Parent of origin effects in inherited MS

Herrera BM, Ramagopalan SV, Lincoln MR, et al.  Parent of origin effects in MS. Observations from avuncular pairs.  Neurology; 2008: 71:799-803.

 

Genetics review of MS.  The risk for a first degree relative of an MS proband of 3-5 % is 30-50 times higher than the general population (0.1%) and vary by relatedness and number of affected individuals in family.  There is agreement that there are a number of genes of small effect interacting with the environment. 

 

This study used avuncular pairs and found a strong predilection for maternal gene of origin in 871 families surveyed.  After removing families where the parent had MS, there were 807 families with 938 avuncular pairs.  There were 526 maternal pairs, and 412 paternal pairs which was highly significant (McNemar test).

 

Moreover, the niece to nephew ratio of 2.67:1 was higher than the aunt/uncle ratio of 1.85.  In paternal families only, the ratio was higher in families with an affected aunt. 

 

Authors note that in Canada the increase is MS is noted to be due to increased number of females. 

 

The gene of locus is not known.

 

Authors also note the May birthday peak and November birthday nadir for MS births.

Dalframpridine and trigeminal neuralgia

Birnbaum G., Iverson J.  Dalfampridine may activate latent trigeminal neuralgia in patients with multiple sclerosis.  Neurology 2014; 83: 1610-12.

Of 71 patients in MS clinic given dalfampridine, 5 had a history either of trigeminal neuralgia (TN) or altered facial sensation.  One with altered facial sensation developed TN after starting dalfampridine x 18 months.  Pain subsided when dalfampridine was stopped.  Three other patients had marked worsening of TN after starting dalfampridine, became refractory to medicinal treatment, and in one case required surgery for pain control

Moral- use dalfampridine with caution in patients with preexisting TN.

Aubagio and birth defects

Annette M. Langer-Gould, Neurology 83; 2014:1685.

response to a letter to editor.

Teriflunamide is the active ingredient of leflunomide.

Published literature has about 100 pregnancies with accidental exposure.  There were 56 live births from 64 women with an average of 3 weeks of postconception leflunomide exposure, of which 95 % underwent rapid elimination.  Three of 56 (5.4 %) had major structural defects , 47 % had 3 or more minor structural anomalies, and 35.7 % were delivered preterm.  Exposed infants were significantly smaller at birth and postnatally. 

Recommendation is that a woman on teriflunomide desiring pregnancy should stop medication untila  safe leflunomide level is reached either by natural elimination (approximately two years) or a rapdi elimination procedure.

based on Langer Gould AM.  The pill x 2: what every woman with multiple sclerosis should know.  Neurology 2014; 82: 654-655