Metabolic, Toxic, Inflammatory Brain Disorders

Question 1

In neurometabolic diseases, brain injury and clinical symptoms result from:

Answer 1

• Lack of production of a necessary biochemical
• Formation of abnormal biochemical that is toxic
• Usually fetal
• Occasionally maternal

Question 2

Neurometabolic disease typically manifest when?

Answer 2

After birth (because the placenta usually removes toxins and supplies necessary chemicals)

Question 3

How and when can neurometabolic diseases present and why?

Answer 3

• Earlier (neonatal/infantile) if enzymatic changes are profound.
• Later (juvenile/adult) if enzymatic changes are less profound

Question 4

Why are metabolic, toxic, and inflammatory changes lumped together?

Answer 4

Toxins - whether endogenous metabolic or exogenous (ie alcohol/cocaine, etc) interfere with normal brain metabolism in similar ways. Inflammatory conditions (autoimmune, chemo, radiation) - can also have similar histologic changes.

Question 5

What are presenting symptoms in MTI brain disorders?

Answer 5

• nonspecific - may be acute, subacute, slowly progressive and include hypotonia, seizures, spasticity, ataxia, movement disorder, delay in achieving developmental milestone, focal neurologic deficit.

Question 6

Is imaging typically diagnostic in disorders of MTI?

Answer 6

• No - suggestive, but not diagnostic.
• biochemical/genetic tests are often also not diagnostic
• more than 60% don’t get an exact diagnosis
• Even with an exact diagnosis, prognosis may be uncertain.

Question 7

When should imaging be performed for question of MTI disease?

Answer 7

• Early on in the disease process. Although if too early, may be too subtle and you won’t see anything
• If too late - abnormalities may progress to nonspecific/diffuse pattern such as global white matter injury.
• Follow up studies can be performed with disease progression.
• If possible during active/flare up - which may show increased metabolites/diffusion restriction for instance vs. a more chronic phase of the disease (when diffusivity is increased and metabolite levls are lower or return to normal

Question 8

Which sequences should be performed for MTI disease?

Answer 8

• Anatomic MRI
  
  • T1 for myelination pattern in first year
  • T2 for meylination pattern/white matter injury after first year (T1 can still be used in cases of discrepancy)
  • T2/FLAIR - after completion of myelination (1-2yrs) is best to detect WM injury
• DWI
• Spectroscopy

Question 9

What are types of WM injury in TMI disorders?

Answer 9

1. Hypomyelination
2. Demyelination
3. Myelin Vacuolization
4. Cystic Degeneration