Brachial Neuritis

Etiology

The etiology of brachial neuritis remains unclear, although most experts believe immune-mediated conditions are the primary underlying cause and contributory factors that may predispose certain patients to develop this neuromuscular disorder. The identities of these susceptibilities have not been determined. Mechanical and genetic etiologies have also been associated with brachial neuralgia.[3] 

Any condition that may affect the immune system has been seen in studies to precipitate the onset of brachial neuritis in more than 50% of diagnosed patients.[1] Common immunologic triggers reported in the literature include infection (eg, hepatitis E virus, coxsackie viruses, Covid-19 virus, Escherichia coli, Staphylococcus aureus, and Aspergillus), surgery, connective tissue disorders, systemic lupus erythematosus, temporal arteritis, immunizations, pregnancy, and radiation therapy.[3][1] Hepatitis E virus is one of the most commonly associated viral etiologies, identified in 10% of patients diagnosed with brachial neuritis.[3][1][4] 

Mechanical stress on peripheral nerves is also a probable etiology of brachial neuritis. A history of intense upper-body exercise was identified in 10% of patients with brachial neuritis. Trauma to the shoulder girdle and heavy labor are other types of mechanical injury.[3][1] Additionally, recurrent brachial neuritis has been associated with a family history of the condition. Therefore, experts believe an autosomally dominant form of brachial neuritis, known as hereditary neuralgic amyotrophy (HNA), indicates an underlying genetic cause in some patients.[5] Point mutations and duplications on the SEPT9 gene have been linked to more than half of patients with HNA, though how this predisposes individuals to develop the condition is unknown.[3][1]

Epidemiology

Brachial neuritis mostly affects middle-aged males, with 40 years being the average age of onset, although male and female patients of any age may be affected. However, in HNA, the average age of onset is 20 years. The reported incidence of brachial neuritis is 1 in 1000 individuals, which is higher than previously reported.[2][3] In some studies, the incidence in pediatric populations is higher in neonates and adolescents. In 25% of patients, recurrent brachial neuritis occurs within 5 to 10 years of initial symptoms. The recurrence rate in patients with HNA is higher, reported to be 75%.[3][1]

Pathophysiology

Although the pathophysiology of brachial neuritis is not exactly known, in several studies, an immune-mediated mechanism appears to be involved by directly affecting the brachial plexus or activating an indirect autoimmune response.[4] Even in mechanical etiologies, some experts believe the immune system is involved secondary to the impairment of the blood–nerve barrier, allowing inflammatory mediators to cause damage to brachial plexus nerves. Additionally, ischemia caused by either a mechanical or an inflammatory cause is thought to be related to the onset of sudden extreme pain in patients with brachial neuritis.[4][3][1]

Histopathology

Although the amount of data is sparse, there has been a report of brachial plexus biopsies done in patients with sporadic brachial neuritis, which shows mononuclear inflammatory infiltrates.[5] Furthermore, nerve biopsies that were done in postsurgical patients with brachial neuritis demonstrated neovascularization, perineural thickening, and focal fiber loss, suggesting ischemic changes that point to possible immune pathogenesis.[4] Additionally, peripheral nerve biopsies in patients with brachial neuritis also had T-cell infiltrates in the endothelial vessels around the nerves.[1]

History and Physical

Brachial neuritis is primarily clinically diagnosed based on characteristic clinical features. The clinical course of brachial neuritis is generally divided into the acute and chronic phases. Therefore, patients may vary in their symptomatology depending on which phase they present. Furthermore, brachial neuritis can affect multiple nerves in differing locations to various degrees, resulting in a condition with a broad range of manifestations.[3][1]

Clinical Symptoms

In 70% of patients with brachial neuritis, acute symptoms include severe shoulder pain followed within days to weeks by muscular weakness. The pain is usually unilateral, sudden in onset, and continuous with a burning, sharp, or throbbing quality. Frequently, pain symptoms are located in the lateral aspect of the shoulder, the scapula, the superolateral thoracic wall, and the antecubital fossa that often also radiates to the neck and lateral forearm secondary to involvement of the axillary, suprascapular, anterior interosseous, long thoracic, and musculocutaneous nerves. Commonly, patients wake from sleep due to the pain increasing in severity at night and unrelieved by positional changes.[3][1]

The acute pain is self-limited and subsides after an average of 4 weeks. Rarely the pain can resolve within 24 hours; conversely, 10% of patients with brachial neuritis will have pain for more than 8 weeks.[1] In general, the longer the pain lasts, the longer symptom resolution takes. Typically, patients will develop shoulder and arm weakness after the pain resolves. The forearm and hands can also be involved but are much less common. This clinical course of shoulder pain followed by muscular weakness is a differentiating characteristic of brachial neuritis. In about 30% of patients, muscular weakness will occur within 24 hours of pain onset, though in most patients, weakness is observed after a few weeks from the onset of pain. Some patients also demonstrate sensory deficits; these are rarely the only symptoms present. Diaphragmatic dysfunction, orthopnea, and severe fatigue may also be noted if the phrenic nerve is affected. In the chronic phase of brachial neuritis, clinical features are characterized by continued pain, sensory deficits, and musculoskeletal impairment. Some patients may also have atrophy of the muscles with a slow and steady recovery of muscle function after 6 to 18 months.[3][1][5]

Physical Examination Findings

On physical examination, a thorough neurologic evaluation should be performed. Scapular movement with abduction and anteflexion and strength testing of the shoulder should be assessed. One unique characteristic differentiating brachial plexus neuritis from other conditions is the involvement of the muscles innervated by the same peripheral nerve (ie, pathy paresis). Lower motor neuron signs can be appreciated later in the progress of the disease (eg, hypotonia, areflexia, atrophy, and fasciculations), mainly in the upper brachial plexus (ie, C5-C7 vertebral levels). With weakness after the acute pain phase, findings of decreased shoulder abduction and external rotation may be noted, indicating the involvement of the deltoids, supraspinatus, and infraspinatus muscles. When the long thoracic nerve is involved, medial scapular winging occurs. Sensory changes can also occur in about 78% of patients, consisting of paresthesias and hypoesthesia over the lateral arm, deltoids, and radial forearm. However, patients may not notice sensory changes due to severe pain until an examination is performed.[3][1]

Evaluation

Because clinicians often misdiagnose brachial neuritis due to the similarities with other conditions (eg, rotator cuff tendonitis, cervical cord compression, or nerve entrapment), recognizing the clinical features of brachial neuritis as well as the studies that may help to confirm the diagnosis is essential. Accurate diagnosis is critical to avoiding unnecessary treatments. Although brachial neuritis is primarily a clinical diagnosis, diagnostic studies can provide supportive evidence and exclude differential diagnoses.

Nerve Conduction and Electromyography Studies

Nerve conduction and electromyography studies (EMG) are beneficial in confirming a clinical diagnosis of brachial neuritis and eliminating differential diagnoses, especially in patients with atypical symptoms. However, abnormalities in these studies are typically not apparent initially. On average, nerve conduction studies can take 1 week to demonstrate abnormal findings, while EMG can take 4 weeks. In 30% to 45% of patients, findings of brachial neuritis in nerve conduction studies include reduced amplitudes of action potentials and an inability to localize specific nerve branches. Since brachial neuritis is an axonal disorder, nerve conduction velocities and distal latencies are normal, which helps to exclude demyelination disorders.[1][3] EMG studies are useful in localizing and assessing the severity of nerve damage. In EMG studies, acute denervation with fibrillation potentials and positive sharp waves for nerve roots and peripheral nerves are frequent findings of brachial neuritis 3 to 4 weeks after symptom onset. In later stages of brachial neuritis, approximately 3 to 4 months after symptoms, EMG studies often demonstrate chronic denervation and polyphasic motor unit potentials with early reinnervation. Additional EMG findings include prolonged motor latency and reduced movement amplitude, while sensory testing reveals decreased amplitude with normal conduction velocity.[1][3][6]

Imaging Studies

Gadolinium-enhanced magnetic resonance imaging (MRI) of the shoulder and spine can be utilized to evaluate brachial neuritis. The affected nerves will characteristically have a hyperintense signal indicating inflammation or "hourglass" constrictions. Non-contrast-enhanced MRI may be used to assess for spine or shoulder structural abnormalities; however, the brachial plexus typically appears normal.[1][3] Recent studies have also shown that ultrasound imaging of the involved nerves may also demonstrate abnormal findings. The primary findings of brachial neuritis on ultrasound imaging included focal or diffuse nerve enlargement, incomplete or complete nerve constriction, hourglass nerves, and nerve entanglement.[7]

Laboratory Studies

Serum laboratory studies, including complete blood count and erythrocyte sedimentation rate, have normal findings in patients with brachial neuritis and are typically primarily used to exclude differential diagnoses. Similarly, cerebrospinal fluid analysis is typically normal or, in some patients, may reveal a mild elevation of white blood cells and is mainly used to assess for alternative etiologies. Further evaluation may include tests for Epstein-Barr virus, varicella-zoster, dengue, and hepatitis E.[1][3]

Treatment / Management

Brachial neuritis is a self-limiting condition that often spontaneously resolves. However, several therapies have been used to help alleviate symptoms and improve long-term outcomes. The management approach is divided into acute and chronic phases, with therapies varying depending on the progression of symptoms. However, management often includes supportive therapies, physical therapy, corticosteroids, and intravenous immunoglobulin. Most of these treatment modalities are based on case studies, and evidence of their effectiveness is lacking. In particular, pharmacologic therapies (eg, opioids and corticosteroids) are typically used during the acute phase of the condition. Still, the benefit for long-term outcomes or chronic phase symptoms is debated. Typically, pharmacologic therapies must be combined with other treatment modalities to manage symptoms.[8][1] In some patients, surgical procedures such as neurolysis may be considered.(B2)

Acute Phase Management

Pain management: Initially, severe pain should be treated with analgesics (eg, opioids and nonsteroidal anti-inflammatory medications). Adjuvant neuropathic pain medications (eg, tricyclic or antiepileptic) are usually not as effective due to their slow onset.[5][3] A relatively fast-acting analgesic is needed since the acute pain phase is typically short. After approximately 8 weeks, pain symptoms typically have begun to resolve, and pain medication may not be needed as much.[9][3] Corticosteroids and intravenous immunoglobulin also help in the acute phase and have been shown to lead to a faster resolution of acute pain. However, these medications have not been as effective after the first 2 weeks.[3](B3)

Immobilization therapy: In the acute phase, movement restriction of the affected extremity is utilized to improve severe pain and avoid aggravating symptoms. Immobilization can be discontinued when the pain begins to resolve.[9][3](B3)

Chronic Phase Management

Physical and occupational therapy: Range of motion, strengthening, and stretching exercises are essential once the pain is under control. Physical therapy is primarily effective in improving motor function. Occupational therapy techniques teach patients adaptive strategies to perform self-care activities, household chores, and athletic exercises. Occupational therapists may also enable patients to return to work with more specific activities.[3] Strengthening exercises are not recommended for completely denervated muscles, and the role of electrical stimulation is controversial but should be considered when the denervated state persists for more than 4 months. A follow-up EMG of the involved muscles can show the extent of reinnervation.[10][11](B3)

Surgical therapy: Generally, conservative therapies should be used for 3 months as symptoms often spontaneously resolve. Neurolysis or nerve transfer may be performed in patients who have persistent symptoms. In 90% of the patients, neurolysis improves symptoms.[3] Some experts recommend using the amount of nerve constriction to determine if neurolysis or nerve grafting should be performed. If the nerve constriction is less than 75%, intrafascicular neurolysis is recommended, but nerve grafting may be considered if constriction is ≥75%. Another review recommended neurolysis if paralysis persisted for more than 6 months, whereas nerve or tendon transfers should be considered if neurolysis is contraindicated.[1][3](B3)

Differential Diagnosis

Conditions with clinical features similar to brachial neuritis include:[3]

• Cervical root lesion
• Mononeuritis multiplex
• Multifocal motor neuropathy
• Tumors of brachial plexus
• Transverse myelitis
• Amyotrophic lateral sclerosis
• Herpes zoster Adhesive capsulitis
• Acute calcific tendinitis
• Superior sulcus tumor
• Complex regional pain syndrome
• Myocardial infarction
• Pulmonary embolism
• Rotator cuff tear
• Entrapment neuropathy [3]

Prognosis

Generally, the prognosis of patients with brachial neuritis depends on the extent of nerve damage and reinnervation. One small study reported recovery of most nerve function within 2 to 3 years, though >70% of patients still have some degree of weakness or other residual symptoms.[1] Furthermore, most patients had persistent symptoms and could not return to work in the first 6 months of symptoms onset; however, after 3 years, 7.7% of patients reported complete recovery, and 26.7% were unable to work.[2] Evidence in another study indicated that the prognosis of brachial neuritis is improved in patients who receive timely, adequate treatment.[2] Additionally, children appear to have a better prognosis than adults, most likely due to the higher degree of nerve plasticity in children.[3]

Diagnostic studies may help clinicians determine patient prognosis. EMG studies demonstrating reduced amplitude of motor action potentials >70% are associated with a poor prognosis, indicating only partial reinnervation.[1] Another study found diagnostic ultrasound findings of hourglass constrictions and fascicular entwinement were indications of severe nerve damage and associated with a poorer prognosis.[12]

Complications

Although most patients have some degree of recovery from brachial neuritis, complications are not uncommon. Because of the atrophy and weakness associated with brachial neuritis, patients can have joint instability in the shoulders, wrist, and hands. Because of this, the risk of subluxation or impingement is higher. Adhesive capsulitis of the shoulder could also result in pain and limited range of motion. Patients with persistent residual pain and weakness can also have trouble doing everyday tasks, including reaching or lifting objects or doing repetitive tasks with their shoulders and arms. Additionally, patients who have recurrent brachial neuritis are at a higher risk of complications.