Matthew Kiernan, MBBS, PhD, DSc, FRACP, FAHMS, University of Sydney, Sydney, Australia, shares an overview of recent advances in the diagnosis of amyotrophic lateral sclerosis (ALS). Previous diagnostic criteria categorized patients as definite, probable, possible, or suspicious, based on diagnostic certainty. The newly established Gold Coast criteria has eliminated these subsets and instead provided possible outcomes of either ALS or not ALS, to facilitate earlier diagnosis, enable clinical trial participation, and improve inter-rater agreement. The Gold Coast criteria for diagnosis of ALS requires evidence of progressive motor impairment, presence of upper and lower motor dysfunction, and investigations to exclude other disease processes. Prof. Kiernan additionally talks on the diagnostic utility of cortical hyperexcitability assessed by transcranial magnetic stimulation (TMS) in ALS. The presence of cortical hyperexcitability together with a fitting clinical phenotype can support the definitive diagnosis of ALS, and thus, work is ongoing to develop a protocol to make this technique widely accessible. This interview took place at the American Academy of Neurology 2022 Congress in Seattle, WA.
Transcript (edited for clarity)
So in our clinic, we use TMS to study all of our patients and we find it very helpful. If you see cortical hyperexcitability, it matches the clinical phenotype and we can be sure that is ALS. With the technology, this has been built up from scratch in a research setting and the next major challenge for us is to make this commercially available. So we’re dealing with industry partners, and we’re trying to make a protocol that someone can just buy off the shelf, all the hardware and the software, and be able to use it diagnostically in their own clinic...
So in our clinic, we use TMS to study all of our patients and we find it very helpful. If you see cortical hyperexcitability, it matches the clinical phenotype and we can be sure that is ALS. With the technology, this has been built up from scratch in a research setting and the next major challenge for us is to make this commercially available. So we’re dealing with industry partners, and we’re trying to make a protocol that someone can just buy off the shelf, all the hardware and the software, and be able to use it diagnostically in their own clinic. And until it’s user friendly and freely available, we won’t be able to see it in many centers, but with the award of the Sheila Essey prize, I hope to use those funds to try and drive the commercialization and availability of these techniques.
So in the past, the diagnosis of ALS has often been used as a diagnosis of exclusion. So people would say, “It could be this, it could be that,” and they wouldn’t actually actively diagnose the condition. There was a feeling that if you did diagnose it, what’s the point anyway? We can’t offer anything. But now, we know that we do have therapies, including riluzole, we’ve got multidisciplinary care, respiratory support. And the quicker we diagnose patients, the more neuroprotection we can give, so the better off patients will be in a clinical trial setting. To that end, we were also involved in the establishment of new guidelines for ALS, the Gold Coast criteria. And criteria for the diagnosis of ALS date back to the El Escorial criteria meeting of the World Federation of Neurology, subsequently the Airlie House criteria and the Awaji criteria.
With these criteria, they used a stratification approach, so whether the disease was definite, probable, possible or suspicious. What we’ve done is taken all of those categories out and we said that ALS by definition, is a progressive impairment of the motor system. So if it’s not progressive, it’s not ALS. Secondly, there has to be evidence of upper and lower motor neuron abnormalities on clinical presentation. And lastly, other conditions are excluded through appropriate investigations. We know that when clinicians, neurologists diagnose ALS, they’re about 95, 96% accurate. So by simplifying these diagnostic criteria, we’re making it a binary decision, that is, it is either ALS or it isn’t, rather than these sort of unusual probable, definite, etc. And through this, we hope to basically enroll far more patients into clinical trials.