The study “Small fiber neuropathy: role in the diagnosis of diabetic sensorimotor polyneuropathy” (Malik et al., 2011) was published on behalf of the Toronto Consensus Panel on Diabetic Neuropathy.
The purpose of the study was to:
“address whether any definition of DSPN [Diabetic Sensory Polyneuropathy] should include a measure of SFN [Small Fibre Neuropathy]. Issues that arise before we can adopt the assessment of SFN to diagnose DSPN include establishing not only the reproducibility, sensitivity, specificity and accuracy but also the practical viability of any proposed test.
For the purposes of this review, we will consider the available evidence for established and emerging measures of ‘small fiber damage’ to diagnose and stratify the severity of DSPN.”
The study emphasises the need to focus on both small fibre dysfunction, as well as large fibre dysfunction, stating:
“Unfortunately, guidelines and consensus statements focus on large fibers and continue to advocate electrophysiology as a diagnostic modality and as a primary end point for the assessment of therapeutic benefit. (In part, this reflects the difficulties in quantifying small fiber dysfunction and damage.) We have therefore critically assessed currently available techniques that measure small fiber dysfunction in diabetic neuropathy, using quantitative sensory and sudomotor testing.”
Small fibres make up 70-90% of peripheral nerves and regulate key functions like tissue blood flow, temperature, pain perception and sweating. Studies show significant small fibre abnormalities in subjects with impaired glucose tolerance and diabetes, despite normal electrophysiology.
The study reviews a broad range of techniques for aiding in the diagnosis of small fibre neuropathy. The recommended suite of techniques includes sudomotor testing, such as that provided by Neuropad®. The techniques studied are as follows:
- Nerve biopsy, which has traditionally been used to quantify abnormalities in neurophysiology and may also predict development of future early DSPN. However, nerve biopsy is an invasive and highly specialized procedure which requires electron-microscopy with considerable expertise for quantification, and therefore cannot be advocated for routine use to diagnose early DSPN.
- Skin biopsy, which is less invasive than nerve biopsy. The American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation have concluded that skin biopsy may be considered for the diagnosis of DSPN.
- Quantitative sensory testing, evaluating thermal thresholds like warm and cold detection, has determined that although there is evidence that cold detection correlates with neuropathy in patients, there is little evidence that warm thresholds correlate. Nerve axon reflex/flare response has elicited some positive responses, but additional testing is recommended.
- The study states that sympathetic skin response (SSR) assesses sudomotor and hence small fibre dysfunction and has recently been shown to predict the risk of foot ulceration comparable with abnormalities in neuropathy disability score (NDS) and vibration perception. It has also been shown to have a sensitivity of 87.5% and a specificity of 88.2% for detecting diabetic autonomic neuropathy.
The study concludes that:
- Assessing both small and large fibres allows earlier DPN detection before symptoms and irreversible damage occur.
- Standardizing inclusion of small fibre assessment can improve DPN diagnosis, monitoring and therapeutic assessment.
Link to full study
Small fiber neuropathy: role in the diagnosis of diabetic sensorimotor polyneuropathy