Small Fibre Neuropathy
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
The majority of peripheral sensory nerves are unmyelinated C fibres and thinly myelinated Aδ fibres.
- 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 |
Aetiopathology
Disorders known to contribute to SFN are listed below.[1] SFN is a generalised sensory nerve disease process with abnormalities in the structure and function of affected nerve fibres. It is histopathologically characterized by degeneration of small nerve fibre endings. The small unmyelinated nerves are affected.
- 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
The majority of peripheral sensory nerves are unmyelinated C fibres and thinly myelinated Aδ fibres. There is no clear way of diagnosing pathology in these fibres.
Classical 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.
Patients with SFN may have severe symptoms but a normal physical and neurological examination. Proprioception, light touch, and vibration sense may also be normal. Some patients may have decreased pinprick, decreased thermal sensation, hyperalgesia in the affected region, and slightly decreased vibratory sense.
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).
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
Standard electrophysiologic testing is typically normal in SFN as the pathology lies in the small unmyelinated nerve fibres. Sural nerve biopsy may be only minimally abnormal, or even normal.[1]
Quantitative sensory testing (QST) is an extension of the physical examination, and can be used to diagnose peripheral nervous system disorders. In QST the clinician determines the sensation and pain thresholds for cold and warm, vibration sense, and compares results to normative values. There are some important limitations. Either central or peripheral nervous system abnormalities can cause the same deficit. QST requires good cognitive function and good conscious patient reactions.[1]
The Quantitative Sudomotor Axon Reflex Test (QSART) is used to evaluate autonomic function, in particular the peripheral sympathetic cholinergic nervous system. It measures the response of the autonomic sudomotor nerves. Iontophoresis is used to introduce acetylcholine into the skin, which stimulates the sweat glands. The volume of sweat produced is measured. Some patients with SFN have increased sweat production. [1]
Skin Biopsy
Skin biopsy is the best diagnostic tool and current gold standard. 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,
