Pathophysiology & Two‑Hit Model

Dr. Feigenbaum and Dr. Baraki walk through the clinical workup of a 24 year old male presented with persistent weakness in his foot following weight loss of 22 pounds in two weeks. What could've possibly caused this?

The discussion pivots to the science of how fast one should lose weight. While athletes should prioritize slow loss to preserve performance and lean mass, the data for individuals with obesity suggests that the speed of loss may be less critical than protein intake and resistance training.

Timestamps:

• 00:00 - The Case of the Paralyzed Personal Trainer 
• 03:48 - How Doctors Build a Differential for Weakness 
• 12:08 - Interpreting Negative Labs and MRI Results 
• 15:04 - Identifying Foot Drop and Nerve Distribution 
• 20:53 - Understanding Nerve Conduction and EMG Studies 
• 26:06 - The Diagnosis: Slimmers Paralysis Explained 
• 32:56 - Are GLP-1 Medications Increasing Nerve Injury Risks? 
• 35:01 - Rapid vs Slow Weight Loss: Muscle Mass and Performance 
• 41:27 - The Truth About Metabolic Adaptation and Weight Regain
•  52:33 - New Research on Weight Regain After Stopping Medications 
• 58:32 - Clinical Recommendations for Sustainable Weight Management

 Key Learning Points (SPOILER ALERT)

• Slimmer’s Paralysis (Dieting Palsy): Discover how rapid fat loss depletes the protective structural fat pads at the fibular head, leaving the common peroneal nerve vulnerable to compression.
• The "Two-Hit" Model: Understand how the combination of biological depletion (rapid weight loss) and mechanical provocation (aggressive stretching or squatting) triggers focal weakness.
• Speed vs. Quality for Athletes: Evidence suggests that for trainees, a slower weight loss rate of $\sim$0.7% of body weight per week is superior for maintaining lean mass compared to faster rates.
• Metabolic Adaptation as a Signature of Success: Why a reduction in resting metabolic rate is an unavoidable adaptive response to weight loss and not necessarily a predictor of future weight regain.
• Diagnosing Focal Weakness: A step-by-step look at how clinicians differentiate between lumbar spine issues and peripheral nerve entrapment using physical exams and electrodiagnostic testing.

Resources:

Case: https://pubmed.ncbi.nlm.nih.gov/39809480/ 

• https://pubmed.ncbi.nlm.nih.gov/29503139/ 
• https://pmc.ncbi.nlm.nih.gov/articles/PMC12157737/ 
• https://pmc.ncbi.nlm.nih.gov/articles/PMC11273815/ 
• https://pubmed.ncbi.nlm.nih.gov/32576318/ 
• https://pubmed.ncbi.nlm.nih.gov/20443094/ 
• https://pubmed.ncbi.nlm.nih.gov/24372837/ 
• https://pubmed.ncbi.nlm.nih.gov/25459211/ 
• https://www.bmj.com/content/392/bmj-2025-085304 

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