Does Knee Replacement Surgery Trigger ALS?
No, knee replacement surgery does not trigger the onset of Amyotrophic Lateral Sclerosis (ALS), but surgery may temporarily accelerate disease progression in patients who already have undiagnosed ALS.
Key Evidence on Surgery and ALS
The relationship between surgery and ALS is limited to two specific scenarios, neither of which involves surgery causing the disease:
Surgery Does Not Cause ALS
- No established causal link exists between any surgical procedure, including knee replacement, and the development of ALS 1, 2.
- The only established risk factors for ALS are older age, male gender, and family history of ALS 2.
- ALS etiology remains largely unknown, with genetic factors (particularly C9orf72 gene mutations) accounting for 10-15% of cases, while 85-90% are sporadic with unclear causes 3.
Surgery May Correlate with ALS Onset Region (Not Causation)
- In patients who underwent surgery within 3 months before ALS symptom onset, there was a positive correlation between the surgical site and the region where ALS symptoms first appeared (p=0.032) 1.
- This correlation does not indicate causation—rather, it suggests that early ALS symptoms in a specific body region may have prompted surgical evaluation before the correct diagnosis was established 1.
Surgery May Accelerate Pre-existing Undiagnosed ALS
- Patients with slower-progressing ALS are at increased risk of undergoing surgery due to initial diagnostic difficulty and misdiagnosis 1.
- In patients who had surgery after ALS onset (often due to misdiagnosis), the rate of functional decline significantly accelerated during the 3-month period immediately following surgery (6.30%±8.10) compared to the 3 months before surgery (1.46%±1.35, p=0.005) 1.
- This acceleration was temporary, with progression rates returning closer to baseline in subsequent months (3.30%±3.10, p=0.006) 1.
Clinical Implications for Knee Replacement Patients
For Patients Without ALS Symptoms
- Proceed with knee replacement surgery as indicated based on standard orthopedic criteria 4.
- No special precautions regarding ALS risk are warranted, as surgery does not trigger the disease 1, 2.
For Patients With Unexplained Progressive Weakness
- Critical pitfall to avoid: In older patients presenting with knee problems and concurrent unexplained muscle weakness, fasciculations, or progressive functional decline, consider neurological evaluation before proceeding with elective surgery 1.
- Definite ALS diagnosis is important to avoid unnecessary surgical trauma and subsequent more rapid deterioration 1.
- The median time from symptom onset to ALS diagnosis is 14 months, during which patients may undergo inappropriate surgical interventions 2.
Understanding ALS Pathophysiology
ALS involves multiple pathogenic mechanisms that are entirely unrelated to surgical trauma:
- Protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, excitotoxicity, and inflammation all contribute to motor neuron degeneration 5.
- Autoimmune mechanisms with microglial cell activation at sites of neurodegeneration may play a role 2.
- Environmental factors have been proposed but remain unestablished as definitive risk factors 2, 6.