Three Major Controversies in Neurology: A Debate

Bret S. Stetka, MD

Disclosures

May 18, 2015

In This Article

On Thursday, April 23, at the American Academy of Neurology annual meeting in Washington, DC, six doctors took the stage in pairs to debate three ongoing controversies in neurology.[1] Speakers were each given 10 minutes to argue their side, as well as a 3-minute rebuttal, after which the audience was asked to pick a side by raising their hands. Below is a summary of the session, along with the moderator's eyeball estimates of the final vote counts.

Gene-Sequencing in Neurology: Yea

The controversies session started off with a back and forth on whether or not whole-exome sequencing is ready for the neurology clinic. The exome is the portion of the genome that encodes for proteins. And given that 85% of known disease-causing gene variants reside here, exome sequencing can offer a wealth of genetic information of value to clinical research. But given current therapies for neurologic illness, is it of value to the clinician?

Christine Klein, MD, of the University of Lübeck in Lübeck, Germany, feels that it is. "When it comes to whole-exome sequencing, the future has already begun," she started off. Dr Klein then reviewed what technologies are available and their costs. Single-gene sequencing runs between $500 and $2000, and targeted gene panels are somewhere in the range of $1500-$4000. Exome sequencing costs about $5000; however, considering the fact that clinicians often order multiple single-gene tests or panels, in many cases sequencing the exome might be the most economical approach.

Dr Klein used a case to illustrate the point that though numerous neurologic disorders associated with certain genetic variants can be diagnosed clinically, in reality they're often not, and diagnosis can be delayed for years. In these cases, exome sequencing could result in earlier diagnosis and treatment. A study[2] published in JAMA tested 814 patients with suspected but unknown inherited diseases. Using exome sequencing, 26% of the diagnoses were clarified. Better still were findings from recent work showing that whole-exome sequencing can clarify the diagnosis in patients with unknown ataxias 64% of the time, compared with just 18% of the time using targeted next-generation single-gene sequencing.[3]

Also supporting the utility of exome sequencing is the possibility of reverse phenotyping, in which knowing the genetic variant allows clinicians to reconsider and inform the clinical picture and approach.

Klein then pointed out that while the idea of more extensive gene sequencing can be overwhelming, we should look at it in light of the fact that by the year 2018, newborn gene panels will be screening for 84 diseases—so why not go a step further? She also compared the reluctance around the young technology to the rise of MRI some years ago, at which time many predicted that the neurologist would become dispensable. "I think we all know that this is not the case," Klein commented. "In fact, neurologists have probably benefited the most because of these developments."

Perhaps Klein's best argument in support of exome sequencing is the prediction that technology could bring down healthcare costs: It's a once-in-a-lifetime test, it's relatively noninvasive, and its price has been steadily declining.

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