When a patient presents with sensory changes, pain, and/or weakness in the upper extremity, the first task is to localise the level of the lesion in the nervous system, as this narrows down the list of possible[Figure caption and citation for the preceding image starts]: Approximate distribution of ulnar sensory nerve on palmFrom the collection of Hannah R. Briemberg, MD, FRCPC [Citation ends].com.bmj.content.model.assessment.Caption@685fdc52[Figure caption and citation for the preceding image starts]: Approximate distribution of ulnar sensory nerve on dorsum of handFrom the collection of Hannah R. Briemberg, MD, FRCPC [Citation ends].com.bmj.content.model.assessment.Caption@5a65bbef[Figure caption and citation for the preceding image starts]: Approximate distribution of radial sensory nerveFrom the collection of Hannah R. Briemberg, MD, FRCPC [Citation ends].com.bmj.content.model.assessment.Caption@741db299[Figure caption and citation for the preceding image starts]: Approximate distribution of median sensory nerve on palmFrom the collection of Hannah R. Briemberg, MD, FRCPC [Citation ends].

Localisation of lesions

Localisation usually requires a careful history and physical examination followed by electromyography (EMG) to confirm or refute clinical suspicions. EMG is potentially useful not only in localising the level of the lesion but also in helping to determine whether the lesion is acute or chronic and whether the aetiology is axonal or demyelinating. This is important, as demyelinating lesions tend to have a better chance of complete recovery than do axonal lesions. Also, a different underlying aetiology is implied in demyelinating lesions (e.g., multifocal chronic inflammatory demyelinating polyneuropathy) compared with axonal (e.g., peripheral nerve vasculitis).

Once the location of nerve pathology is determined, there is usually only a limited set of possible aetiologies that direct further work-up and/or[Figure caption and citation for the preceding image starts]: Testing thumb abduction strength in assessment of carpal tunnel syndrome: with palm facing up, patient lifts thumb towards ceiling, and resistance is applied as shownFrom the collection of Hannah R. Briemberg, MD, FRCPC [Citation ends].

Initial tests

Electrodiagnostic testing (nerve conduction studies and EMG)[16]

  • Can confirm the diagnosis of mononeuropathy

  • Localises the site of the entrapment or other pathology

  • Helps to assess timing of nerve damage (acute, subacute, chronic)

  • Provides prognostic value in combination with history and clinical examination; more severe axonal loss, neurotmesis, longer duration of symptoms, older patient age, increased patient height, and more proximal lesions are poor prognostic indicators.

  • Can evaluate more widespread nerve disease.

Laboratory evaluation

  • Erythrocyte sedimentation rate, C-reactive protein, and complement levels can be checked in patients with signs and symptoms suggestive of peripheral nerve vasculitis.

Imaging studies

  • MRI or CT is indicated when there is concern about central nervous system disorders (e.g., cervical myelopathy, multiple sclerosis, stroke), spinal nerve root impingement, or brachial plexus lesion. Generally, MRI is more sensitive than CT for these types of lesions.

Rarely patients have ulnar neuropathy at the wrist or palm caused by a ganglion cyst or other structural mass lesion. If EMG localises the lesion to the distal branches of the ulnar nerve, or if palpation suggests the presence of a ganglion cyst, this can be further evaluated by ultrasound or MRI of the wrist and/or palm.

MRI and/or ultrasound are appropriate investigations for brachial plexus pathology and/or ganglion cysts. Although electrodiagnostic testing remains the gold standard for diagnosis of compression neuropathies, studies have demonstrated that median nerve ultrasound has good sensitivity and specificity in the diagnosis of carpal tunnel syndrome.[17][18][19][20]

Further specific tests

Other tests are used for more specific diagnoses, depending on the results of nerve conduction studies and EMG in the context of the history and examination:

  • FBC with differential for haematocrit in peripheral nerve vasculitis

  • Antinuclear antibody and anti-DNA antibodies for peripheral nerve vasculitis

  • Antineutrophil cytoplasmic antibody and rheumatoid factor for peripheral nerve vasculitis

  • Cryoglobulins for peripheral nerve vasculitis

  • Hepatitis B and C antibodies for peripheral nerve vasculitis

  • Nerve and muscle biopsy for peripheral nerve vasculitis or sarcoidosis

  • Cervical spine x-ray for cervical rib for neurogenic thoracic outlet syndrome

  • Biopsy of skin lesions or affected nerve for leprosy

  • HIV/CD4 testing

  • Polymerase chain reaction cytomegalovirus testing

  • Lyme serology

  • Serum and urine protein electrophoresis for amyloidosis

  • Tissue biopsy of abdominal fat pad, rectal mucosa, or affected nerve for amyloidosis

  • Lumbar puncture for multifocal chronic inflammatory demyelinating polyneuropathy

  • Genetic testing for hereditary neuropathy with liability to pressure palsies.

Evidence-based work-up

Very few studies exist to guide the practitioner through work-up of these symptoms in a systematic and evidence-based manner. Most published recommendations result from expert consensus rather than from the results of published studies. If, based on the history and examination findings, there is a high risk of malignancy, infection, or vasculitis, initial work-up should entail urgent imaging studies (malignancy) or appropriate blood tests (infection, vasculitis). Based on the imaging and/or blood test results, biopsy may then be indicated before starting treatment. If these conditions are unlikely, often little work-up is necessary, other than EMG to confirm the clinical suspicion of a compressive mononeuropathy.

Musculoskeletal pathologies

Osteoarthritis, tendinitis, or repetitive strain symptoms are often confused with carpal tunnel syndrome and/or ulnar neuropathy, as the distribution of pain can be similar in these entities. Electrophysiological studies can help identify or exclude an associated mononeuropathy in these cases.

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