Introduction

Acute monophasic inflammatory neuropathy, Parsonage-Turner syndrome (PTS), usually manifests as abrupt, intense shoulder or arm discomfort, followed by atrophy, multifocal muscular weakness, and a variety of sensory abnormalities. Neuralgic amyotrophy was once thought to be uncommon, but more recent epidemiological and imaging research has revealed that it is more common and has a wider range of symptoms than previously thought. Additionally, many bouts are preceded by a systemic stressor, most frequently an infection. Early diagnosis, focused testing, prognosis, and possible immunomodulatory treatment all depend on the identification of viral triggers.¹ 

Epidemiology

A significant percentage of PTS attacks are temporally linked to antecedent illnesses, according to several observational series and case compilations. According to a recent systematic observational analysis, a significant minority of cases (roughly one-third to two-fifths in several series) had confirmed immune triggers, such as infections and vaccinations, prior to the onset of symptoms. This led the authors to recommend routine testing for intracellular pathogens when PTS presents acutely, especially in bilateral cases or when liver enzyme abnormalities are present. Causal inference begins with this epidemiological connection, which is seen across age groups and geographical locations.²

Case reports and studies have implicated a wide range of infectious agents, both viral and non-viral. There are several well-established correlations in the literature; the most frequently mentioned are the hepatitis E virus (HEV), parvovirus B19, SARS-CoV-2 (the virus that causes COVID-19), and a variety of other viral diseases that are described less frequently. The best-documented relationships are compiled here.

Hepatitis E virus (HEV)

Hepatitis E has emerged as one of the strongest infectious associations with PTS. Case series and focused reviews have documented numerous patients who developed bilateral or atypical neuralgic amyotrophy in temporal proximity to acute HEV infection, sometimes in the absence of pronounced hepatitis symptoms. Genotype 3 HEV, seen in industrialised countries and linked to zoonotic exposure, appears disproportionately represented in reported PTS cases. The HEV–PTS association is notable because it often presents with bilateral involvement and may be accompanied by liver enzyme derangement, prompting clinicians to check HEV serology or RNA in appropriate clinical contexts.³

B19 parvovirus

Numerous case studies have identified parvovirus B19, a tiny DNA virus that causes arthropathy in adults and erythema infectiosum in infants, as the most likely antecedent infection to PTS. According to these accounts, there is electrophysiological data that suggests brachial plexus or peripheral nerve involvement, followed by a characteristic painful beginning and localised weakening. Even while parvovirus-associated PTS seems uncommon, these case reports lend credence to the idea that a variety of viral infections can stimulate the immune system in vulnerable people.⁴

CoV-2 SARS (COVID-19)

Numerous case reports and systematic reviews have detailed PTS that happens soon after SARS-CoV-2 infection since 2020. PTS can occur following COVID-19 infection, according to a comprehensive analysis that compiled dozens of reported instances. It often manifests within days to a few weeks after infection and has typical clinical, electrophysiological, and imaging aspects. Both traditional upper-limb presentations and uncommon patterns (such as involvement of the phrenic nerve) are included in case series. Although the numbers are still small and susceptible to publication bias, data to date indicate a male predominance in reported COVID-related cases; yet, the uniform phenotype across reports and the temporal connection make SARS-CoV-2 a believable trigger.⁵

Additional infectious agents and viruses

Case reports have occasionally mentioned other pathogens, such as CMV, Epstein-Barr virus, human immunodeficiency virus, and several bacterial diseases. Absolute hazards associated with any one disease are still unknown since the case-level evidence, not big controlled research, predominates in the literature. However, the variety of implicated agents supports the idea that PTS is an immune-mediated, generic response to a variety of infectious stimuli in susceptible hosts.^1,2

Mechanism

• Post-infectious immunological dysregulation/molecular mimicry: The brachial plexus may be harmed by cross-reactive adaptive immune responses (antibody and T-cell driven) triggered by antigenic similarity between pathogen proteins and peripheral nerve antigens. Though PTS and Guillain-Barré syndrome (GBS) have different clinical and electrophysiological signs, this model is conceptually similar to GBS after Campylobacter or Zika virus infection^1,2
• Direct viral neurotropism: Direct nerve tissue infection may be a factor for certain viruses. The clinical picture and timing, however, more strongly support an immune-mediated process than a direct viral invasion, and viral RNA is not found in nerve tissue in the majority of PTS reports. For instance, compared to regular direct neuroinvasion, HEV and SARS-CoV-2 connections more closely resemble a para-infectious immunological trigger^3,5
• Hereditary brachial plexus neuropathy (HBPN) is caused by SEPT9 and other genetic variants in a subset of patients. These patients exhibit similar attacks following minor stressors, infections, or vaccinations, suggesting that genetic predisposition influences the risk and phenotype of immune-triggered attacks. Finding inherited forms demonstrates how infection can act as a direct trigger against a background of innate vulnerability^1,8
• Bystander inflammation and innate immune activation: Systemic infection causes innate immune cell activation and cytokine release, which may foster an environment that is favourable for localised immunological attacks on brachial plexus tissues. Although the reason behind the preference for particular nerve distributions is unknown, it could be related to local immunological microenvironments or microanatomic vulnerability^1,2

Diagnosis

Identification and evaluation

Clinicians should often inquire about recent feverish illnesses, specific exposures (e.g., undercooked pork or zoonotic exposures for HEV genotype 3), and recent SARS-CoV-2 infection or vaccination because infections are known antecedents in a significant minority of PTS cases. In the acute phase, focused testing for HEV, parvovirus B19, HIV, and other intracellular pathogens makes sense when clinical indicators point to an infectious relationship (e.g., abnormal liver enzymes, bilateral symptoms, or concurrent systemic characteristics). Given the diagnostic and occasionally therapeutic implications, a recent observational study specifically advised such testing.^2,3

Imaging and electrophysiology

MRI and MR neurography often show T2 hyperintensity and denervation changes in affected muscles and plexus structures; electrodiagnostic studies (needle electromyography and nerve conduction studies) often show axonal loss in multiple distributions corresponding to brachial plexus involvement. These techniques help confirm the diagnosis, ruling out structural reasons (such as compressive neuropathy), and recording the involvement distribution for prognosis and, if necessary, surgical planning. Denervation patterns in the supraspinatus/infraspinatus and other shoulder girdle muscles are frequently observed in imaging investigations conducted on PTS populations.⁷

Prognosis

The majority of PTS management is still supportive, with a focus on early physiotherapy, pain management, and rehabilitation. Many experts employ early corticosteroids and intravenous immunoglobulin (IVIG) in certain severe or prolonged attacks due to the involvement of an inflammatory immune system. Although there is insufficient data from randomised trials, case series, and small observational cohorts indicate that early immunomodulatory medication may shorten the duration of pain and may enhance functional recovery. In accordance with infectious illness recommendations, therapy should also address the underlying infection when a specific infectious trigger is recognised (e.g., acute HEV with active viremia). Therefore, knowledge of an infectious precipitant may alter diagnostic procedures and, in some cases, guide treatment.^1,3

Although chronic pain and lasting impairments are prevalent, many patients recover largely over months; cases involving bilateral or phrenic nerves may have worse outcomes. Although bilateral cases linked to viruses like HEV have been reported and warrant further investigation, the existence of a recognised infectious trigger does not always indicate a better or worse prognosis.^1,3

Summary

Parsonage-Turner syndrome (PTS) is now viewed as a more common, multifactorial illness in which infections are important precipitating factors, rather than a rare, idiopathic neuropathy, as a result of the amount of research gathered over the previous 20 years. An immune-mediated mechanism of disease is strongly supported by the continuous temporal correlation of infections like parvovirus B19, SARS-CoV-2, and hepatitis E virus with the onset of acute neuralgic amyotrophy episodes. These findings are consistent with the larger neurological paradigm, which holds that systemic infections act as triggers for immune attacks on the peripheral nervous system that are either post-infectious or para-infectious. These attacks are conceptually similar to Guillain-Barré syndrome but have different anatomical and clinical signs.

Identifying infection-related triggers has useful applications from a therapeutic standpoint. When a patient presents with abrupt shoulder discomfort and weakness, doctors should routinely ask about respiratory infections, gastrointestinal complaints, or previous feverish diseases. Targeted laboratory work-up for infections like HEV or parvovirus B19 may help confirm the diagnosis and direct treatment of the underlying infection in people with bilateral symptoms or abnormalities in biochemical liver tests. The case for early immunomodulatory treatments, such as intravenous immunoglobulin or corticosteroids, which have not yet been proven in randomised controlled trials but have shown potential in tiny series, can also be strengthened by knowledge of an infectious antecedent.

In summary, viruses and infections are not coincidental observations; rather, they are key factors in the development of Parsonage-Turner syndrome. They serve as triggers for an immune-mediated process that culminates in the brachial plexus, resulting in chronic morbidity, excruciating pain, and weakness. Researchers must use this information to better understand disease causes and enhance patient care, while clinicians must incorporate it into their diagnostic and treatment strategies. The neurology community must continue to be alert, cooperative, and creative in addressing this mysterious but better-understood disease as the post-infectious landscape changes, as demonstrated by the rise of COVID-19-related cases.