summary Brachial neuritis (Parsonage-Turner syndrome) is an uncommon disorder characterized by severe shoulder pain followed by patchy muscle paralysis and sensory loss involving the shoulder girdle and upper extremity. Diagnosis is made clinically with a through neurological exam that may vary from moderate motorsensory changes to flaccid paralysis of the upper extremity and can be confirmed by EMG/NCS. Treatment is observation and pain control with recovery taking up to 3 years. Operative nerve exploration, neurolysis, nerve transfer or tendon transfer be be indicated if there is no evidence of EMG recovery by 9-12 months. Epidemiology Incidence 1.6-3 cases per 100,000 persons reported per year likely at least 30 cases per year (underdiagnosed) Demographics males > females (range 1.5:1 to 11.5:1) middle-age (4th decade) ages 20-60 most common (average age 41), though any age can be affected (range 3-81 years old) unilateral involvement bilateral in 10-30% of patients (16% simultaneously) Etiology Two clinical types idiopathic neuralgic amyotrophy (INA) (this topic) hereditary neuralgic amyotrophy (HNA) (see associated conditions) Various eponyms for this syndrome include: scapular winging (when long thoracic nerve involved) neuralgic amyotrophy (NA) or idiopathic neuralgic amyotrophy (INA) Parsonage-Turner syndrome (PTS) acute brachial neuropathy / neuritis / plexopathy / plexitis idiopathic brachial plexus neuropathy / neuritis Pathophysiology pathoanatomy any nerve or branch within the brachial plexus can be involved nerves outside the brachial plexus are affected in 17% of cases nerves most commonly affected long thoracic nerve - can cause scapular winging suprascapular nerve axillary nerve musculocutaneous nerve radial nerve other: cervical roots, anterior interosseous nerve (AIN), posterior interosseous nerve (PIN), lateral antebrachial cutaneous nerve (LABC) pathophysiology unclear etiology for idiopathic type, likely multifactorial with autoimmune, genetic, infectious, environmental and biomechanial processes all playing a role autoimmune increased blastogenic activity of lymphocytes transform to larger more active lymphocytes when in contact with brachial plexus tissue increased complement-fixing antibodies to peripheral nerve myelin biomechanical mobility of the upper trunk predisposes to wear-and-tear on the blood-nerve barrier in this region repetitive mobilization of the upper extremity (strenuous exercise, heavy manual labor) may disrupt the blood-nerve barrier that normally prevents immune factors from contacting the peripheral nerve system ultimately, a constellation of processes results in an inflammatory response involving the brachial plexus and its branches risk factors infection viral infections (25-55%) Ebstein-Barr (EBV), varicella-zoster, Coxsackie B, parvovirus B19, cytomegalovirus (CMV), mumps, smallpox, HIV bacterial infections Leptospira, TB, Yersinia, Salmonella, Borrelia burgdorferi immunizations (15%) Tetanus, hepatitis B stress perioperative and peripartum (14%) strenuous exercise (8%) burns drugs abacavir, streptokinase, heroin, infliximab, interferon iatrogenic interscalene block, surgery, lumbar punctures, irradiation Associated conditions hereditary neuralgic amyotrophy (HNA) very rare ~200 families worldwide autosomal dominant mutations in the gene septin 9 on chromosome 17q24 cytoskeleton protein highly expressed in glial cells in neuronal tissue differs from idiopathic form by dysmorphic features short stature, hypotelorism, cleft palate, facial asymmetry, unusual skin folds higher incidence of recurrent episodes precipitated similarly to those with INA younger age of onset childhood and adolescent (average age 28) frequent involvement of nerves outside the brachial plexus (56%) most commonly lower cranial nerves (CN VII, IX, X, XI and XII) other: lumbosacral plexus, phrenic and recurrent laryngeal nerves more severe paresis worse functional outcome Classification Idiopathic Neuralgic Amyotrophy (INA) vs. Hereditary Neuralgic Amyotrophy (HNA) Factor INA HNA Incidence 1-30/100,000/yr Rare Gene Septin 9 (chromosome 17) Age at Onset Middle-age (20-60 y/o) Young (20s) Recurrence Uncommon (~1.5 episodes) More frequent (3.5 episodes) Appearance Normal features Dysmorphic Involvement of Nerves outside Brachial Plexus Uncommon (17%) Common (56%) Presentation History phase I: sudden onset of severe, unrelenting shoulder pain primary symptom in 90% of cases radiates to the proximal arm and/or neck awakens people from sleep lasts days to weeks persists longer in males (45 days vs. 23 days in females) phase II: painless flaccid paralysis after the onset of pain, a period of weakness begins within 24 hours (33%) to 4 weeks (80%) most commonly involves the upper brachial plexus and usually more than one nerve branch deltoid, supraspinatus, infraspinatus, serratus anterior and the biceps brachii often will see differential involvement of muscles innervated by the same nerve (patchy paresis) highly characteristic finding phase III: slow recovery slow and steady return of motor function over 6-18 months duration over the recovery phase is often directly proportional to duration of pain phase at onset Physical examination fasciculations and atrophy may be seen signs of dennervation during the painful phase, the pain is not particularly affected by motion or palpation severe weakness of shoulder external rotation and abduction supraspinatus, infraspinatus and deltoid dysfunction hypotonia and areflexia signs of lower motor neuron involvement medial scapular winging serratus anterior (long thoracic nerve) involvement sensory changes occur in 78% of patients paresthesias and hypoesthesias most common over deltoid, lateral arm and radial forearm may go unnoticed by patient due to overlying pain and weakness autonomic dysregulation occur in 15% of patients trophic skin changes temperature dysregulation increased sweating altered nail/hair growth Evaluation Diagnostic tests can help rule out other conditions and thus support the diagnosis of INA Laboratory CBC and ESR are usually normal labs are largely inconclusive, but may show elevated liver enzymes positive antiganglioside antibodies positive antinuclear antibody (ANA) test Imaging plain radiographs often normal evaluate for calcific tendinitis of the rotator cuff can also present with severe, incapacitating shoulder pain magnetic resonance imaging (MRI) early findings T2: diffuse signal hyperintensity (edema) within muscles innervated by the brachial plexus supraspinatus, infraspinatus, deltoid and teres minor muscles most commonly exhibit MRI abnormalities late findings T1: focal intramuscular signal intensity (fatty infiltration) and atrophy of the involved muscles Other studies electromyography (EMG) helpful to confirm the diagnosis show findings compatible with INA in 96% of patients findings early (3-4 weeks after symptom onset) acute dennervation with positive sharp waves and fibrillation potentials in both peripheral nerve and nerve root distributions late (3-4 months after symptom onset) chronic dennervation and early reinnervation with polyphasic motor unit potentials sensory nerve conduction studies (NCS) less useful than EMG findings reduced amplitude, preserved conduction velocity and distal latency may be normal normal NCS does not preclude diagnosis of INA cerebrospinal fluid (CSF) analysis findings usually normal mildly elevate protein levels, slight pleocytosis and oligoclonal bands have been reported Differential Cervical spine radiculopathy pain and weakness follows a specific nerve root distribution INA involves multiple nerve roots and peripheral nerve distributions starts in the neck and radiates down the arm INA involves the shoulder and occasionally radiates to the neck and proximal arm pain is aggravated by movement in the acute pain phase, motion does not tend to worsen pain Rotator cuff pathology shoulder pain persists despite development of shoulder weakness in INA, shoulder weakness tends to develop after acute pain phase and is often painless impingement signs are often present pain usually resolves or improves with subacromial lidocaine injection subacromial lidocaine injection does not affect INA pain, as the pain is neuropathic and not related to impingement Entrapment neuropathy shoulder pain with progressive weakness in a specific peripheral nerve distribution (ex. supraspinatus and infraspinatus weakness with suprascapular nerve entrapment) INA usually involves the upper brachial plexus, affecting muscles from multiple peripheral nerve distributions (ex. supraspinatus, infraspinatus, deltoid and biceps weakness) EMG shows involvement of an isolated peripheral nerve EMG in INA shows involvement of nerve roots and peripheral nerves Idiopathic hypertrophic brachial neuritis (IHBN) rare disorder characterized by weakness in upper limb muscles and hypertrophy of the brachial plexus brachial plexus hypertrophy can be seen on MRI typically painless INA begins with acute painful phase, followed by painless weakness EMG and NCS exhibit demyelination (slowed velocity, prolonged distal sensory latencies) NCS in INA shows reduced amplitude related to axonal loss, but preserved conduction velocity and distal sensory latencies (no demyelination) Treatment Nonoperative observation and pain control indications mainstay of treatment technique during the early pain phase, pain control is paramount NSAIDs judicious use of narcotic medications immobilization oral corticosteroids (see below) follow patients monthly for improvement can use both physical exam and serial EMGs to follow neurologic recovery outcomes at 1 year, observation alone results in similar functional outcomes compared to observation with physical therapy prognosis is good with most patients making a complete recovery, but progress is slow at 1 year, only 35% of patients have recovered at 3 years, 90% of patients have recovered full muscle strength and function with no residual pain or deficits physical therapy indications once severe pain has abated and weakness is the primary issue technique shoulder girdle strengthening and range of motion pain relief strategies to alleviate traction on the involved nerves outcomes reverses atrophy and improves muscle bulk comparable to contralateral unaffected side oral corticosteroids indications severe pain during early pain phase technique two week course of 1mg/kg/day of prednisone followed by a two week taper outcomes some evidence that this regimen may lead to a more rapid resolution of the pain phase, but does not affect the progression or prognosis Operative nerve exploration, neurolysis, neurorrhaphy, nerve grafting, nerve transfer or muscle/tendon transfers indications no evidence of regeneration or early recovery in a nerve distribution by 6-9 months on physical examination and EMG studies technique neurolysis long thoracic nerve microneurolysis ulnar nerve transposition, Guyon canal release radial tunnel release carpal tunnel release neurorrhaphy and nerve grafting excision of diseased nerve segment and either direct repair (neurorrhaphy) or nerve grafting nerve transfers muscle / tendon transfers split pectoralis major transfer for serratus anterior paralysis outcomes surgical exploration of patients with INA without neurologic recovery revealed hourglass-like constrictions in the peripheral nerves with no external compression neurolysis alone was superior to neurorrhaphy and nerve grafting Prognosis Recurrence is rare in non-hereditary cases Factors associated with poor prognosis female gender lower trunk involvement upper trunk has best prognosis persistent pain and no motor function recovery by 3 months hereditary cases Age has no effect on prognosis Timing of recovery 66% have recovery of motor function within 1 month recovery rated "excellent" in 36% at 1 year, 75% at 2 years and 89% at 3 years may take up to 8 years for full recovery of strength