Alpers syndrome = poliodystrophia cerebri progressive
Alpers-Huttenlocher syndrome = infantile diffuse cerebral degeneration with hepatic cirrhosis

Thought to be a disorder of oxidative metabolism from mitochondrial dysfunction

AVOID VALPROIC ACID -> LIVER DYSFUNCTION!!!

Signs and symptoms

• Onset 1-3 years of age
• Sudden intractable seizures (GTC, focal, myoclonic)
• May begin as isolated seizures, status epilepticus, or epilepsia partialis continua
• Severe developmental delay, hypotonia, hemiparesis, ataxia, cortical blindness
• Hepatic failure, ascites, jaundice
• Mild axonal sensory neuropathy
• Abnormal pathology in spinal cord and peripheral nerves

Pathology/biochemistry/genetics

• Brain:
  • Neuronal loss, esp. olivary nuclei
  • Spongiform degeneration
  • Astrocytosis of visual cortex
• Liver:
  • Steatosis and fibrosis
  • Bile duct proliferation
  • Progression to severe cirrhosis
• Muscle biopsy:
  • Can show evidence of ragged-red fibers
• Genetic postulations:
  • Polymerase gamma gene (POLG) mutation
  • Mitochondrial DNA depletion
  • Prion disease - unlikely

Diagnostic tests

• Abnormal LFTs
• Elevated lactate
• CSF protein and lactate may be elevated
• Loss of VEPs
• EEG – slow wave activity with superimposed polyspikes. Increases with severity, into periods of burst-suppression
• CT – cerebral atrophy, hypodensity of cortex and white matter in occipital/posterior temporal lobes
• MRI – lesions in occipital lobes, caudate, thalamus. DWI changes in acute phase – may reverse
• MRS – high lactate in regions correlated with symptoms
• Muscle biopsy – ragged-red fibers, cyt-c negative fibers, and respiratory chain enzyme tests suggestive of mitochondrial disorder