Neuralgic Amyotrophy 

Neuralgic Amyotrophy – Introduction

• Neuralgic Amyotrophy is a rare disease, uncommon syndrome of severe shoulder and upper arm pain followed by significant weakness of upper arm⁽¹⁾

Also Called

•  Parsonage-Turner syndrome
•  Parsonage-Aldren-Turner syndrome
•  acute brachial plexus neuritis
•  acute brachial neuropathy
•  acute brachial plexitis
•  brachial plexus neuropathy
•  idiopathic brachial plexopathy
•  cryptogenic brachial neuropathy
•  idiopathic brachial neuritis
•  paralytic brachial neuritis
•  multiple neuritis of the shoulder girdle
•  local neuritis of the shoulder girdle
•  shoulder girdle neuritis
•  shoulder girdle syndrome
•  serum neuritis

Types

•  sporadic (idiopathic)⁽²⁾
•  hereditary neuralgic amyotrophy – autosomal dominant trait with recurrent attacks of peripheral nerve damage⁽²⁾

Epidemiology

Who Is Most Affected

•  most cases occur in patients aged 20-60 years⁽¹⁾
•  male to female ratio 2:1 to 11.5:1⁽¹⁾

Incidence/Prevalence

•  annual incidence 2-3 cases/100,000 persons⁽²⁾

Possible Risk Factors

•  about 15% of cases are after vaccinations (including influenza and hepatitis B)⁽¹⁾
•  case reports of brachial neuritis after tetanus toxoid immunization in adults and infants can be found in American Academy of Neurology (AAN) Therapeutics and Technology Assessment (Neurology 1999 May 12;52(8):1546)
• other antecedent events include⁽²⁾
  •  prior infection
  •  exercise
  •  peripartum state
  •  stress
  •  trauma
•  case series of neuralgic amyotrophy in 6 patients following cervical decompression surgery can be found in Neurosurgery 2010 Dec;67(6):E1831
• case report of neuralgic amyotrophy following COVID-19 in 52 year old man can be found in Muscle Nerve 2020 Jul 25 early online
•  case report of arteritis and brachial plexus neuropathy as delayed complication of radiation therapy can be found in Mayo Clin Proc 2001 Aug;76(8):849

Associated Conditions

• involvement of nerves beyond brachial plexus⁽²⁾
  •  based on series of 246 patients with neuralgic amyotrophy
  • comparing patients with hereditary form vs. idiopathic form
    •  nerve involvement (either single nerves or combinations) outside brachial plexus in 56% vs. 17%
    •  lumbosacral plexus in 33% vs. 8%
    •  phrenic nerve in 14% vs. 7%
    •  recurrent laryngeal nerve in 19% vs. 2%
    •  other nerve involvement in 7% vs. 3%

Etiology and Pathogenesis

Causes

•  hereditary neuralgic amyotrophy reported to be associated with mutation in septin 9 gene on chromosome 17q25⁽³⁾
•  idiopathic neuralgic amyotrophy is of unknown cause, but may be related to immune-mediated disorder (Neurosurgery 2010 Dec;67(6):E1831)

History and Physical

History

Chief Concern (CC)

•  severe pain in shoulder and upper arm⁽¹⁾
• distribution of pain^(2,3)
  •  in most patients located in shoulder or neck and/or radiating to arm (mimicking radicular-type pain)
  • less common presentations of pain
    •  scapular region or back and/or radiating to chest wall or arm
    •  medial arm and/or hand and axilla
    •  pain in restricted areas (such as neck, scapula, chest wall)
  •  pain and symptoms usually on one side, but can be bilateral in 30% of cases
  •  if bilateral, then often asymmetric, with onset usually occurring simultaneously or within 24 hours
• sensory symptoms in 69% of patients⁽²⁾
  •  decreased sensation in 46%
  •  combination of decreased sensation and paresthesias in 39%
  •  paresthesias in 14.2%
  •  allodynia (pain in response to sensory stimulus) in 0.5%

History of Present Illness (HPI)

•  typical sequence of severe pain in upper arm and shoulder followed by weakness⁽¹⁾
• pain⁽²⁾
  •  onset usually during evening or night
  •  duration is days to weeks
  •  initial pain continuous, usually worse at night and severe enough to cause sleep disturbance in most patients
  •  initial pain often followed by severe neuropathic stabbing or shooting pain which may be triggered by arm movement (lasts weeks to months)
  •  may have a musculoskeletal-type pain during recovery (especially in periscapular, cervical and occipital regions)
• weakness⁽²⁾
  • onset of weakness in attacks presenting with initial pain
    •  within first week in 73% of patients
    •  1-2 weeks in 14% of patients
    •  > 2 weeks in 27%
  •  weakness may continue to progress over months
•  weakness may progress to become severe with totally flaccid muscles⁽¹⁾
• alternative presentations may include⁽²⁾
  •  painless attacks in 4%
  •  weakness preceding pain in 3%
  • involvement of other nerves in 22% including
    •  phrenic nerve
    •  lumbosacral plexus

Family History (FH)

•  in series of 246 patients with neuralgic amyotrophy, 19% had family history⁽²⁾

Physical

General Physical

•  muscle atrophy during attack seen in 89% males and 75% females⁽²⁾

Skin

• vasomotor changes may be found⁽²⁾
  •  corresponding to areas with sensory or motor loss
  • skin changes can include
    •  trophic changes (skin may become shiny and smooth)
    •  edema
    •  temperature dysregulation (including increased sweating)
    •  changes in hair or nail growth

Neuro

•  may be bilateral in up to 30% of patients⁽¹⁾
• sensory disturbance
  •  found on exam in most patients⁽²⁾
  •  distribution may be patchy⁽¹⁾
  •  does not correspond to single nerve root dermatome⁽¹⁾
  •  most common distribution is decreased sensation over deltoid and lateral upper arm⁽²⁾
•  most common pattern of weakness is upper brachial plexus with involvement of long thoracic nerve (serratus anterior causing winging of scapula)⁽¹⁾
• distribution of weakness in series of 246 patients⁽²⁾
  • upper part of brachial plexus in 71%
    •  with long thoracic nerve involvement (winging of scapula) in 50%
    •  without long thoracic nerve involvement in 21%
  • most commonly affected muscles include
    •  infraspinatus
    •  serratus anterior (winging of scapula)
    •  supraspinatus
    •  biceps
    •  rhomboids
    •  pronator teres
  • other frequently affected muscles
    •  brachioradialis
    •  wrist extensors
    •  deltoid
    •  triceps
    •  wrist flexors
    •  finger extensors

Diagnosis

Making the Diagnosis

•  clinical suspicion based on sequence of severe pain in shoulder and arm followed by weakness usually developing within 1 week⁽¹⁾
•  pattern of pain and weakness is not consistent with cervical radiculopathy⁽¹⁾
•  confirmation by electrophysiologic studies (although should be performed 3-4 weeks after onset of syndrome)⁽¹⁾

Differential Diagnosis

•  cervical radicular pain and radiculopathy⁽¹⁾
• rotator cuff injury⁽¹⁾
  • rotator cuff tear
  • rotator cuff impingement
• hereditary neuropathy with liability to pressure palsies
  •  associated with PMP22 deletion⁽²⁾
  •  autosomal dominant deletion of 17p11.2 (Mayo Clin Proc 1995 Aug;70(8):743)
•  postoperative C5 palsy following cervical decompression (Neurosurgery 2010 Dec;67(6):E1831)
• other causes of upper extremity pain and weakness
  •  other peripheral nerve injuries (for example, ulnar neuropathy, carpal tunnel syndrome)
  •  mononeuritis multiplex
  •  traction injury of brachial plexus
  •  tumor involving brachial plexus
  •  monomelic amyotrophy (focal lower motor neuron disease of young males mostly in India and Japan)
  • acromioclavicular (AC) joint injuries
  •  shoulder strain
  • traumatic brain injury
  • stroke
  •  brain tumor
  • rotator cuff tear
  • adhesive capsulitis of shoulder
  • transverse myelitis
  • poliomyelitis
  • amyotrophic lateral sclerosis (ALS)
  • herpes zoster
  •  Reference – J Spec Oper Med 2009 Winter;9(1):16PDF as referenced in⁽³⁾

Testing Overview

• electrophysiologic testing (electromyography, nerve conduction velocities) should be performed after 3-4 weeks⁽¹⁾
•  chest x-ray
• magnetic resonance imaging (MRI)
  •  MRI of brachial plexus to rule out brachial plexopathy
  •  MRI of cervical spine often done if suspected diagnosis was radiculopathy

Imaging Studies

• chest x-ray⁽²⁾
  •  may exclude Pancoast tumor
  •  hemidiaphragm may be elevated if phrenic nerve involvement
•  magnetic resonance imaging (MRI) of brachial plexus may show focal hyperintensity and focal thickening of affected areas of plexus⁽²⁾
• MRI may rule out other conditions
  •  may reveal rotator cuff injury, labral tears, impingement injuries or other shoulder problems⁽³⁾
  •  can detect abnormalities in musculature around shoulder⁽³⁾
  •  MRI of neck may be confounding if cervical abnormalities detected that do not correspond to clinical picture^(1,2)
•  American College of Radiology (ACR) Appropriateness Criteria for plexopathy can be found in ACR 2016 PDF

Cerebrospinal Fluid (CSF) Analysis

• abnormal CSF studies may be found in some patients⁽²⁾
  • based on series of 32 patients
    •  elevated protein in 2 patients
    •  elevated protein and slight increase in white blood cells in 1 patient
    •  positive oligoclonal bands in 1 patient
    •  concurrent viral meningitis in 1 patient

Other Diagnostic Testing

• electrophysiologic testing (electromyography, nerve conduction velocities)
  •  should be performed about 3-4 weeks after onset of symptoms⁽¹⁾
  •  may demonstrate chronic denervation and early reinnervation with polyphasic motor units⁽¹⁾
  •  abnormal in almost all patients, with pattern of abnormalities making diagnosis (helpful in localizing lesion to brachial plexus and distinguishing from cervical lesion)^(2,3)
•  review of electrodiagnostic testing can be found in Cleve Clin J Med 2005 Jan;72(1):37PDF

Management

Management Overview

• no randomized trials identified evaluating any treatment for idiopathic or hereditary neuralgic amyotrophy
• treatment of pain may include
  • avoiding triggering movement and postures
  •  applying local warmth
  • medications – analgesics and corticosteroids

Activity

•  initial pain may be partially relieved by avoiding triggering movements and postures⁽²⁾
•  applying warm compresses gave pain relief in 68% of 38 patients⁽²⁾
•  if significant weakness in deltoid muscle, use of sling may help to avoid subluxation of humerus (Am Fam Physician 2000 Nov 1;62(9):2067full-text)
•  physical therapy and exercises often recommended although no evidence for benefit⁽³⁾

Medications

• response to medications used for initial pain relief in series of 246 patients ⁽²⁾
  •  acetaminophen associated with either good relief or some relief in 80% of 5 patients
  •  nonsteroidal anti-inflammatory drugs (NSAIDs) associated with either good relief or some relief in 45.7% of 46 patients
  •  opioids (including tramadol) associated with either good relief or some relief in 84.2% of 19 patients
  •  NSAIDs with an opioid associated with either good relief or some relief in 100% of 28 patients
  •  any medication along with either amitriptyline, carbamazepine or gabapentin associated with either good relief or some relief in 73.9% of 23 patients
• corticosteroids reported to reduce time to improvement and decrease risk of recurrent attacks⁽²⁾

Other Management

• no randomized or quasi-randomized trials identified evaluating any treatment for idiopathic or hereditary neuralgic amyotrophy
  •  based on Cochrane review
  •  Reference – Cochrane Database Syst Rev 2009 Jul 8;(3):CD006976 (review updated 2011 Nov 9)
• patients with post cervical decompression neuralgic amyotrophy reported to recover with pain management and physical therapy (level 3 [lacking direct] evidence)
  •  based on case series
  •  6 patients who developed neuralgic amyotrophy after anterior cervical spine decompression were referred to a specialty center and followed for 2 years
  •  4 patients had recovery of motor strength and pain improvement after pain management and physical therapy alone
  •  1 patient had multiple nerve releases (ulnar nerve transposition, radial tunnel release, carpal tunnel release, Guyon canal release) and had improvement in symptoms
  •  1 patient had bilateral spinal accessory nerve to suprascapular nerve transfer
  •  Reference – Neurosurgery 2010 Dec;67(6):E1831

Complications and Prognosis

Complications

•  recurrent attacks occurred in 74.5% of patients with hereditary form and in 26.1% with idiopathic form⁽²⁾
• orthopedic complications in series of 246 patients⁽²⁾
  • frozen shoulder (glenohumeral adhesive capsulitis) in 17%
  •  glenohumeral subluxation in 8.4%
  •  contractures in fingers or wrist in 9.6%
•  long-term pain or weakness⁽²⁾

Prognosis

• onset of motor recovery⁽²⁾
  •  within 6 months in 68%
  •  6-12 months in 19%
  •  1-2 years in 9%
  •  2-3 years in 5%
• sensory recovery⁽²⁾
  •  no recovery in 51% patients
  •  full recovery in 29%
  •  moderate recovery in 20%
• persistent pain ≥ 3 years⁽²⁾
  •  neuropathic pain in about 25% of patients
  •  musculoskeletal pain in about 60% of patients
• recurrence rates⁽²⁾
  •  26% in patients with idiopathic neuralgic amyotrophy
  •  75% in patients with hereditary neuralgic amyotrophy
• patients with hereditary neuralgic amyotrophy reported to have more severe disease than patients with idiopathic neuralgic amyotrophy⁽²⁾
  • patients with hereditary neuralgic amyotrophy more likely to have
    •  earlier age of onset
    •  increased number of attacks
    •  more involvement of nerves outside the brachial plexus
    •  increased pain
    •  increased severity of weakness
    •  worse functional outcomes
    •  increased sick leave

Prevention and Screening

•  not applicable

Guidelines and Resources

Guidelines

• American College of Radiology (ACR) Appropriateness Criteria for plexopathy can be found at ACR 2016 PDF

Review Articles

• review can be found in J Neurol Neurosurg Psychiatry 2020 Aug;91(8):879
• review can be found in Muscle Nerve 2016 Mar;53(3):337
•  review can be found in Phys Med Rehabil Clin N Am 2014 May;25(2):265
•  review of acute brachial plexus neuritis can be found in Am Fam Physician 2000 Nov 1;62(9):2067
•  review of nerve injury from trauma to neck and shoulder can be found in Am Fam Physician 1999 Nov 1;60(7):2035
•  review of neuralgic amyotrophy after surgery can be found in Aesthetic Plast Surg 1996 May-Jun;20(3):263
•  review of brachial plexopathies can be found in Muscle Nerve 2004 Nov;30(5):547

MEDLINE Search

•  to search MEDLINE for (Neuralgic amyotrophy) with targeted search (Clinical Queries), click therapy, diagnosis, or prognosis

Patient Information

•  DynaMed Editors have not identified patient education materials that meet our criteria for inclusion (freely accessible, nonpromotional, topic-specific). We will continue to search for acceptable materials and welcome your suggestions.

References

General References Used

1. Stutz CM. Neuralgic amyotrophy: Parsonage-Turner Syndrome. J Hand Surg Am. 2010 Dec;35(12):2104-6.
2. van Alfen N, van Engelen BG. The clinical spectrum of neuralgic amyotrophy in 246 cases. Brain. 2006 Feb;129(Pt 2):438-50.full-text.
3. Sathasivam S, Lecky B, Manohar R, Selvan A. Neuralgic amyotrophy. J Bone Joint Surg Br. 2008 May;90(5):550-3.