Primary Lateral Sclerosis: Clinical, radiological and molecular features

Area of Science:

• Neurology
• Neuroscience
• Motor Neuron Diseases

Background:

• Primary Lateral Sclerosis (PLS) is an uncommon motor neuron disorder with challenging initial diagnosis and limited therapeutic options.
• Current awareness of recent research developments and dedicated clinical trials for disease-modifying therapies in PLS is limited.
• Traditionally viewed as a 'pure' upper motor neuron condition, emerging evidence highlights significant extra-motor clinical manifestations in PLS.

Purpose of the Study:

• To summarize recent advancements in Primary Lateral Sclerosis (PLS) research.
• To discuss the impact of new diagnostic criteria on the patient journey.
• To highlight emerging insights into the pathophysiology and clinical spectrum of PLS.

Main Methods:

• Review of recent scientific literature on Primary Lateral Sclerosis (PLS).
• Analysis of updated consensus diagnostic criteria for PLS.
• Examination of post-mortem studies, including TDP-43 reports.
• Inclusion of studies utilizing genetic profiling in PLS research.

Main Results:

• The introduction of 'probable' PLS in diagnostic criteria is expected to shorten the diagnostic timeline for patients.
• Recognition of extra-motor symptoms challenges the historical definition of PLS.
• TDP-43 reports and genetic profiling are expanding the post-mortem and molecular understanding of PLS.
• Recent research has significantly accelerated the generation of novel academic insights into PLS.

Conclusions:

• Research in Primary Lateral Sclerosis (PLS) is rapidly advancing, providing new academic insights.
• These developments hold potential for significant clinical ramifications and improved patient management.
• The evolving understanding of PLS encompasses broader clinical manifestations and genetic underpinnings.