A tuft of hair in the lumbosacral region is consistent with spina bifida occulta, a neural tube defect (NTD). NTDs are commonly associated with folate deficiencies. Valproate is a folate antagonist, thus contributing towards the development of spina bifida occulta.
NTDs result when the neuropores fail to fuse during week 4 of embryogenesis. The abnormality is associated with low folic acid intake during pregnancy, reduced folic acid absorption, or impaired enzymatic pathways involving folate, sometimes caused by drugs including methotrexate and the antibiotics trimethoprim/sulfamethoxazole (or Bactrim).
The 3 important types of NTDs for the USMLE Step 1 are:
1. spina bifida occulta (least severe, dura intact, no herniation)
2. spina bifida with meningocele (meninges herniate through defect and form CSF-filled sac, but spinal cord remains in spinal canal)
3. spina bifida with meningomyelocele (meninges and spinal cord herniate through defect)
Lin et al. review the use of folic acid supplementation during pregnancy: Current guidelines by the US Preventative Services Taskforce (USPTF) recommend that all women trying to conceive should take a daily supplement of 0.4-0.8 mg of folic acid. Considering that half of the pregnancies in the US are unplanned, the USPTF expanded their recommendation to cover all women of childbearing age, capable of getting pregnant.
Whitehead et al. discuss the genetic basis for NTDs. They found that patients with NTDs were more likely to be homozygous for the thermolabile form of 5,10 methylenetetrahydrofolate reductase, an enzyme important in homocysteine metabolism. Folic acid supplementation can help overcome a partial block in the conversion of 5,10 methylenetetrahydrofolate to 5 methyltetrahydrofolate, thus preventing the developing of NTDs.
Figure A shows spina bifida occulta in a transverse section through the spinal column.
Figure B shows myelomeningocele, although it cannot be distinguished from meningocele based on visual inspection alone.
Figure C shows the three types of neural tube defects (spina bifid a occulta, meningocele, and meningomyelocele.)
Answer 1: Chloramphenicol is a bacteriostatic antibiotic that targets the 50S ribosomal subunit used infrequently to treat H. influenza and bacterial meningitis. It is contraindicated in pregant women because it may cause "gray baby syndrome."
Answer 2: Gentamicin is an aminoglycoside antibiotic contraindicated in pregant women because it is ototoxic to the fetus.
Answer 3: Lithium is used in the treatment of bipolar disorder. It is contraindicated in pregnant women because it may cause Ebstein's anomaly (tricuspid valve abnormality) in the fetus.
Answer 5: Folic acid is recommended for pregnant women and women who expect to become pregnant to prevent NTDs in the neonate.
Lin KW, Birmingham E. Folic Acid for the prevention of neural tube defects. Am
PMID:21166375 (Link to Abstract)
Whitehead AS, Gallagher P, Mills JL, Kirke PN, Burke H, Molloy AM, Weir DG, Shields DC, Scott JM. A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects. QJM. 1995 Nov;88(11):763-6.
PMID:8542260 (Link to Abstract)
USMLE World Step 1 QBank Question #507. Copyright © USMLEWorld, LLC 2012