What is Small Fiber Neuropathy?
Small fiber neuropathy (SFN) is a disorder affecting the small nerve fibers of the peripheral nervous system—specifically the thinly myelinated Aδ fibers and unmyelinated C fibers—which constitute 79.6% to 91.4% of all peripheral nerve fibers and are responsible for pain, temperature perception, and autonomic functions. 1, 2
Key Pathophysiological Features
- These small fibers cannot be detected by conventional nerve conduction studies, which only assess large myelinated fiber function, making SFN diagnostically challenging 2, 3
- Small fiber damage often precedes large fiber damage, particularly in diabetic neuropathy, meaning patients can have significant neuropathy despite normal electrophysiology 2, 3
- The Aδ fibers are finely myelinated while C fibers are unmyelinated, both critical for nociception and thermoregulation 4
Clinical Symptoms of Small Fiber Neuropathy
Sensory Symptoms (Most Prominent)
The hallmark presentation is distal, symmetric, neuropathic pain that worsens at night, typically starting in the feet and ascending proximally 1, 2
Patients describe their pain using specific descriptors:
- Burning pain (most common) 4, 5
- Prickling or tingling sensations 1
- Aching pain 1
- Sharp, stabbing, electric shock-like pains (intermittent) 1
On examination, clinicians can elicit:
- Dysesthesias (unpleasant abnormal sensations) 1
- Allodynia (pain from normally non-painful stimuli) 1
- Pinprick hypoesthesia (reduced sharp sensation) in approximately 50% of patients 5
- Thermal hypoesthesia (reduced temperature sensation) in approximately 50% of patients 5
Pain intensity in SFN is typically more severe than in large fiber or mixed fiber neuropathies 5
Autonomic Symptoms (Very Common)
Approximately 70% of SFN patients exhibit signs of peripheral vascular autonomic dysfunction 5
Specific autonomic manifestations include:
- Postural hypotension 2
- Bladder disturbances 2
- Reduced heart rate variability 2
- Sudomotor dysfunction (abnormal sweating), which contributes to plantar ulceration in diabetic patients 2, 3
Clinical Patterns and Distribution
- Length-dependent polyneuropathy is the typical presentation, though other distributions can occur 6
- Symptoms usually begin in the feet and hands, progressing proximally in a "stocking-glove" distribution 4
- Nocturnal exacerbation is characteristic 1, 2
Important Clinical Caveats
A critical pitfall is relying solely on nerve conduction studies, which will miss SFN entirely since these tests only evaluate large fiber function 2, 3. This leads to underdiagnosis in clinical practice.
Patients should be cautioned against excessive cooling of extremities as a pain relief strategy, as this may worsen tissue damage and lead to ulcerations 2, 3
The clinical picture can remain stable in 45.6% of patients over 2 years, but 13% may progress to involve large nerve fibers, 30.4% experience worsening pain, and only 10.9% achieve spontaneous remission 5