Employing prospectively collected and existing observational data from within the Cleveland Clinic and from external sources, our work has addressed various aspects of amyotrophic lateral sclerosis (ALS) phenomenology, natural history and treatment valuation. Cognitive impairment, emotional change, and apathy are increasingly recognized manifestations of the disease. Using patient-reported outcomes obtained from patients followed at Cleveland Clinic through the Knowledge Program, we have studied neuropsychiatric manifestations of ALS including depression and pseudobulbar affect, and estimated quality of life by disease stage. Analyzing extensive functional impairment measures from the PRO-ACT dataset that includes observations from numerous clinical trials, we have examined patterns of progression of disease, proposed a novel staging methodology, and developed a framework for assessing cost-effectiveness of ALS treatments. This work is valuable for clinical trial design as well as understanding natural history. The need to measure the value of treatments is especially acute with novel treatments. We have also worked on mechanistic modeling of propagation of neurodegeneration in ALS progression that may offer insights into pathophysiology. We are also examining ethical aspects of treatment decisions in ALS. Our group includes individuals with diverse skillsets (clinical trial experience, expertise in quantitative methods, as well as fluency with ethical principles) that are well suited to ask and answer meaningful questions relevant to this complex and refractory disease.

Contact person:

Nimish Thakore





Lapin B, Mate K, Li Y, Thakore N. Subjective health perception prioritizes psychological well-being over physical function in advanced ALS: A multigroup structural equation modeling analysis. J Neurol Sci. 15;442:120442, 2022.  doi: 10.1016/j.jns.2022.120442.

Thakore NJ, Pioro EP. Letter to editor. Amyotroph Lateral Scler Frontotemporal Degener. Oct 26;1-2, 2022. doi: 10.1080/21678421.2022.2136995.

Thakore NJ, Lapin BR, Mitsumoto H. Early initiation of riluzole may improve absolute survival in amyotrophic lateral sclerosis. Muscle Nerve. 66(6):702-708, 2022. doi: 10.1002/mus.27724.

Thakore NJ, Drawert BJ, Lapin BR, Pioro EP. Progressive arm muscle weakness in ALS follows the same sequence regardless of onset site: use of TOMS, a novel analytic method to track limb strength. Amyotroph Lateral Scler Frontotemporal Degener. 22(5-6):380-387, 2021. doi: 10.1080/21678421.2021.1889000

Thakore NJ, Pioro EP, Udeh BL, Lapin BR, Katzan IL. A cost-effectiveness framework for amyotrophic lateral sclerosis, applied to riluzole. Value in Health 23(12): 1543-1551, 2020. doi: 10.1016/j.jval.2020.06.012

Thakore NJ, Lapin BR, Pioro EP: Stage-specific riluzole effect in amyotrophic lateral sclerosis: a retrospective study. Amyotroph Lateral Scler Frontotemporal Degener. 21(1-2):140-143, 2020. doi: 10.1080/21678421.2019.1655060

Thakore NJ, Lapin BR, Pioro EP, Aboussouan LS: variation in noninvasive ventilation use in amyotrophic lateral sclerosis. Neurology 93(3):306-316, 2019. doi: 10.1212/WNL.0000000000007776

Deconstructing progression of amyotrophic lateral sclerosis in states: a Markov modeling approach. Thakore NJ, Lapin BR, Kinzy TG, Pioro EP. Amyotroph Lateral Scler Frontotemporal Degener. (Published online June 12, 2018, doi: 10.1080/21678421.2018.1484925)

Trajectories of impairment in amyotrophic lateral sclerosis: Insights from the Pooled Resource Open-Access ALS Clinical Trials cohort. Thakore NJ, Lapin BR, Pioro EP. Muscle Nerve. 57(6):937-945, 2018. doi: 10.1002/mus.26042

Laughter, crying and sadness in ALS. Thakore NJ, Pioro EP. J Neurol Neurosurg. 88:825-3, 2017. doi:10.1136/jnnp-2017-315622.

Depression in ALS in a large self-reporting cohort. Kawada T, Thakore NJ, Pioro EP. Neurology. 97:1631-1632, 2016. doi: 10.1212/01.wnl.0000503501.75283.f1

Depression in ALS in a large self-reporting cohort. Thakore NJ, Pioro EP. Neurology. 86:1031-8, 2016. doi: 10.1212/WNL.0000000000002465.

Members and Collaborations

Members and Collaborations

Within Cleveland Clinic

  • Rebecca Kuenzler, MD
  • Brittany Lapin, PhD, MPH
  • Loutfi Aboussouan, MD
  • Danielle Richards, MD

Collaborations outside Cleveland Clinic

  • Hiroshi Mitsumoto, MD (professor of Neurology, Columbia University, New York, NY)
  • Erik Pioro, MD (Professor of Neurology, University of British Columbia, Vancouver, BC, Canada)
  • John Ravits, MD (Professor of Neurology, University of California, San Diego, CA)
  • Linda Petzold, PhD (Professor of Computer Science, University of California, Santa Barbara, CA)
  • Brian Drawert ,PhD (Assistant Professor, Computer Science, University of North Carolina, Asheville, NC)David Schoenfeld, PhD (Professor of
  • Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA)
  • Alexander Sherman, PhD (Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA)


Tyler Kinzy, MS