Current challenges in primary lateral sclerosis diagnosis

ABSTRACT

Introduction

Primary lateral sclerosis (PLS) is a rare, adult-onset and slowly progressive motor neuron disorder whose clinical core is characterized by upper motor neuron (UMN) dysfunction. Its formal diagnosis is clinically based and disease duration-dependent. Differentiating PLS from other disorders involving UMN can be challenging, particularly in the early stages.

Areas covered

Our review covers and discusses different aspects of the PLS field, including the diagnostic criteria and its limitations, its differential diagnosis and their major pitfalls, and the actual role of neurophysiology, neuroimaging, genetics, and molecular biomarkers. Symptomatic treatment of the different manifestations is also addressed. The authors searched MEDLINE and Scopus. They also searched the reference lists of articles identified by our search strategy and reviewed and selected those deemed relevant. They selected papers and studies based on the quality of the report, significance of the findings, and on the author’s critical appraise and expertise.

Expert opinion

It is important to investigate novel molecular biomarkers and plan multicenter clinical trials for PLS. However, this will require a large international project to recruit enough patients, particularly given the diagnostic uncertainty of the current clinical criteria. A better understanding of PLS pathophysiology is crucial for designing disease-targeted therapies.

KEYWORDS:

• Amyotrophic lateral sclerosis
• differential diagnosis
• genetics
• electromyography
• primary lateral sclerosis

Article highlights

• PLS is characterized by a slowly progressive UMN dysfunction, usually starting with symmetrical involvement of lower limbs causing gait disturbance and falls.

• PLS is no longer considered as a ‘pure’ UMN syndrome, as other brain and spinal pathways are known to be involved.

• Distinguishing PLS from ALS is difficult, but new recent criteria have been proposed.

• Neurophysiological changes are essential to exclude signs of ALS; neurophysiology and imaging can be useful to confirm upper motor neuron involvement.

• Genetic abnormalities confirm that ALS and PLS are part of the same spectrum of diseases.

• Nowadays treatment is mainly supportive, but clinical trials will start in the future.

Acknowledgments

The authors are grateful to Ms Beatriz Carvalho for helping in preparing figures.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are supported by the Foundation for Science and Technology from the Ministry of Education and Science, Portugal via award AiPALS- PTDC/CCI-CIF/4613/2020.