Brachial Neuritis

Brachial neuritis (BN) exists in an inherited and an idiopathic form. In the idiopathic version, the pathophysiology is unknown, but the condition is generally thought to be an immune system–mediated inflammatory reaction against nerve fibers of the brachial plexus.[11, 12, 13, 14, 15] Axonopathy with subsequent Wallerian degeneration appears to predominate, but proximal conduction block has also been described in over 33% of cases in the series by Lo and Mills.[16] The inherited form is autosomal dominant and has been linked to mutations in the SEPT9 gene on chromosome 17q.[17, 18, 19] Septins are involved in the formation of the cytoskeleton and in cell division, but how these mutations result in BN is unknown.

A study by Arányi et al described the ultrasonographic characteristics of brachial neuritis, finding the following abnormalities in a group of 14 patients:

• Focal or diffuse nerve or fascicle enlargement

• Incomplete nerve constriction

• Complete nerve constriction with torsion

• Fascicular entwinement

The investigators suggested that inflammation-related constriction precedes torsion, with the torsion encouraged by limb rotation.[20]

Using magnetic resonance imaging (MRI) to evaluate patients with brachial neuritis, a study by Sneag et al suggested that instead of being associated with changes to all or part of the brachial plexus proper, the condition involves one or more mononeuropathies.[21]

A study by Ferrante and Wilbourn of 281 patients with sporadic brachial neuritis found through electrodiagnostic testing that out of 379 assessable events, 174 (46%) involved a single nerve, with another 205 (54%) being multifocal. The investigators also found that most bouts of brachial neuritis purely involved motor nerves, with the second greatest number involving mostly motor nerves and the fewest involving a more even mix of sensory and motor nerves.[22]

A study by Lustenhouwer et al indicated that in patients with brachial neuritis, alterations occur in the cerebral sensorimotor representations of the affected upper limb. The results were derived from a hand laterality judgement task, in which individuals with brachial neuritis demonstrated less accuracy in laterality judgements of their affected limb than did controls. The report suggested that in brachial neuritis, “maladaptive central neuroplasticity may occur in response to peripheral nerve damage, thereby contributing to motor dysfunction” and that treatments aimed at changing cerebral sensorimotor representations may be effective against the condition.[23]

Frequency

United States

The incidence of brachial neuritis is approximately 1-2 cases per 100,000 person-years.

International

In the United Kingdom, the incidence of brachial neuritis is approximately 3 per 100,000 person-years.[24] Brachial neuritis has also been described in many countries around the world, although specific rates of incidence have not been reported.

A prospective cohort study from the Netherlands suggested that the incidence of brachial neuritis is many times higher than currently thought. Using data from two primary care institutions, the study, by van Alfen and colleagues, found that out of 492 patients with new-onset neck, shoulder, or arm complaints, 14 were confirmed to have brachial neuropathy, putting the 1-year incidence rate for the condition at 1 per 1000 persons. According to the investigators, this indicated an incidence for the condition that is 30-50 times greater than currently believed.[25]

Mortality/Morbidity

Brachial neuritis is not a fatal condition, although the phrenic nerve may be involved.[26] The risk of 'significant' residual disability in the involved limb after 2 years is approximately 10-20%.[27] . A recent survey suggested that up to half of patients are left with residual shoulder pain and decreased endurance.[28]

Sex

Brachial neuritis occurs predominantly in males, with the male-to-female ratio for the condition ranging from 2:1 to 4:1.

Age

Brachial neuritis has been reported in individuals from age 3 months to 74 years; however, the condition's prevalence is highest in young to middle-aged adults. Onset in childhood should be considered suggestive of hereditary brachial neuritis.[29]

See the list below:

• The onset of pain in brachial neuritis (BN) is often abrupt and may follow recent illness, surgery,[8] immunization, or even trauma (see Causes, below). Up to two thirds of cases begin during the nighttime.

• The pain usually is localized to the right shoulder region, but it may be bilateral in 10-30% of cases.

• The pain's intensity is very high (9+/10) and is maximal at onset.

• Usually, the pain is described as sharp or throbbing in nature.

• The pain usually is constant, but it is exacerbated by movements of the shoulder. Movements of the neck, coughing, and/or sneezing usually do not worsen the pain.

• Intense pain can last from a few hours to several weeks and requires opiate analgesia.

• Low-grade pain may persist for up to a year.

• As the pain subsides, weakness becomes apparent.

  • In most cases of BN, this weakness manifests within about 2 weeks of onset.

  • Weakness is maximal at onset but can progress over 1 or more weeks.

  • A wide variety of muscles is affected, particularly those innervated by the upper trunk. The supraspinatus, infraspinatus, serratus anterior, and deltoid muscles are particularly susceptible, but many different single and multiple combinations of muscle involvement, including a pure distal form, have been reported.

  • The patient may notice considerable atrophy and wasting, as well as a deep aching in the affected muscles.

• Numbness may occur, depending on the particular nerves affected, and usually is found in the nerve distribution corresponding to maximal muscle weakness. However, numbness is rarely a prominent complaint.

• Phrenic nerve involvement occurs in up to 5% of cases and can result in significant shortness of breath.[30, 31, 32]

• Variants of BN can present with isolated or multiple cranial neuropathies (IX, X, XI, XII).[33]

• In 25-50% of patients, the medical history indicates a viral illness or vaccination that occurred days or weeks prior to the onset of symptoms. Some patients also may note recent trauma or severe exercise, surgery, infection, or immunization.

See the list below:

• Due to the extreme pain involved, patients with brachial neuritis usually present acutely. Typically, the affected arm is supported by the uninvolved arm and is held in adduction and internal rotation.

• Atrophy of the affected muscles becomes prominent after approximately 2 weeks.

• Considerable muscle pain may be noted on palpation.

• Passive and active attempts at shoulder and scapular movement result in a significant increase in pain. Movements of the neck are relatively pain free.

• Muscle strength in affected muscles often is reduced severely (to 2 or less on the Medical Research Council [MRC] grading scale).

• Reflexes may be reduced or absent, depending on which nerves are involved.

• Sensory loss is not prominent but may be detectable (in particular, loss of axillary nerve sensation), depending on the specific nerves affected.

The exact cause of brachial neuritis is unknown, but the condition is thought to be associated with an immune-mediated response to an as yet poorly understood trigger. Brachial neuritis has been linked to many antecedent events or illnesses, as follows:

• Viral infection (particularly of the upper respiratory tract)

• Bacterial infection (eg, pneumonia, diphtheria, typhoid)

• Parasitic infestation

• Surgery[8]

• Trauma (not related to shoulder)

• Vaccinations (eg, influenza, tetanus, diphtheria, tetanus toxoids, pertussis [DPT], smallpox, swine flu)

• Childbirth

• Miscellaneous medical investigative procedures (eg, lumbar puncture, administration of radiologic dye)

• Systemic illness (eg, polyarteritis nodosa, lymphoma, systemic lupus erythematosus, temporal arteritis, Ehlers-Danlos syndrome)

A rarer, hereditary form of BN has been localized to the SEPT9 gene on chromosome arm 17q and should be considered a distinct disorder. This entity presents in a younger age group, affects males and females equally (autosomal-dominant inheritance), and is characterized by recurrent, often bilateral attacks. Dysmorphic facial features (eg, hypotelorism, long nasal bridge, facial asymmetry) can also be present.

A study from England and the Netherlands found that in samples of British and Dutch patients with brachial neuritis, about 10% had hepatitis E. In the combined retrospective (British)/prospective (Dutch) study, van Eijk et al found hepatitis E virus (HEV) infection in five out of 47 patients. Clinical and electrophysiologic examination indicated that the brachial neuritis was bilateral in all of the patients with hepatitis E.[34, 35]

A study by Ripellino et al found that of 141 cases of acute HEV infection in southern Switzerland, 43 patients (30.5%) had neurologic symptoms, with 28 patients (19.9%) having myalgia, and 15 patients (10.6%) having brachial neuritis.[36]

The French National Agency for the Safety of Medicines and Health Products (ANSM) reported evidence of brachial neuritis as an adverse effect of mRNA vaccinations for coronavirus disease 2019 (COVID-19). For example, serious brachial neuritis cases were found in six individuals who received the Pfizer/BioNTech vaccine, with symptoms developing within 50 days post-vaccination; three cases occurred after the first vaccine dose, and three were reported after the second. The patients were aged 19 to 69 years. Two cases developed less than 18 days post-vaccination in patients who received the Moderna vaccine, with brachial neuritis arising after the first dose in one patient and after the second dose in the other. A third case associated with the Moderna product occurred a number of weeks following vaccination. There is also some evidence of brachial neuritis arising in a small group in association with AstraZeneca’s viral vector vaccine.[37]

Laboratory values are usually within the reference range. Laboratory studies are indicated only if systemic disease is suspected on clinical grounds. The complete blood count (CBC) and erythrocyte sedimentation rate (ESR) can be used as nonspecific indicators of systemic disease. Antinuclear antibody (ANA) values can be used as a marker for connective-tissue disease. Human immunodeficiency virus (HIV) serology can also be performed.

Magnetic resonance imaging (MRI) or computed tomography (CT) myelogram scanning should be considered initially to rule out cervical radiculopathy (particularly C5/C6). MRI of the brachial plexus can help to rule out carcinomatous or granulomatous infiltration, if clinically indicated.[9, 10] Some of the newer MRI techniques, especially high-resolution MR neurography, can show abnormalities in the proximal root/plexus that may not be apparent with other investigations.[38]

A study by Sneag et al indicated that in patients with brachial neuritis, hourglass nerve constriction can be localized through identification of a bull’s-eye sign on MRI scans.[39]

A study by Lieba-Samal et al indicated that MRI and high-resolution ultrasonography (HRUS) can be useful in diagnosing brachial neuritis, with all clinically affected nerves/trunks of the study’s six brachial neuritis patients revealing segmental swelling on HRUS. In the five patients who underwent MRI, all clinically affected nerves displayed T2-weighted hyperintensity.[40]

A shoulder radiograph may be indicated to rule out specific shoulder pathologies. A chest radiograph is not usually part of the initial workup; however, it can be useful to rule out sarcoidosis or other granulomatous disease, as well as Pancoast tumor.

See the list below:

• Electrodiagnosis[12, 41, 42, 7, 43]

  • Electrodiagnosis should be considered initially to confirm neuropathic diagnosis and to rule out various other conditions (eg, radiculopathy, neuropathy, amyotrophic lateral sclerosis).

  • Specific localization can be made to various nerves.

  • Loss of sensory and motor amplitudes with relatively normal conduction velocity is frequent. Note, however, that this finding only begins to fall beyond the reference range after approximately 1 week.

  • Somatosensory evoked responses are not reliable for distinguishing radiculopathy from brachial plexus neuropathy, and F-waves are generally less helpful than routine conduction studies in localization.

  • Needle electromyogram (EMG) shows denervation (fibrillations, positive sharp waves, and/or motor unit potential changes) in affected muscles 2-3 weeks after onset; however, clinically uninvolved muscles also may show abnormalities. Approximately 50% of patients with unilateral clinical involvement demonstrate bilateral EMG abnormalities. EMG results for the paraspinal muscles usually are within the reference range. Electromyographic exclusion of a radiculopathy may be challenging. In addition, strict anatomic localization often is difficult.

  • Proximal conduction block has been reported in brachial neuritis; however, this finding should suggest focal forms of inflammatory demyelinating diseases. Proximal slowing also may occur from loss of large fibers, regenerating fibers, and/or segmental demyelination.

See the list below:

• Nerve biopsy usually is not indicated in brachial neuritis. Axonal loss rarely is identified with biopsies of the radial sensory branch.

• Lumbar puncture usually is not indicated. Analysis of cerebrospinal fluid generally is within the reference range in individuals with brachial neuritis.

Physical Therapy

Physical therapy for patients with brachial neuritis should be focused on the maintenance of full range of motion (ROM) in the shoulder and other affected joints.[7] Passive ROM (PROM) and active ROM (AROM) exercises should begin as soon as the patient's pain has been adequately controlled; these should be followed by regional conditioning of the affected areas. Strengthening of the rotator cuff muscles and scapular stabilization may be indicated. Passive modalities (eg, heat, cold, transcutaneous electrical nerve stimulation [TENS]) may be useful as adjunct pain relievers.

Occupational Therapy

Functional conditioning of the upper extremity may be helpful in patients with brachial neuritis. Assistive devices and orthotics may be used, depending on the particular disabilities present. The occupational therapist may be involved in maintaining ROM and strengthening, particularly if the hand and wrist are involved.

Treatment is largely symptomatic in patients with brachial neuritis (BN), and opiate analgesia often is necessary in the initial period. Immunosuppressive therapy (eg, steroids, immunoglobulin, plasma exchange) is not known to be beneficial for the condition.[44, 45]

However, a study by van Eijk et al indicates that oral prednisolone, a corticosteroid, may be an effective pain treatment for BN.[46] The investigators compared pain relief and strength recovery in 2 groups of patients with BN, one of which (50 patients) received prednisolone during the acute phase of the condition, and the second of which (203 patients) did not receive the drug.

The authors found that the median time required for initial pain relief was 12.5 days in the first group, compared with 20.5 days in the untreated patients. Moreover, 18% of the prednisolone patients recovered strength within the first month of treatment, while only 6.3% of the control group did. In addition, 12% of patients in the prednisolone group attained a full recovery within 1 year, while only 1% of the untreated group fully recovered within that period. The authors recommended that oral prednisolone be used during the acute phase of BN, but they also advised that a prospective, randomized trial be conducted to verify their results.

In brachial neuritis, nerve grafting or tendon transfers may be considered for the few patients who do not achieve good recovery by 2 years. Surgery usually is aimed at improving shoulder abduction.

See the list below:

• A specialist in neuromuscular disease may be consulted to confirm a diagnosis of brachial neuritis and to evaluate any potentially underlying causes.

• A specialist in neuromuscular rehabilitation may be asked to provide a comprehensive rehabilitation program for the patient, aimed at maintaining ROM and improving strength and function.

The goal of pharmacotherapy is to reduce morbidity, provide therapeutic analgesia, and prevent complications.

Class Summary

Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties beneficial to patients who have sustained trauma or who experience pain. These agents are necessary for initial pain control.[7]

Acetaminophen (Tylenol, Panadol, Aspirin Free Anacin)

DOC for pain in patients with documented hypersensitivity to aspirin or NSAIDs, who have been diagnosed with upper GI disease, or who are on oral anticoagulants.

Acetaminophen and codeine (Tylenol #3)

Indicated for the treatment of mild to moderate pain.

Hydrocodone bitartrate and acetaminophen (Vicodin ES)

Drug combination indicated for moderate to severe pain.

Oxycodone and acetaminophen (Percocet)

Drug combination indicated for the relief of moderate to severe pain. DOC for aspirin hypersensitive patients.

Class Summary

Tricyclic antidepressants (TCAs) are a complex group of drugs that have central and peripheral anticholinergic effects and sedative effects. They block the active reuptake of norepinephrine and serotonin.

Nortriptyline (Pamelor)

Low-dose tricyclic antidepressant (TCA) medication for neuropathic pain management. Nortriptyline has demonstrated effectiveness in the treatment of chronic pain. It increases the synaptic concentration of serotonin and norepinephrine in the central nervous system (CNS) by inhibiting their reuptake by the presynaptic neuronal membrane. Additional pharmacodynamic effects, such as desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors, appear to play roles. (Off-label use for this diagnosis)

Doxepin (Silenor)

Low-dose tricyclic antidepressant (TCA) medication for neuropathic pain management. Doxepin increases the concentration of serotonin and norepinephrine in the CNS by inhibiting their reuptake by presynaptic neuronal membrane. It inhibits histamine and acetylcholine activity and has proven useful in treatment of various forms of depression associated with chronic pain. (Off-label use for this diagnosis)

Class Summary

GABA analogs are used to alleviate painful dysesthesias, which frequently accompany peripheral neuropathies. Although they have many different mechanisms of action, their use for alleviating neuropathic pain probably depends on their general tendency to reduce neuronal excitability.

Gabapentin (Neurontin, Gralise, Neuraptine, Fanatrex FusePaq)

Gabapentin has properties common to other anticonvulsants and exerts antineuralgic effects. Its exact mechanism of action is not known. Gabapentin is structurally related to gamma-aminobutyric acid (GABA) but does not interact with GABA receptors. It has efficacy at the alpha2-delta subunit. (Off-label use for this condition)

Pregabalin (Lyrica, Lyrica CR)

Pregabalin is a structural derivative of GABA. Its mechanism of action is unknown; it is known to bind with high affinity to alpha2-delta subunits of calcium channels. In vitro, pregabalin reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium-channel function. (Off-label use for this condition)

The treatment of brachial neuritis (BN) usually is completed conservatively on an outpatient basis. Surgical intervention is indicated for patients who do not demonstrate good recovery after 2 years of conservative care. Please refer to the Rehabilitation Program section for a discussion of outpatient rehabilitation and treatment options for individuals with BN.

Shoulder joint contractures (and potentially others) can occur. Sudden, severe dyspnea due to phrenic nerve involvement may be noted with or without other symptoms of brachial neuritis;[26] however, there should be no other evidence of lung disease.

Eighty percent of patients with brachial neuritis recover functionally within 2 years; 90% recover functionally within 3 years.[12]  A study by Feinberg et al found that at a mean period of 1 year, 31% of affected nerves in the study (or 52.9% of those in patients followed up for a full year) with Parsonage-Turner syndrome (acute brachial neuritis) had achieved complete electrodiagnostic recovery.[47]

Bilateral disease has a less favorable outcome than does unilateral disease, while lower trunk lesions have a less favorable prognosis than do upper trunk lesions.

The rate of recurrence in the inherited form is approximately 75%. The recurrence in the idiopathic form is thought to be between 5% and 26%.[48]