MS 
       • Large, conglomerate mass (can be difficult to differentiate from malignancy) 
       • Open ring enhancement -> leading edge of demyelination 
2. Ischaemic (OLD > 50 yrs)
   • ​​Deep white matter infarcts
     • ​Deep cerebral and periventricular white matter
       • Cortex, subcortical U fibres, corpus callosum, medulla, midbrain, cerebellar peduncles  are usually spared 
   • Lacunar infarcts 
     • 5-10 mm within basal ganglia (upper 2/3 of putamina) 
   • Vasculitis (sarcoidosis & lupus) 
   • Dissection 
   • Migrainous ischaemia 
   • Moyamoya disease 
   • CADASIL = cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy 
     • Inherited (notch3 mutation) 
     • Subcortical anterior temporal and medial frontal lesions (relatively specific) 
     • Presents middle age 

Prominent perivascular space can mimic deep whit matter/ lacunar infarcts -> u

3. Infectious

• ​​Progressive multifocal leukoencephalopathy
  • Immunocompromised 
  • Reactivation of latent JC virus 
  • Deep cerebral WM, subcortical U-fibres -> spares cortex and deep grey matter 
  • No mass affect, haemorrhage or contrast enhancement 
  • Coalesce 
• HIV encephalopathy 
  • Mild cerebral atrophy without focal abnormality
• Herpes encephalopathy 
  • Temporal lobes, insular cortex, subfrontal area and cingulate gyro 
  • Haemorrhage within area of involved parenchyma is strongly supportive of diagnosis
• ADEM 
  • Post-infective & post-vaccination -> viral illnesses approximately 2 weeks later
  • Children 
  • Multifocal or confluent WM lesions (can also involve grey matter) -> monophasic (compared to MS) 
  • Hursts disease = haemorrhagic subtype 
• Subacute sclerosing panencephalitis -> measles ((age 5-12) 
• Lyme disease 
• Neurosyphilis

4. Toxic & Metabolic

• ​​Central pontine myelinolysis
  • Characteristic demyelination of pons 
  • Patients with electrolyte abnormalities (children & alcoholics w malnutrition) 
  • Biphasic 
  • Rapidly evolving corticospinal syndrome with quadriplegia 
  • Also involves thalamus, BG
• PRES = posterior reversible encephalopathy syndrome 
  • Symmetric bilateral subcortical and cortical vasogenic oedema within the parietooccipital lobes 
• Marchiafava-Bignami disease (rare) 
  • Demyelination of the central fibres of the CC
  • Form of osmotic demyelination 
• Wernicke-Korsakoff syndrome (thiamine B1) 
  • Acute: High T2/enhancement of maxillary bodies, BG, thalamus & brainstem 
• Radiation injury 
  • History of radiotherapy 
• Toxic leukoencephalopathy -> chasing the dragon 
  • Symmetrical involvement
  • Subcortical u fibres spared
  • Butterfly wing pattern of cerebellar WM 

5. Dysmyelination​

• ​​​​​​Metachromatic leukodystrophy
• Adrenal leukodystrophy 
• Leigh disease 
• Alexander disease