Identification and outcomes of clinical phenotypes in amyotrophic lateral sclerosis/motor neuron disease: Australian National Motor Neuron Disease observational cohort.
To capture the clinical patterns, timing of key milestones and survival of patients presenting with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) within Australia.



Data were prospectively collected and were timed to normal clinical assessments. An initial registration clinical report form (CRF) and subsequent ongoing assessment CRFs were submitted with a completion CRF at the time of death.



Prospective observational cohort study.



1834 patients with a diagnosis of ALS/MND were registered and followed in ALS/MND clinics between 2005 and 2015.



5 major clinical phenotypes were determined and included ALS bulbar onset, ALS cervical onset and ALS lumbar onset, flail arm and leg and primary lateral sclerosis (PLS). Of the 1834 registered patients, 1677 (90%) could be allocated a clinical phenotype. ALS bulbar onset had a significantly lower length of survival when compared with all other clinical phenotypes (p<0.004). There were delays in the median time to diagnosis of up to 12 months for the ALS phenotypes, 18 months for the flail limb phenotypes and 19 months for PLS. Riluzole treatment was started in 78-85% of cases. The median delays in initiating riluzole therapy, from symptom onset, varied from 10 to 12 months in the ALS phenotypes and 15-18 months in the flail limb phenotypes. Percutaneous endoscopic gastrostomy was implemented in 8-36% of ALS phenotypes and 2-9% of the flail phenotypes. Non-invasive ventilation was started in 16-22% of ALS phenotypes and 21-29% of flail phenotypes.



The establishment of a cohort registry for ALS/MND is able to determine clinical phenotypes, survival and monitor time to key milestones in disease progression. It is intended to expand the cohort to a more population-based registry using opt-out methodology and facilitate data linkage to other national registries.
Neurosciences Department, University Hospital Geelong, Geelong, Victoria, Australia.
Paul
P
Talman
Center for Pattern Recognition and Data Analytics (PRaDa), Deakin University, Waurn Ponds, Geelong, Victoria, Australia.
Thi
T
Duong
St Joseph's Hospital Nomanby Road, Auburn, New South Wales, Australia.
Steve
S
Vucic
Calvary Healthcare Bethlehem Hospital Neuro-Consultancy, South Caulfield, Victoria, Australia.
Susan
S
Mathers
Center for Pattern Recognition and Data Analytics (PRaDa), Deakin University, Waurn Ponds, Geelong, Victoria, Australia.
Svetha
S
Venkatesh
Department of Neurology, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia Caulfield, Victoria, Australia.
Robert
R
Henderson
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
Dominic
D
Rowe
Department of Neurology, Flinders Medical Centre, Flinders Drive, Bedford Park, South Australia, Australia.
David
D
Schultz
Royal Perth Hospital, Shenton Park Campus Selby Street, Shenton Park, Western Australia, Australia.
Robert
R
Edis
Neurosciences Department, Fiona Stanley Hospital Murdoch, Western Australia, Australia.
Merrilee
M
Needham
Neurosciences Department, Austin Health Studly Road, Heidelberg, Victoria, Australia.
Richard
R
Macdonnell
Department of Neurology, University of Queensland Centre for Clinical Research and Royal Brisbane and Women's Hospital, Herston Road, Queensland, Australia.
Pamela
P
McCombe
Motor Neurone Disease Association of Australia, Australia.
Carol
C
Birks
Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Matthew
M
Kiernan
D000690:Amyotrophic Lateral Sclerosis / Q000145:classification / Q000401:mortality* / Q000628:therapy*; D001315:Australia; D018450:Disease Progression; D005260:Female; D005774:Gastrostomy / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use; D063087:Noninvasive Ventilation / Q000706:statistics & numerical data; D010641:Phenotype; D011446:Prospective Studies; D012042:Registries; D019782:Riluzole / Q000627:therapeutic use; D013997:Time Factors
D018696:Neuroprotective Agents; D019782:Riluzole
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