Small Fibre Neuropathy
The Small fibre neuropathy (SFN) and large fibre neuropathy belong to a group of diseases known as peripheral neuropathies. Polyneuropathy refers to cases where either the large fibres are affected, or both the large and small fibres are affected. SFN refers to isolated small fibre involvement. About 40-50% of patient with fibromyalgia meet the diagnostic criteria for SFN.[1]
Nerve Anatomy
- Characteristics of sensory nerve fibres
| Nerve fibre | Myelinated axons | Diameter (µm) | Conduction velocity (m/s) | Sensory information | Usefulness of electroneuromyography | Usefulness of QST |
|---|---|---|---|---|---|---|
| Aα | Yes | 13-20 | 80-120 | Proprioception, muscle spindle primary endings (Ia), golgi tendon organs (Ib) (and alpha motor neurons) | Yes (H reflex) | No |
| Aβ | Yes | 6-12 | 33-75 | Discriminative mechanoreception (touch, vibration), proprioception, pain modulation (block nociceptive information, allodynia in sensitisation) | Yes (sensory nerve conduction) | Yes |
| Aγ | Yes | 4-8 | 15-40 | Touch, pressure (and gamma motor neurons) | No | |
| Aδ | Thin | 1-5 | 3-30 | "rapid" pain, crude touch, pressure, temperature. AMH type I for rapid mechanical pain (high heat threshold >53C), AMH type II for rapid heat pain (lower heat threshold 43-47C). | No | Yes |
| C | No | 0.3-1.5 | 0.5-2.0 | "slow" pain, touch, pressure temperature (and postganglionic autonomic). Polymodal. | No | Yes |
Aetiology
Disorders known to contribute to SFN are listed below.[1]
- Metabolic
- Diabetes mellitus
- Glucose intolerance
- Vitamin B12 deficiency
- Hypothyroidism
- Hiperlipidemia
- Hipervitaminosis B6
- Chronic kidney disease
- Dysimmunity/inflammatory diseases
- Sjögren’s syndrome
- Sarcoidosis
- Systemic lupus erythematosus
- Celiac disease
- Infectious
- HIV
- Hepatitis C
- Ebstein-Barr virus
- Lyme disease
- Leprosy
- Toxic agents and medications
- Alcohol (this can eventually cause large fibre neuropathy)
- Antibiotics (metronidazole, nitrofurantoin, linezolid, isoniazid)
- Anticancer agents (bortezomib, platin)
- Antiretroviral drugs
- Genetic diseases
- Fabry’s disease
- Familial amyloid polyneuropathy (transthyretin)
Clinical Features
Small fibre sensory neuropathy can cause severe symptoms but there can be minimal objective findings on examination. Class symptoms include distal burnings, pain, numbness, paraesthesia, and autonomic symptoms. Autonomic symptoms can include sweating alterations, temperature dysregulation, dry mouth and eyes, and erectile dysfunction. Most affected patients have a combination of positive signs (e.g. hyperalgesia, and allodynia), and negative signs (e.g. diminished pin prick and temperature sense). Standard electrophysiologic testing is typically normal with disorders that affect mainly the small, unmyelinated nerve fibres. Sural nerve biopsy may be only minimally abnormal, or even normal.
40-50% of patients with fibromyalgia meet the diagnostic criteria for SFN. In one small study, fibromyalgia patients with SFN were more likely to report dysautonomia and paraesthesias.[1]
Diagnosis
Skin Biopsy
Skin biopsy is the best diagnostic tool. It is performed using a 3mm punch under sterile technique. It can be taken from any body part, but the standard biopsy is 10cm above the lateral malleolus to enable evaluation of the loss of the most distal sensory endings that are typical of length dependent axonal neuropathy. Another site is the upper thigh (20cm distal to the iliac spine). The guidelines on performing the skin biopsy were established by the European Federation of Neurological Societies in 2005. The biopsy should be 2mm thick to enable assessment of both the epidermis and dermis. Suturing is not required. Risks include infection, tenderness at biopsy site, delayed healing, bleeding, allergy.[1]
The biopsy sample is stained immunohistochemically with antibodies against protein gene product 9.5 (PGP 9.5). This protein is a marker for peripheral nerve fibres and neuroendocrine cells. Most cutaneous nerve fibres are unmyelinated, but in the dermis of hair skin 10% are small diameter myelinated fibres (A-delta fibres). A fibre count is done, and single axons are counted that cross or originate at the epidermal-dermal junction. The result is the Epidermal Nerve Fibre Density (ENFD). Reduced ENFD has a 90% specificity and 82.6% sensitivity for small fibre neuropathy.[1]
Management
There is no known cure for SFN. Standard neuropathic pain medications can be trialled such as gabapentinoids, topiramate, TCAs, and SNRIs. The combination of a TCA and gabapentinoid may be more effect than monotherapy.[1] Opioids are not recommended, but weak opioids such as codeine or tramadol can be considered for short periods of use only. Topical lidocaine or capsaicin has been used.
See Also
References
Literature Review
Literature Review
- Reviews from the last 7 years: review articles, free review articles, systematic reviews, meta-analyses, NCBI Bookshelf
- Articles from all years: PubMed search, Google Scholar search.
- TRIP Database: clinical publications about evidence-based medicine.
- Other Wikis: Radiopaedia, Wikipedia Search, Wikipedia I Feel Lucky, Orthobullets,
