PLS Natural History Study


About this study

The purpose of this study is to develop a natural history dataset and biorepository of early Primary Lateral Sclerosis (PLS) and well-established PLS cases for future clinical trials.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Adult participants (≥ 25 years of age).
  • PLS diagnosis is based on the new PLS diagnostic criteria.
  • Symptom onset was no more than 15 years prior to baseline.
  • Ability to independently walk with or without an assistive device (e.g., walker) at the baseline evaluation.
  • In cases where a molecular test has been done prior to enrollment in this study, HSP or HSP- related mutations are negative.
  • Expected to have at least some bulbar symptoms (dysarthria, dysphagia, drooling or pseudobulbar affect); however, the absence of these symptoms will not exclude participants when molecular testing is negative for known HSP.
  • UMN symptoms and signs in a region other than the legs.
  • Normal brain and spinal cord neuroimaging except for changes expected for PLS.
  • No active major neurological diseases other than PLS and no history of major neurological diseases.
  • No major unstable medical diseases that require treatment (e.g., active cancer, dialysis) in the past 6 months.
  • Participant is residing within a commutable distance to the study site and is willing to visit the study site as required.
  • No history of ALS or PLS in immediate family and no family history of hereditary spastic paraplegia (HSP).
  • gia (HSP) If disease duration is less than 5 years, no significant lower motor neuron (LMN) degeneration upon the EMG examination within 12 months before enrollment (evident entrapment neuropathy or radiculopathy are acceptable). If EMG tests were not done in this period, an EMG test should be obtained through regular patient care (through insurance) in order to make a diagnosis of PLS (this cost will not be covered by this research study). If disease duration is more than 5 years and at least one EMG was performed post-diagnosis, an EMG examination 12 months prior to enrollment is not required.
  • Participant understands the study’s purpose, has capacity to consent, and is willing to sign the informed consent form.

Exclusion Criteria:

  • Unwilling or unable to give informed consent.
  • UMN symptoms and signs only in the legs.
  • Unwilling or unable to visit the study site as required.
  • Clinically obvious cognitive impairment that precludes obtaining informed consent, as determined by the site PI.
  • Participating in clinical treatment trials.

Eligibility last updated 5/3/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Eric Sorenson, M.D.

Open for enrollment

Contact information:

Megan Means M.B.A.

(507) 293-0545

Jacksonville, Fla.

Mayo Clinic principal investigator

Jaimin Shah, M.D.

Open for enrollment

Contact information:

ALS Research Team

(904) 953-6912

More information


Publications are currently not available

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