Diagnosis and prognosis

Summary

There is currently no one diagnostic test for MND. Because of its relatively rare nature and non-specific symptoms, it is currently being diagnosed by an exclusion method. This means that physicians have to rule out a whole range of other neurological and muscular conditions by a variety of uncomfortable tests before giving a diagnosis of MND. Finding a simple and, preferably, a pain-free test that would make this process easier and faster, would likely increase effectiveness of existing and emerging treatments. These tests require searching for what is called a ‘biomarker’ – a signature of a biological change occurring in a specific disease (or a group of diseases). Some biomarkers have been identified for MND and are being tested to develop them into clinical tests.

Another reason to look for biomarkers is to keep track of the progression of the disease. Some people with MND experience a rapid progression, with only a few months from symptom onset to death. Others will progress at a much slower rate, living for several years from diagnosis. Knowing the likely rate of progression at the actual point of diagnosis would then provide a much clearer prognosis for each patient, and enable them to make more informed future decisions. Researchers are now testing various measures to see how these biomarkers might change as the disease progresses, and whether these differ in people with rapid progression from those with a slower progression rate.

More detail

There is a number of different ways that can help researchers in their search for biomarkers. These span from analysing biological fluids, such as blood, urine, or cerebrospinal fluid (CSF; cushioning fluid encasing the brain), through electrophysiology and neuroimaging methods, to neuropsychological pen-and-paper tests. However, despite having identified a few potential biomarkers, all of these are still in development.

And while having a test that would track physiological changes happening in the body is the ultimate goal, we can still measure how these changes reflect themselves in one’s functional abilities. So far, there is only one established method of assessing progression of MND and that is by using the ALS Functional Rating Scale (ALSFRS).

ALSFRSHunting for biomarkersFactors associated with clinical progression

ALSFRS is a clinical chart on which a physician records details about their patient’s functional abilities. The newest, revised, version (ALSFRS-R) consists of 12 items, each asking about specific abilities (such as speech, swallowing, dressing, or walking). Every item is rated on a 5-point scale ranging from ‘0’ to ‘4’, where ‘4’ represents normal functioning, and ‘0’ represents severe disability. A cumulative score (where ‘48’ marks normal functioning) gives the physician a considered view on the person’s disease status.

By completing these assessments regularly, the patient’s disease progression can be tracked. For example, on average, a person with MND loses 12 points a year, whereas someone with a more rapid progression could lose 20 points a year. The ALSFRS is also used as a measure of disease progression in clinical trials, which can help us to see if people receiving a trial drug are progressing slower than those receiving a placebo (dummy drug).

The following presentations will discuss the ALSFRS at the Symposium. Find their abstracts using the codes below in Abstracts online:

  • C41: How good is the respiratory subscore of ALSFRS-R?
  • C89: Biomarker mixtures predict ALSFRS-R at time of diagnosis.

The MND Association currently funds several research projects that are looking for specific biological changes in people with MND. These include a multi-centre project AMBRoSIA and Oxford-based project BioMOx. These biomarker projects are collecting samples from people with MND, as well as their family, and people unaffected by MND, to look for changes that could indicate that MND is present and progressing at the very early stages of the disease.

The following presentations will discuss biomarkers at the Symposium. Find their abstracts using the codes below in Abstracts online:

  • C45: Urinary p75 neurotrophin receptor extracellular domain: A biomarker relevant to ALS therapy development
  • C46: Blood and CSF neurofilament levels as biomarkers of pre-symptomatic disease
  • C63: Cortical dysfunction appears to be a regional feature in ALS
  • C78: Patterns of cortical atrophy in ALS and implications on prognosis

More abstracts relating to biomarkers can be found in sessions 6C, 7C, and 8C.

Aside from biofluid and neuroimaging markers that might reflect presence and progression of MND, researchers are also looking into factors such as speed of metabolism or levels of certain vitamins that might correlate (correspond) with ALSFRS scores. One of the talks presented at the Symposium will present findings that show that people with MND who have higher metabolic rate are likely to have a faster progression of functional decline. With these studies, however, it is important to know that these findings are not necessarily a simple cause and effect process; that is, when one thing often comes with another, we can label them as co-occuring (due to a certain factor), but we cannot simply assume that one thing causes the other.

The following presentations will discuss clinical progression at the Symposium. Find their abstracts using the codes below in Abstracts online:

  • C86: Hypermetabolism is associated with lower motor neurone burden, functional decline and predicts survival in ALS
  • C88: Clinical characteristics and associated factors in ALS patients with longer survival

More abstracts relating to clinical progression can be found in session 9B.