Introduction

Parsonage-Turner Syndrome (PTS), also known as neuralgic amyotrophy, is an inflammatory nerve disease. It gets its name from the physicians M.J. Parsonage and J.W.A. Turner, who described the disease after examining it in a larger population group of 136 patients for the first time since its initial discovery in 1897.¹ The inflammation affects a network of nerves known as the brachial plexus, located in the shoulder blade and collarbone area between the neck and shoulder, or the “shoulder-girdle”. This manifests as sudden severe pain, weakness, numbness, and muscle wasting of the muscles in this area. In this article, we will go through the nature of the disease and the treatments that can be used in managing the disease, particularly immunotherapy and the considerations associated with it.

Pathophysiology

Motor and sensory nerves branching off the brachial plexus become damaged after being targeted by the body’s inflammatory response. This can present as swelling, hourglass-shaped constrictions of isolated nerves, or weak parts of the nerve that can be subject to further damage through movement.²

In hereditary PTS, the disease is caused by a gene mutation, specifically in the SEPT9 gene.^3,4 In idiopathic PTS, there is not a specific individual cause that has been identified, but it has been reported that most often it is triggered by a preceding event such as surgery, trauma, pregnancy or most commonly after infection or vaccination. Therefore, be an unprecedented side effect of certain treatments.^1,5,6 The theory stands that after such an event, the immune system can react by generating an undesirable inflammatory response, and the condition arises where those specific nerves are implicated. The affected muscles are the supraspinatus and infraspinatus muscles, which can be seen on an MRI.⁷

It can sometimes be difficult to diagnose, as there may be other culprits to the nerve damage that should be ruled out, aside from the immune-mediated inflammation, such as a cyst on the nerve, or complications that may have occurred during or after a surgery.⁶

This condition can cause significant disruptions to the lives of those it affects – a study showed that 25% of patients were still unable to work 3 years after the initial onset of the disease.⁸

Clinical spectrum

Let’s explore how the disease manifests in a bit more detail:

Phase 1 - It starts with an abrupt, intense shoulder pain that can radiate to the upper arm or neck, or in some cases, the lumbar region of the body, where these nerves are involved in 10% of cases.⁹ This lasts anywhere between a few hours to several days.¹⁰

Phase 2 - This is followed by weakness of the muscle, which makes it difficult to lift or move the arm on the affected side. This can also be accompanied by a loss of sensation and partial paralysis.

Phase 3 - The underuse of the muscle causes it to waste away (atrophy) gradually. This can be visible after a few weeks.^11,12

Over a matter of months to years, the disease is known to resolve, as the affected side regains power and feeling gradually restored, but for some, residual pain can persist chronically, leading to long-lasting disability in some cases.⁸ Recurrence occurs in 75% of hereditary PTS cases, in the first 5-10 years after onset.⁹

In children, the disease can be slightly different and is harder to diagnose, as verbal communication of symptoms is limited. Painless episodes of the disease seem to be a trend in the paediatric population, where their symptoms consist more of weakness and impaired functional movement.^3,9

Treating parsonage-turner syndrome

Having discerned that the disease is most likely immune-mediated, anti-inflammatory drugs that regulate the immune system’s response have been employed in treatment.

First line: Steroids

In people diagnosed with PTS, corticosteroids, an anti-inflammatory class of medications, are prescribed first line as early as possible. However, there are limitations to treatment with steroids, as symptoms can return when the steroid medication is weaned off.¹³ Considering that the condition is largely self-limiting, it could be difficult to discern whether recovery would have been the same after the natural course, as recovery times range between 1-3 years.²

Second line: Immunotherapy

The limitations of only painkillers and even steroids in treating the condition have led to immunotherapy being considered as a second-line alternative treatment, especially in severely persistent cases, where corticosteroids seem to be insufficient. Such options include infliximab for recurrent inflammatory attacks of the nerve.¹³

Adjunct treatment:

These main anti-inflammatory options are often initiated in combination with painkillers to address the initial painful phase, as well as any lasting pain. This has been proven by a few case studies to be effective in easing symptoms. Such as in a study using them alongside high-dose prednisolone, with reports of faster muscle strength recovery than those receiving non-steroidal anti-inflammatory (NSAID) medication. Surgical interventions have also yielded improvement in those who have persistent symptoms, where the nerve damage involves compression/impingement.^2,8

Rehabilitation:

This has been emphasised as one of the most important aspects of disease management to maximise disease recovery, especially where there is lasting muscle damage.^9,11

A closer look at immunotherapy in PTS

Intravenous immunoglobulins (IVIG) are the main immunotherapy type after steroids that have been experimentally tested in PTS. Immunoglobulins are antibody proteins from the blood, and they are accumulated from donors and administered into the blood of people needing the treatment. Its probable mechanism of action is complicated; it does not target any specific component of the immune system but instead involves dampening signals that may be directing the immune system to mark and attack the implicated nerves.

In the acute phase of PTS, it has been used to address pain in severe cases where analgesia is ineffective, and people who respond positively to IVIG treatment are almost pain-free a day or two after starting it. Where it has been tried, many have employed a combined treatment regimen together with corticosteroids to accelerate recovery, with evidence showing an initial recovery in as short as 5 months.⁶

In the chronic phase, 2 weeks after onset, IVIG treatment is not typically expected to have any effect. This is because the initial nerve damage itself is not necessarily to blame for persisting symptoms. Instead, these can be attributed to the decreased endurance in affected muscles, thus the subsequent strain and fatigue this causes in the surrounding muscles that need to overcompensate for the weak ones. The impaired positioning and altered posture can cause secondary nerve impingement over time.⁹ Despite this, there are reports of use in chronic cases, where IVIG has been given intermittently in a regimen known as “pulse therapy”, which has suggested a positive effect.¹⁴

Limitations

Although there is evidence to support its use, particularly in more severe cases, the research is not conclusive. The evidence is based on studies that are not very strong, with small population pools, control limitations, and variable diagnostic criteria. As with corticosteroid therapies, it is difficult to tell whether the recovery seen would have been any better than the condition’s natural course.¹⁴ One paper published in 2024 reports that there have only been 6 controlled cohort studies done on PTS treatment, and no randomised controlled trials.⁸ Therefore, employing immunotherapy in disease management is still experimental at best. Where it is used, though, time matters – with better prognosis reported when initiated in the early stages of the disease to shorten recovery time.³ Despite its proposed effectiveness, a full recovery is still no guarantee. Some degree of lasting injury is common, with many patients experiencing persistence of symptoms after initial functional recovery.^3,12

Summary

Immunotherapy is promising in aiding the recovery of Parsonage-Turner syndrome, which can be a very debilitating disease for many people. However, the limitations associated with using IVIG to treat PTS raise the question: Is it worth it? In a disease that is largely self-limiting with recovery times up to 1 year, the risk-benefit ratio of starting immunotherapy in the disease should be considered in each case. An integrated approach, involving physiotherapy alongside pharmaceutical management, including immune-modulating treatment, is proposed as the most viable treatment regimen. Going forward, more robust clinical trials are required to confirm efficacy, when in the disease immunotherapy could, or should, be used, and when to use them, just for the acute, or for the chronic phase too?