The NEALS primary lateral sclerosis registry

Abstract

Background and objective

Primary lateral sclerosis (PLS) is a neurodegenerative disease characterized by progressive upper motor neuron dysfunction. Because PLS patients represent only 1 to 4% of patients with adult motor neuron diseases, there is limited information about the disease’s natural history. The objective of this study was to establish a large multicenter retrospective longitudinal registry of PLS patients seen at Northeast ALS Consortium (NEALS) sites to better characterize the natural progression of PLS. Methods: Clinical characteristics, electrophysiological findings, laboratory values, disease-related symptoms, and medications for symptom management were collected from PLS patients seen between 2000 and 2015. Results: The NEALS registry included data from 250 PLS patients. Median follow-up time was 3 years. The mean rate of functional decline measured by ALSFRS-R total score was −1.6 points/year (SE:0.24, n = 124); the mean annual decline in vital capacity was −3%/year (SE:0.55, n = 126). During the observational period, 18 patients died, 17 patients had a feeding tube placed and 7 required permanent assistive ventilation. Conclusions: The NEALS PLS Registry represents the largest available aggregation of longitudinal clinical data from PLS patients and provides a description of expected natural disease progression. Data from the registry will be available to the PLS community and can be leveraged to plan future clinical trials in this rare disease.

Keywords:

• PLS
• upper motor neurons
• outcome measures
• survival
• disability

Acknowledgments

The authors thank all study participants and their families and caregivers for their dedication and contribution to MND research.

Declaration of interest

Sabrina Paganoni has received research funding from Target ALS, Harvard NeuroDiscovery Center, MGH ALS Therapy Fund, the Salah Foundation, the Spastic Paraplegia Foundation, Amylyx Therapeutics, Revalesio Inc., the ALS Association, ALS Finding a Cure, the American Academy of Neurology.

Fabiola De Marchi: reports no disclosures.

James Chan reports no disclosures.

Sara K. Thrower reports no disclosures.

Nathan P. Staff has received research funding from National Institutes of Health (CA 211887), Minnesota Regenerative Medicine Partnership (RMM 11215 CT002), Target ALS Foundation; serves as co-investigator on clinical trials by Brainstorm Therapeutics, Orion Pharmaceuticals.

Neil Datta reports no disclosures.

Yaz Y. Kisanuki reports no disclosures.

Vivian Drory reports no disclosures.

Christina Fournier received research support from Mallinckrodt, Amylyx Pharmaceuticals, Neuraltus Pharmaceuticals, and Cytokinetics. Dr. Fournier received research funding from the U.S. Department of Veterans Affairs Office of Research and Development (IK2CX001595-02).

Erik P. Pioro has received clinical trial and research funding from NIH/CDC, ALS Association, Iron Horse Diagnostics, Inc., and serves as consultant to Avanir Pharmaceuticals, Inc., Cytokinetics, Inc., ITF Pharma, Inc., MT Pharma America, Inc., and Otsuka America, Inc.

Stephen A. Goutman receives funding from NIH/NIEHS (K23ES027221), CDC/ATSDR, Target ALS, the ALS Association.

Nazem Atassi consulted for MT Pharma, Neuropore, Chronos, Boston Pharmaceuticals, Denali, GSK, Anelixis. He currently works for Sanofi-Genzyme.

Additional information

Funding

This study was supported in part by the Fund for Primary Lateral Sclerosis Research and Care at Massachusetts General Hospital.