Neuralgic Amyotrophy

Definition

Nerualgic Amyotrophy (NA), also called idiopathic brachial plexus neuropathy or Parsonage-Turner-Syndrome, is a multifactorial disease with sudden onset, which presents itself with intense pain and paresis of the innervation territory of the brachial plexus.

Aetiology

As NA is a relatively complex disease and therefore the precise pathophysiology has yet been discovered. Regarding the different mechanisms of disease, NA can be divided into two different categories: Hereditary NA (HNA) and idiopathic NA (INA). Alterations on chromosome 17q25, which code for the Septin-9 protein (SEPT9) are responsible for developing HNA. However it is not inherited according to classical genetics and therefore has a penetrance of 80%-90% [1]. Altered versions of the protein bind and bundle microtubules [3].

The most likely mechanism that is discussed is autoimmune triggers, which were found in 50% of patients preceding the symptomatology of NA. These triggers were mostly infections (Hepatitis E, Coxsackie A2 etc.), surgeries, childbirth and physical or mental stress [2].

Biomechanical strain is another factor associated with NA. In up to 10% of NA cases, physically demanding and/or unusual exercise of the upper extremity precedes an attack of neuralgic amyotrophy [1]. It is explained that the mechanical exhaustion leads to an inflammation of the nerves resulting in a loosening of the blood-nerve-barrier.

Epidemiology

The overall incidence amounts to 1/1000/year with men being affected twice as much as women. The median onset age is estimated at 40 years for INA and 25 years for HNA [1] as patients from 3 to 80 years of age are affected [3]. INA is reported to be 10 times more common than its hereditary counterpart [4]. In 97% of cases the pathology occurs asymmetric and involves the right upper limb twice as much compared to the left upper limb [3].

History

The examiner should pay close attention to the patient’s history since it can provide first indications of neuralgic amyotrophy. Sudden onset pain with signs of paresis in the shoulder within hours or days later should always suggest need for further explanation.

Disease specific diagnosis

First of all, neuralgic amyotrophy is a primarily clinical diagnosis. It can be, however, accompanied by laboratory testing, EMG and imaging diagnostics.

For a clinical diagnosis, the examiner inspects and palpates the upper extremities as well as the shoulder blade for any asymmetry in strength or muscle atrophy. With special regards to scapular dyskinesia, deficits in shoulder abduction and anteflexion, weakness in serratus anterior, external rotation, long thumb and index finger flexors or forearm pronation the examiner may suspect a diagnosis of neuralgic amyotrophy. Additionally, there are other signs of NA such as atrophy of the brachialis muscle and irregular breathing patterns, which aggravate in supine position [1].

Routine blood-tests are always non-conclusive, but laboratory testing can be used to rule out other similar diseases, such as pressure palsies etc., in vague cases with relatively low pain-levels [1].

To confirm the diagnosis, an electromyography (EMG) can be performed. The EMG may show signs of denervation and/or reinnervation but should never be fully trusted as there is a high chance of receiving negative results due to sampling error (muscles involved in NA are often not routinely examined in EMG) [1]. In other words, a negative EMG does not exclude NA.

Imaging technologies such as magnetic resonance imaging or ultrasound have not been established as the most reliable diagnostic tool yet, as most of the visible alterations are transient and might not be discovered at certain points in time. Affected nerves show hour-glass-like constrictions as well as swelling of the perineurium, which in combination with the possibility to exclude differential diagnosis and preoperative planning should still make MRI and US valuable diagnostic tools [2]. Case examples can be found on Radiopaedia.

Differential Diagnosis

• Musculoskeletal shoulder pain / Myofascial shoulder pain

  • • Gradual increase in pain, limited passive range of motion

• Cervical radiculopathy

  • • Symptoms only fit territory of one cervical root

• Traumatic nerve lesion

  • • Distinct event in the past

• Nerve compression

  • • Fascicular compression without signs of external nerve compression

• Hereditary neuropathy with liability to pressure palsy (HNPP)

  • • painless

• Transverse myelitis

  • • Often bilateral and MRI shows spinal cord affection

25% of patients with idiopathic NA and 75% of patients with hereditary NA experience a second or more attacks during the first few years after the first attack. New attacks might affect the same limb but can also affect different parts of the body or the same limb with different patterns [1]. Also, subsequent attacks generally occur with less severe symptoms [4]. Patients with hereditary NA are plagued by a less favourable outcome as they have earlier attacks, more frequent recurrence, more extra-brachial attacks, longer duration of pain and suffer more frequently from lasting disability due to multiple attacks [3].

Several prognostic factors have been identified [4]:

Good prognosis:

• Predominantly upper trunk involvement

• Primarily sensory symptoms

Poor prognosis:

• Prolonged pain

• Prolonged weakness

Overall, it can be said that prognosis does not look favourable. Two years after the initial onset, 25% to 33% of patients still suffer from intense pain and over 50% face challenges due to NA in their everyday life. Only about 4% of patients recover completely from neuralgic amyotrophy [1].