New diagnostic criteria for ALS offer more certainty in clinical practice and trials

Neurodegenerative disorders

By Mardi Chapman

19 Aug 2021

The simplified ‘Gold Coast’ criteria for the diagnosis of amyotrophic lateral sclerosis (ALS) should be implemented into clinical practice and clinical trial settings, its developers say.

According to an opinion article in Muscle & Nerve, authored by an international team including Australians Professor Steve Vucic and Professor Matthew Kiernan, the Gold Coast criteria merged four diagnostic categories from previous models into a single ‘presence of ALS’ entity.

The criteria, established at an international consensus meeting held on the Gold Coast in 2019, has also been tested retrospectively in a cohort of more than 500 Australians with suspected ALS attending two major ALS centres in Sydney.

The study, published early this year in Annals of Neurology, confirmed 350 cases of ALS after “extensive clinical, laboratory, neuro-physiological, and radiological assessment” including >6 months follow-up for evidence of progression.

The study found the sensitivity of the Gold Coast criteria (92%) was comparable to the Awaji (90.3%; p = 0.39) and revised El Escorial (88.6%; p = 0.15) criteria.

The specificity of the Gold Coast criteria also remained high (88.5%), although it was lower than that of the Awaji (95.5%) and rEEC criteria (96.2%).

“The diagnostic utility of the Gold Coast criteria was maintained irrespective of functional status, disease duration or site of disease onset,” the Muscle & Nerve article said.

The Gold Coast criteria also effectively excluded people with primary lateral sclerosis (PLS).

The authors said the Gold Coast criteria had demonstrated clinical utility.

“Importantly, clinical utility may be evident even in the absence of effective therapies, in that diagnostic uncertainty is resolved, thereby enabling patients and their carers to plan and cope with the illness.”

“As such, earlier diagnosis may lead to improvement in daily functioning and quality of life in ALS patients, as well as better outcomes in some clinical trials.”

“Furthermore, patients will be prevented from undergoing unnecessary additional investigations, thereby reducing any further burden.”

Speaking to the limbic, Professor Steve Vucic from Westmead Hospital and the University of Sydney, said the previous diagnostic categories were confusing and didn’t have much meaning.

For example, someone diagnosed with “possible ALS” definitely had ALS but it just took longer to get to the more progressive form of the disease.

“In addition to being a lot simpler to apply, it also looks at the forms of ALS, which we all know are ALS but we can’t diagnose with the older criteria…lower motor neuron variants or progressive muscular atrophy variants,” he said.

Professor Vucic said other trials testing the new criteria were coming from China and Europe.

“I think with more trials coming out, people will be more comfortable with the criteria. It’s a very simple criteria which reflects clinical practice.”

“It lends itself well to implementation in a clinical setting and a clinical trials setting because it is the ALS physicians who are selecting patients to go into clinical trials.”

“I think what really needs to be done is to do a prospective, multicentre study looking at a number of things – not only sensitivity and specificity but its reliability. For example, how easy is it for a neurologist that does not specialise in ALS necessarily? How easy is it for them to implement the criteria?”

He said clinicians certainly don’t want to do is miss anything that could be treated such as demyelinating motor neuropathies which can be managed with immunotherapy.

However he said people wanted diagnostic certainty for a number of reasons.

“We want to give patients a firm diagnosis so they can plan and we can institute the current treatments that we have. They are not very effective but they are there and can slow down disease progression.”

“We can institute non-pharmacological measures such as referral to a multidisciplinary clinic where issues pertaining to swallowing and speech can be addressed. These things definitely improve quality of life.”

“But we also want to give certainty to recruitment of patients into clinical trials at a very early stage in the disease process. What we know now from a number of failed trials and some that have been partially successful is that if you get the patients very early and select a cohort of patients that progress at a rate you would expect they progress, we will find more effective therapies at least initially in slowing disease progression.”

“But our hope is if we can get these patients into the trials very early on that we will be able to do something for the course of the disease.”

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