subacute combined degeneration of spinal cord; Lichtheim's disease; Putnam-Dana Syndrome

Etiology

• associated with vitamin B12 deficiency
  • NOT mitigated by folate supplementation
• also associated with
  • copper deficiency
  • nitrous oxide exposure

Epidemiology

• 80% of cobalamin-deficient patients with peripheral neuropathy

Pathology

• degeneration of dorsal, anterolateral, lateral columns of spinal cord
  • demyelination early
  • Wallerian degeneration in later stages
  • mid thoracic segments of the spinal cord affected most
• occasionally foci of perivascular demyelination in cerebral white matter
  • large ascending & descending tracts in internal capsule, the cerebellar peduncles & the pons tend to be spared
• astrocytosis & neuroglial scarring may occur

Clinical manifestations

• stage 1
  • paresthesias occur early; may preceed other abnormalities by months
  • gait ataxia may progess over a few weeks to over 1 year
  • spastic paraparesis
  • lower limbs generally affected before upper limbs
  • writing impairment may occur
• stage 2
  • severe ataxic paraplegia
  • anesthesia of the legs & trunk
  • may develop rapidly
• stage 3
  • complete paraplegia
  • total anesthesia
• may be associated with mental status changes (4-28%)
  • depression
  • confusion
  • amnesia (Wernicke's syndrome)
  • dementia
  • paranoid psychosis

Laboratory

• cerebrospinal fluid analysis
  • slightly increased protein
  • CSF vitamin B12 levels much less than serum levels
• serum chemistries consistent with vitamin B12 deficiency
  • vitamin B12 in serum is low
  • serum methylmalonic acid is high
  • serum homocysteine is high
• complete blood count (CBC) consistent with macrocytic anemia
  • MCV is high
  • hemoglobin in blood is low
• peripheral smear consistent with vitamin B12 deficiency
  • hypersegmented neutrophils & macrocytes

Radiology

• MRI of the cervical & thoracic spinal cord may show demyelination
  • in mid-thoracic region, zone of demyelination may extend around the spinal cord
  • in cervical region, posterior columns alone may show demyelination

Complications

• demyelination of the optic nerves has been described

Management

• vitamin B12 replacement
  • may halt progression of disease but generally does not reverse existing pathology
  • see vitamin B12 deficiency

More general terms

• neurodegenerative disease
• spinal cord disease

Additional terms

• lateral column
• posterior (dorsal) column
• vitamin B12 deficiency

Patient information

subacute combined degeneration of spinal cord patient information