Quantcast
Last updated on April 20, 2014 at 17:20 EDT

Neuralgic Amyotrophy

May 21, 2008

By Sathasivam, S Lecky, B; Manohar, R; Selvan, A

Neuralgic amyotrophy is an uncommon condition characterised by the acute onset of severe pain in the shoulder and arm, followed by weakness and atrophy of the affected muscles, and sensory loss as the pain subsides. The diversity of its clinical manifestations means that it may present to a variety of different specialties within medicine. This article describes the epidemiology, aetiopathogenesis, clinical features, differential diagnoses, investigations, treatment, course and prognosis of the condition. Neuralgic amyotrophy was described by Dreschfeld in 1887.1 He reported recurrent episodes of the condition in two sisters.1 Several other reports followed,2-6 but it was Parsonage and Turner7 who clearly detailed the clinical aspects of the condition in a cohort of 136 patients in 1948. Many case reports and series of patients with neuralgic amyotrophy have been described, expanding the clinical variants and nomenclature. It has been referred to as the Parsonage-Turner syndrome, acute brachial neuropathy, acute brachial plexitis, brachial plexus neuropathy, cryptogenic brachial neuropathy, idiopathic brachial plexopathy, idiopathic brachial neuritis, localised neuritis of the shoulder girdle, multiple neuritis of the shoulder girdle, paralytic brachial neuritis, serum neuritis, shoulder girdle neuritis and the shoulder girdle syndrome.

The diversity of presenting features means that patients with neuralgic amyotrophy may be seen by orthopaedic surgeons, neurosurgeons, neurologists, internal medicine physicians, accident and emergency physicians, general practitioners, sports medicine specialists, obstetricians and respiratory physicians.

Epidemiology

The incidence of neuralgic amyotrophy is approximately two to three per 100 000 person-years.8,9 It has been described in patients aged between three months10 and 81 years,11 with the highest incidence occurring in the third and seventh decades.10-12 Males are more commonly affected than females in ratios ranging between 2:1 and 11.5:1.10,13

Aetiology

Neuralgic amyotrophy exists as an idiopathic and a hereditary form. Although the aetiology of the idiopathic form is unknown, various antecedent events, or factors which may trigger an immune- mediated process, have been proposed to contribute to its development. Infection has preceded the development of symptoms in 25% to 55% of patients.10,13-15 A history of antecedent immunisation has been recorded in 15% of cases.7,10 Strenuous exercise has been undertaken prior to the onset of symptoms in approximately 8% of cases in two large series.10,16 Post-surgical neuralgic amyotrophy is well-recognised after operations in areas remote from the shoulder girdle.6,7,16,17 It has occurred during pregnancy andpostpartum.14,16,18,19

Idiopathic neuralgic amyotrophy may be a result of an autoimmune process. A study showed that lymphocytes of patients with the condition increased their blastogenic activity in cultures with nerve extracts from different nerves of the brachial plexus and their branches, but not in cultures with extracts of nerves from the sacral plexus.20 Another study showed an increase in complement- fixing antibodies to peripheral nerve myelin in the acute phase in three patients with neuralgic amyotrophy.21 The results of these two studies have yet to be replicated.22

The hereditary form of the condition is an autosomal dominant recurrent neuropathy affecting the brachial plexus. It is the first monogenic disease caused by defects in a septin family gene. Mutations in the gene septin 9 on chromosome 17q25 have been found in several families with hereditary neuralgic amyotrophy.23 Gene septin 9 is a member of the cytoskeleton-related septin family, which is highly expressed in glial cells in neuronal tissues. Sequence alterations in septin 9 may disrupt various cellular processes, leading to abnormal cytoskeleton events and signalling.24

Table I. Differential diagnoses of neuralgic amyotrophy

Clinical features

The characteristic clinical presentation is an acute, severe burning pain in the shoulder or arm lasting for several days or weeks, followed by muscle weakness, atrophy and sensory loss as the pain diminishes. However, this temporal profile is not universal. Symptomatic bilateral involvement of the brachial plexus occurs in approximately 30% of cases and is usually asymmetrical.7,10,16 Most of these patients note bilateral pain either simultaneously or within 24 hours.25,26 However, it is not uncommon for patients to present with bilateral neuralgic amyotrophy with only one side being symptomatic.27

Pain

Pain was the first symptom in 90% of cases in a study of 246 patients with neuralgic amyotrophy.16 The four loci for initial pain were in the shoulder or radiating from the shoulder to the arm (39.7%), from the neck radiating into the arms (35.4%), from the scapular or posterior chest wall region radiating to the arm or anterior chest wall or both (18.8%), or confined to a distribution in the lower plexus (6.1%). The pain is typically severe and unrelenting, often waking patients from sleep. It is commonly worsened by movement of the shoulder or arm, resulting in patients holding the arm with the elbow flexed and the shoulder adducted.28 A helpful feature in distinguishing neuralgic amyotrophy from cervical radiculopathy is that with a VaIsalva manoeuvre, the aggravation of the pain is typically less in the former.26 The pain may last for more than eight weeks. 6 Minimal or no pain is uncommon in neuralgic amyotrophy.29

Weakness and atrophy

Weakness develops within 24 hours in approximately one third of cases.16 In approximately 70%, it occurs within the first two weeks of the onset of pain.10,16 It characteristically worsens as the pain subsides. Weakness affecting the distribution of the upper part of the brachial plexus, either with or without involvement of the long thoracic nerve is the most common pattern.1,10,16 The muscles commonly affected include the infraspinatus, supraspinatus, serratus anterior, biceps, deltoid and triceps.6,10,13,16,27 [t is well recognised that individual nerves can be affected in isolation or several at a time, mimicking a 'mononeuritis multiplex' pattern.26 This may occur in 75% of cases.14 Isolated involvement of a particular nerve, for example, the anterior interosseous branch of the median nerve, has also been described.30,31 Unilateral or bilateral phrenic neuropathy resulting in paralysis of the diaphragm may occur in isolation or in association with other nerve involvement.32-35 Hemidiaphragmatic paralysis may be present on the contralateral side to the affected extremity. Involvement of cranial nerves VII, IX, X, XI and XII has also been reported.14,34-37

Sensory involvement

Sensory involvement may occur in 78% of cases.16 Hypoaesthesia or a combination of paraesthesia and hypoaesthesia are the most common complaints,"' seen most often over the deltoid and lateral aspect of the upper arm and the radial aspect of the forearm.10,13,16,27 Isolated sensory manifestations have been described in eight patients; in three, the lateral cutaneous nerve of the forearm was affected, while partial involvement of the distal median nerve was documented in the orher five.

Autonomic dysfunction

Signs of involvement of the peripheral autonomic nervous system, such as vegetative and trophic skin changes, oedema at the onset of the attack, temperature dysregulation, increased sweating and changes in nail or hair growth were documented in approximately 15% of a series of 246 cases.16 In addition, one patient with hereditary neuralgic amyotrophy suffered a persistent Horner's syndrome combined with involvement of the brachial plexus.39

Craniofacial and cutaneous findings

Minor dysmorphic features including hypotelorism, palate and unusual skin folds have been observed in some patients with the hereditary form of the condition.40,41

Differential diagnosis

The diagnosis of neuralgic amyotrophy can be challenging, especially in the early stages. There are many differential diagnoses (Table I). It can mimic other conditions which cause acute pain and weakness around the shoulder. The pain can be so severe that patients may be investigated for myocardial infarction. The correct diagnosis is important to avoid unwarranted treatment, including inappropriate surgery.

Investigations

Blood tests occasionally reveal abnormalities including elevated liver enzymes and positive antiganglioside antibodies, '6 although the significance of these remains unclear. Examination of the cerebrospinal fluid is usually normal, although mildly elevated protein, slight pleocytosis and oligoclonal bands have been reported.10,13,16 A chest radiograph is useful to exclude a Pancoast tumour of the lung and may detect an elevated hemidiaphragm caused by involvement of the phrenic nerve. An MRI of the cervical spine may reveal cervical disc disease or cervical root lesions, and of the shoulder may identify other causes of pain at this site such as rotator cuff tears, lahral tears, impingement syndromes or other local lesions. Abnormalities in the musculature of the shoulder girdle related to denervation may be detected. The mechanism and time course of changes in the signal intensity of the muscles on MRI are not fully understood. In the acute phase of denervation, the intensity may be normal.42 The earliest detectable change in denervated muscles is a diffuse increase of the T^sub 2^-weighted signal as a result of oedema, without a T^sub 1^-weighted change.42- 44 In the subacute and chronic stages of denervation, the T^sub 2^- weighted changes persist and muscle atrophy may develop.42,43,45 Atrophy is suggested by a reduced muscle mass and an increase in the intramuscular linear T^sub 1^weighted signal because of fatty infiltration, which may return to normal several months after the chronic stage. An increased T^sub 2^-weighted signal in the supraspinatus, infraspinatus and deltoid muscles at initial presentation and T^sub 1^-weighted changes of atrophy without fatty infiltration during follow-up, were reported in three cases.46 A retrospective study of 27 patients with neuralgic amyotrophy showed T^sub 1^- and T^sub 2^-weighted signal changes in the muscles compatible with predominant involvement of the suprascapular (supraspinatus and infraspinatus) and axillary (deltoid and teres minor) nerves. These changes matched or nearly matched electromyographic changes where these were available." Similarly, in another retrospective study of 26 cases, T^sub 1^- and T^sub 2^- weighted signal changes were most commonly seen in the supraspinatus, infraspinatus, deltoid and teres minor muscles.47 Conventional MRI of the brachial plexus is not sensitive enough to identify pathological changes in neuralgic amyotrophy. Of 50 patients studied in one series, focal T^sub 2^ hyperintensities in two patients and focal thickening of the plexus in one patient were detected.16 Magnetic resonance neurography provides better image resolution. Using this technique in an acute case of neuralgic amyotrophy, the affected brachial plexus was found to be thickened and hyperintense, while in a chronic case there was also hyperintensity.

Electrophysiological evaluation is useful for the diagnosis of neuralgic amyotrophy and to distinguish it from cervical root lesions. It is helpful in localising the symptoms to the brachial plexus. Nerve conduction studies and needle electromyography are best performed at least three weeks after the onset of symptoms.26 Nerve conduction velocities are usually normal, although proximal conduction block has been recorded,50,51 although the primary pathology is thought to be axonal degeneration.10,52 In three of five cases with proximal conduction block, there was complete resolution of the block when the studies were repeated three to nine months later, suggesting that in some cases demyelination may predominate in the early stages.50,51 Delayed distal latencies and a decreased amplitude of compound muscle action potentials may also be seen.14,15,38,53 Electromyography reveals acute denervation, indicating axonal degeneration, with positive sharp waves and fibrillation potentials three to four weeks after the onset of symptoms.14,25,27 Electromyography performed three to four months after the initial symptoms may show chronic denervation and early reinnervation with polyphasic motor unit potentials.54

Treatment

Corticosteroids may reduce the time to the start of improvement of weakness, although treated patients appeared to suffer more attacks than untreated ones. Corticosteroids may reduce pain in the early stages.10,16 Analgesics may also be helpful, with a combination of a non-steroidal anti-inflammatory and an opiate appearing to be best.16 Physiotherapy and rehabilitative exercises are recommended as the pain subsides and the weakness improves,26 although these measures have not been shown to hasten recovery.

Course and prognosis

Some studies have recorded that between 80% and 90% of patients had recovered after two to three years.10,14,55 However, others have suggested a less favourable outcome with less than 50% of patients recovering fully from pain or weakness after six years.16,56 Recurrence has been reported in between 5% and 26% of patients with idiopathic neuralgic amyotrophy,10,16 although referral bias may have affected the study with the higher figure.16

References

1. Dreschfeld J. On some of the rarer forms of muscular atrophies. Brain 1887;9:187-9

2. Feinberg J. Fall von Erb-Klumpke scher: lahmung nach influenza Centralbl 1897;16:588-637.

3. Bramwell E, Struthers JW. Paralysis of the serratus magnus and lower part of the trapezius muscles. Rev Neurol Psychiat 1903;1:717- 30.

4. Richardson JS. Serratus magnus palsy. Lancet 1942;1:618.

5. Wyburn-Mason R. Brachial neuritis occurring in epidemic form. Lancet 1941;1:6623.

6. Spillane JD. Localised neuritis of the shoulder girdle: a report of 46 cases in the MEF. Lancet 1943;2:532-5

7. Parsonage MJ, Turner JWA. Neuralgic amyotrophy: the shoulder- girdle syndrome. Lancet 948;1:973-8.

8. Beghi E, Kurland LT, Mulder DW, Nicolosi A. Brachial plexus neuropathy in the population of Rochester, Minnesota 1970-1981. Ann Neurol 1985;18:320-3.

9. MacDonald BK, Cockerell OC, Sander JW, Shorvon SD. The incidence and lifelime prevalence of neurological disorders in a prospective community-based study in the UK. Brain 2000;123:665-76.

10. Tsairis P, Dyck PJ, Mulder DW. Natural history of brachial plexus neuropathy: report on 99 patients. Arch Neurol 1972;27:109- 17.

11. Gaskin CM, Helms CA. Parsonage-Turner syndrome. MR imaging findings and clinical information of 27 patients. Radiology 2006;240:501-7.

12. van Allen N. The neuralgic amyotrophy consultation. J Neurol 2007;254:695-704.

13. Magee KR, DeJong RN. Paralytic brachial neuritis: discussion of clinical features with review of 23 cases. JAMA 1960;174:1258- 62.

14. Cruz-Martinez A, Barrio M, Arpa J. Neuralgic amyotrophy: variable expression in 40 patients. J Peripher; Nerve Syst 2002;7:198-204.

15. Mullins GM, O'Sullivan SS, Neligan A, et al. Non-traumatic brachial plexopathies, clinical, radiological and neurophysiological findings from a tertiary centre. Clin Neurol Neurosurg 2007;109:661- 6.

16. van Allen N, van Engelen BGM. The clinical spectrum of neuralgic amyotrophy in 246 cases. Brain 2006;129:438-50.

17. Malamut RI, Marques W, England JD, Sumner AJ. Postsurgical idiopathic brachial neuritis. Muscle Nerve 1994;17:320-4.

18. Ungley CC. Recurrent polyneuritis in pregnancy and the puerperium affecting three members of a family. J Neurol Psychopathology 1933;14:15-26.

19. Lederman RJ, Wilbourn AJ. Postpartum neuralgic amyotrophy. Neurology 1996;47:1213-19

20. Sierra A, Prat J, Bas J, et al. Blood lymphocytes are sensitized to brachial plexus nerves in patients with neuralgic amyotrophy. Acta Neurol Scand 1991;83:183-6.

21. Vriesendorp FJ, Dmytrenko GS, Dietrich T, Koski CL. Anti- peripheral nerve myelin antibodies and terminal activation products of complement in serum of patients with acute brachial plexus neuropathy. Arch Neurol 1993;50:1301-3

22. England JD. The variations of neuralgic amyotrophy. Muscle Nerve 1999;22:435-6.

23. Kuhlenbaumer G, Hannibal MC, Nelis E. Mutations in SEPT9 cause hereditary neuralgic amyotrophy. Nat Genet 2005;37:1044-6.

24. Sudo K, Ito H, Iwamoto I, et al. SEPT9 sequence alternations causing hereditary neuralgic amyotrophy are associated with altered interactions with SEP4/SEPT11 and resistance to Rho/Rhotekin- signalmg. Hum Mutat 2007;28:1005-13.

25. Vanermen B, Aertgeerts M, Hoogmartens M, Fabry G. The syndrome of Parsonage and Turner discussion of clinical features with a review of 8 cases. Acta Orthop Belg 1991;57:414-19

26. Rubin DI. Neuralgic amyotrophy clinical features and diagnostic evaluation. Neurologist 2001;7:350-6.

27. Dillin L, Hoaglund FT, Scheck M. Brachial neuritis. J Bone Joint Surg [Am] 1985;67-A:878-90.

28. Waxman SG. The flexion-adduction sign in neuralgic amyotrophy. Neurology 1979;29:301-4.

29. Schott GD. A chronic and painless form of idiopathic brachial plexus neuropathy. J Neurol Neurosurg Psychiatry 1983;46:555-7

30. Kilon LG, Nevin S. Isolated neuritis of the anterior interosseous nerve. Br Med J 1952;1:850-1.

31. Rennels GD, Ochoa J. Neuralgic amyotrophy manifesting as anterior interosseous nerve palsy. Muscle Nerve 1980;3:160-4.

32. Lahrmann H, Grisold W, Authier FJ, Zifko UA. Neuralgic amyotrophy with phrenic nerve involvement. Muscle Nerve 1999;22:437- 42.

33. Tsao BE, Ostrovskiy DA, Wilbourn AJ, Shields RW Jr. Phrenic neuropathy dug to neuralgic amyotropby. Neurology 2006;66:1582-4.

34. Dinsmore WW, Irvine AK, Callender ME. Recurrent neuralgic amyotraphy with vagus and phrenic nerve involvement. Clin Neurol Neurosurg 1985;87;39-40.

35. Chen YM, Hu GC, Cheng SJ. Bilateral neuralgic amyotrophy presenting with left vocal cord and phrenic nerve paralysis. J Formos Med Assoc 2007;106:680-4.

36. To WC, Traquina DN. Neuralgic amyotrophy presenting with bilateral vocal cord paralysis in a child: a case report. Int J Pediatr Otorhinolaryngol 1999;48:251-4.

37. Pierre PA, Laterre CE, Van den Bergh PY. Neuralgic amyotrophy with involvement of cranial nerves IX, X, XI, XII. Muscle Nerve 1990;13:704-7.

38. Seror P. Isolated sensory manifestations in neuralgic amyotrophy: report of eight cases. Muscle Nerve 2004;29:134-8.

39. van Alfen N, van Engelen BG, Reinders JW, Kremer H, Gabreels FJ. The natural history of hereditary neuralgic amyotrophy in the Dutch population: two distinct types? Brain 2000;123:718-23.

40. Airaksinen EM, Livanainen M, Karli P, Sainio K, Haltia M. Hereditary recurrent brachial plexus neuropathy with dysmorphic features. Acta Neurol Scand 1985;71.309-16.

41. Jeannet PY, Watts GD, Bird TD, Chance PF. Craniofacial and cutaneous findings expand the phenotype of hereditary neuralgic amyotraphy. Neurology 2001;57:19638.

42. Uetani M, Hayashi K, Matsunaga N, Imamura K, Ito N. Denervated skeletal muscle: MR imaging, work in progress. Radiology 1993;189:511-15.

43. Fleckenstein JL, Watumull O, Conner KE, et al. Denervated human skeletal muscle: MR imaging evaluation. Radiology 1993;187:213- 18.

44. West GA, Haynor DR, Goodkin R, et al. Magnetic resonance imaging signal changes in denervated muscles after peripheral nerve injury. Neurosurgery 1994;35:1077-85 45. Sallomi D, Janzen DL Munk PL, Connell DG, Tirman PF. Muscle denervation patterns in upper limb nerve injuries: MR imaging findings and anatomic basis. AJR Am J Roentgenol 1998;171:779-84

46. Helms CA, Martinez S, Speer KP. Acute brachial neuritis (Parsonage-Turner syndrome). MR imaging: report of three cases. Radiology 1998;207:255-9.

47. Scalf RE. Wenger DE, Frick MA, Mandrokar JN, Adkins MC. MRI findings of 26 patients with Parsonage-Turner syndrome. AJR Am J Roenigenol 2007;189-39-44.

48. Duman I, Givenc I, Kalyon TA. Neuralgic amyotrophy, diagnosed with magnetic resonance neurography in acute stage: a case report and review of the literature. Neurologist 2007;13:219-21.

49. Sankaya S, Sumer M, Ozdolap S, Erdem CZ. Magnetic resonance neurography diagnosed brachial plexitis: a case report Arch Phys Med Rehabil 2005;86:1058-9

50. Lo YL, Mills KR. Motor rooi conduction in neuralgic amyotrophy: evidence of proximal conduction block. J Neural Neurosurg Psychiatry 1999;66:586-90

51. Watson BV, Nicolle MW, Brown JD. Conduction block in neuralgic amyotrophy. Muscle Nerve 2001;24:559-63.

52. Bradley WG, Madrid R, Thrush DC, Campbell MJ. Recurrent brachial plexus neuropathy. Brain 1975;98:381-98.

53. Walsh NE, Dumitru D, Kalantri A, Roman AM Jr. Brachial neuritis involving the bilateral phrenic nerves. Arch Phys Med Rehabil 1987;68:46-8.

54. Aymond JK, Goldner JL, Hardaker WT Jr. Neuralgic amyotrophy Orthop Rev 1989;18:1275-9.

55. Tonali P, Uncini A, Di Pasqua PG. So-called neuralgic amyotrophy. clinical features and long term follow-up. Ital J Neurol Sci 1983;4:431-7.

56. Geertzen JH, Groothoff JW, Nicolai JP, Rietman JS. Brachial plexus neuropathy: a long-term outcome study. J Hand Surgery [Br] 2000;25:4610-4.

S. Sathasivam,

B. Lecky,

R. Manohar,

A. Selvan

From The Walton

Centre for Neurology

and Neurosurgery,

Liverpool, England

* S. Sathasivarn, MRCP(UK),

PhD, Consultant Neurologist

* B. Lecky, MD, FRCP,

Consultant Neurologist

Department of Neurology

* R. Manohar, MRCP(UK),

Specialist Registrar in

Neurophysiologv

* A. Selvan, DM, MRCP(UK),

Consultant Neurophysiologist

Department of

Neurophysiologv

The Wallon Centre for

Neurology and Neurosurgery,

Lower Lane, Liverpool L9 7LJ,

UK.

Correspondence should be sent to Mr S. Sathasivam; e-mail: sivakumar.sathasivam@ thewaltoncentre.nhs.uk

(c)2008 British Editorial Societv of Bone and Joint Surgery

doi:10.1302/0301-620X.90B5. 20411 $2.00

J Bone Joint Surg [Br] 2008;90-B;550-3.

Copyright British Editorial Society of Bone & Joint Surgery May 2008

(c) 2008 Journal of Bone and Joint Surgery; British volume. Provided by ProQuest Information and Learning. All rights Reserved.