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Instrumental Diagnosis
Electrodiagnostic tests include electromyography and electroneurography, and the study of reflex responses (eg, trigeminal reflexes) and can help to document peripheral nervous system abnormalities. Since peripheral causes of NP are the most common, these tests are important for many patients. Electrodiagnostic tests may identify the presence and extent of sensory damage in asymmetrical and symmetrical peripheral nervous system lesions, but their use in NP goes beyond the diagnosis in that they may offer information on the pathological process (myelin or axonal damage, neuropraxia or axonotmesis/neurotmesis, presence and degree of denervation), the site of the lesion (root, plexus, nerve trunk), the extent of damage (sensory or sensorimotor, involvement of other peripheral nervous sites, even subclinical) and the prognosis (timing and degree of reinnervation).
Somatosensory evoked potentials may document a lesion in the central sensory pathways in patients with suspected central NP, and give information on the pathological process (demyelination, degenerative), the site of the lesion (spinal cord, brain) and the presence of subclinical involvement at other sites.
Electrodiagnostic tests and somatosensory evoked potentials explore large myelinated nerve fibres and lemniscal pathways, which do not convey nociceptive afferents, but these tests are important in the diagnosis of NP because they are available in many neurological centres. They have diagnostic value, because most diseases causing NP do not result in damage or lesion limited to the nociceptive system, but extend to the whole peripheral nerve or involve non-nociceptive pathways.
In patients with selective damage to either small nerve fibres (eg, diabetic small fibre neuropathy) or central nociceptive pathways (eg, Wallenberg's syndrome), electrodiagnostic tests and somatosensory evoked potentials may be normal; instrumental tests, which selectively explore the nociceptive system, may be necessary to reach a definite diagnosis of NP. They include quantitative sensory testing, laser evoked potentials, skin biopsy, autonomic tests, microneurography and functional neuroimaging; these tests are usually available only in tertiary or specialised centres.
Quantitative sensory testing is non-invasive and measures a patient's response to thermal and mechanical stimuli of standardised intensity. It gives quantified information on detection and pain thresholds and may document abnormalities in nociceptive and non-nociceptive pathways. The limitations of quantitative sensory testing include the absence of a gold standard protocol, the need for patient's cooperation and the inability to demonstrate the anatomical level of damage to the nervous system. Quantitative sensory testing is of limited value in cases of malingering or when there is a suspected psychogenic component of pain.
Laser evoked potentials explore brain responses to laser stimuli, which cause a rapid increase in temperature in the epidermis and activate small nerve fibres. Laser evoked potentials may offer robust information on damage to small nerve (Aδ) fibres and nociceptive pathways, but they are invasive, expensive and cannot specify the anatomical level of somatosensory damage. Laser evoked potentials to C fibre stimulation and contact heat evoked potentials are less reliable and not routinely used.
Radiological tests, including conventional radiography, CT and MRI scans, are widely available and may confirm the lesion or disease, and so explain the NP. Nerve ultrasonography—performed only in specialised centres—may complement information obtained through electrodiagnostic testing.
The rationale of skin biopsy is that nociceptive (Aδ and C) nerve fibres free endings penetrate into the epidermis and may be seen with specific antibodies and quantified. The morphology and the density of intraepidermal nerve fibres correlate well with small nerve fibre dysfunction. Limitations of skin biopsy include its invasivity, cost, and the need strictly to follow standardised processing of specimen and nerve fibre counting.
Techniques to explore autonomic function include sympathetic skin response, measurement of sudomotor function and studying laser Doppler flow. These may help in patients with NP because nociceptive and autonomic systems share small peripheral nerve fibres. While such autonomic tests are less invasive and widely available their diagnostic role in NP needs further clarification.
Microneurography allows single fibre recording from peripheral nerve. This technique is time-consuming, invasive and needs detailed training of the examiner and cooperation from the patient. Microneurography has only a very limited or no clinical role and should be reserved for research purposes.
Functional neuroimaging includes positron-emission tomography and functional MRI techniques, which explore brain responses to spontaneous or evoked pain (ie, the pain matrix). Despite its role as a research tool, functional neuroimaging currently has no routine clinical use for NP.
There is a good correlation among quantitative sensory testing, laser evoked potentials and intraepidermal nerve fibre density; choosing the test to perform on an individual patient depends on the availability, specific clinical problem and personal preference.
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