Pain and Temperature sensation are carried by the spinothalamic tract.  They decussate immediately in the spinal cord.

Vibration and Proprioceoption are carried by the posterior columns.  They ascend on the ipsilateral side of the spinal cord and decussate in the medulla (brain stem).

Interpretation of Vitamin B12 Levels:

• > 300 pg/mL = NORMAL RESULT; vitamin B12 deficiency unlikely (sensitivity ~90%)
• 200 – 300 pg/mL = BORDERLINE RESULT; vitamin deficiency possible
• < 200 pg/mL = LOW RESULT; consistent with vitamin B12 deficiency (specificity 95-100%)

* If patient has BORDERLINE RESULT, but a high degree of suspicion for B12 or folate deficiency – check methylmalonic acid and/or homocysteine.

Interpretation of MMA and HC Levels:

• Vitamin B12 deficiency – BOTH ARE ELEVATED
• Folate deficiency – Homocystein is ELELVATED, while MMA is NORMAL

*Folate does not participate in MMA metabolism, but B12 is needed for both.

Clinical Manifestations of B12 Deficiency:

Hematologic

• Macrocytic anemia (megaloblasic if folate also low)
• Pancytopenia

Neurologic

• Paresthesias
• Peripheral neuropathy
• Subactue combined degeneration (demyelination of dorsal columns and corticospinal tract)

Psychiatric

• Irritability, personality changes
• Mild memory impairment => dementia
• Depression
• Psychosis

Cardiovascular

• Possible increased risk of MI (due to elevated homocysteine)

Vitamin B12 Absorption:

Step 1: acidic stomach breaks down B12 from food.
Step 2: intrinsic factor (IF), released from parietal cells, binds B12 in the duodenum.
Step 3: IF-B12 complex is absorbed by the terminal ileum.
Step 4: Once absorbed, B12 binds to transcobalamin II and is transported throughout the body.

Pernicious Anemia:

• Type of autoimmune disease that leads to destruction of gastric parietal cells.
• Destruction of these cells leads to decreased production of intrinsic factor, and therefore, limits B12 absorption.

Testing for Pernicious Anemia:

• Parietal cell antibodies (85-90% sensitive) – but non-specific (occurs in other autoimmune states)
• Intrinsic factor antibody (50% sensitive) – but far more specific for diagnosis of pernicious anemia
• Schilling Test: not routinely used given superior sensitivity of HC and MMA and difficulty with radiolabeled reagents
  • Stage 1: radiolabeled B12 is administered orally and 24-hour urine is measure for B12 excretion
  • Stage 2: (performed if stage 1 is abnormal) radiolabeled instrinsic factor and B12 are administered orally and another 24-hour urine is collected.

Treatment of B12 Deficiency:

• Oral and parental B12 repletion are both potential options for treatment
• Studies have shown that high dose oral B12 is as effective as parenteral therapy through a secondary pathway that does not require IF or a functioning terminal ileum
• Treat B12 before folic acid to avoid precipitating subacute combined degeneration (giving folate first will turn the remaining B12 into methylcobalamin)