Increased ¹⁸ F-FDG uptake in denervated muscles in a case of Parsonage-Turner syndrome

The clinical and EMG/NCS findings of our patient suggests the diagnosis of PTS. However, other more common conditions that may cause acute shoulder pain and upper limb muscle weakness must be ruled out. Differential diagnoses include cervical radiculopathy, shoulder joint pathology, mononeuritis multiplex, multifocal motor neuropathy, and peripheral nerve entrapment. Other causes of brachial plexopathy such as trauma, post-radiation, primary or metastatic tumor, infection, vasculitis, and hereditary neuropathy with liability to pressure palsy should be ruled out. Blood examinations, imaging tests (High-resolution ultrasonography (HRUG), MRI, ¹⁸ F-FDG PET-CT) may assist in excluding conditions such as cervical disc pathology, and infectious or neoplastic etiologies. Initially, cervical radiculopathy was suspected in our case; however, MRI revealed minor disc protrusion between the cervical vertebral bodies of 4 and 5 (C4-5) and tiny marginal osteophytes that were more consistent with mild degenerative changes rather than C5 radiculopathy caused by acute cervical disc compression. Recent advanced studies in nerve imaging have shown focal abnormalities in proximal nerve segments of brachial plexus in 75–80% of PTS patients [1]. It is noted that MRN images of a proportion of PTS patients are normal, similar to the MRN of our patient. As a result of the clinical, imaging and EMG/NCS findings, we concluded that PTS seemed to be the most likely diagnosis [1, 2].

To rule out the possibility of malignant tumors and metastatic infiltration of the brachial plexus, ¹⁸ F-FDG PET-CT was performed on our patient. Although the MRN showed only suspected increased T2-weighted signal in left supraspinatus, it is interesting to note that on ¹⁸ F-FDG PET-CT imaging, affected muscles that experienced weakness (supraspinatus, deltoid and biceps muscles) showed a diffuse pattern of increased signal intensity. Increased radioactive uptake in tissues compared to baseline reflects an increase in glucose metabolism, which may indicate the presence of neoplasms, however, active inflammation and tissue repair could also be the cause. In a preliminary study, ¹⁸ F-FDG uptake was increased in denervated muscles 8-days post-nerve resection in rat models, which confirms glucose hypermetabolism in denervated muscles [6]. In another study conducted in rat models, glucose hypermetabolism began 2 days after nerve injury and lasted up to 12 weeks, with maximal increase at week 1 after denervation. ¹⁸ F-FDG signal intensity from the PET scans were strongly correlated with the severity of nerve injury. The mechanism for the increase in glucose metabolism after nerve injury is not fully understood; however, one of the postulated mechanisms is spontaneous muscle contraction after nerve injury. Molecular pathways that are thought to be involved, include the mammalian target of rapamycin (mTOR) and apoptosis pathway. In that study, the authors found increase in phosphorylated-mTOR and mTOR expression which peaked along with maximum 18 F-FDG uptake. Significant increased B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax)/Bcl-2 expression (ratio of apoptotic activity) was observed 7 days after denervation [7]. This suggests that the intensity of the increased 18 F-FDG uptake in the affected muscles of our patient may reflect the extent of nerve injury. Similar to our case, increased 18 F-FDG uptake in affected muscles in cases of brachial neuritis have also been reported [4, 5]. Although electrophysiological studies are considered the most important for the evaluation of peripheral nerve injuries, it usually takes time, up to 3 weeks after the initial insult of the nerve for EMG/NCS to display abnormalities. Similarly, the EMG of our case also only showed mild denervated changes in affected muscles 14 days after the onset of symptoms. As the literature has shown that PET imaging displays increased uptake in denervated muscles as early as 2–8 days after denervation, we proposed that PET imaging may detect muscle denervation earlier than EMG that typically does not show significant changes within 2 weeks following the onset of neuralgic amyotrophy. In the case of PTS, especially when initial EMG/NCV and MRN results are inconclusive, ¹⁸ F-FDG PET-CT may be useful in helping the early detection of muscle denervation, as in the case of PTS.

Although we did not perform HRUG in our patient, it is worth noting that HRUG can be a valuable tool in assessing PTS. Nerve swelling is the most common sonographic finding in PTS, other pathologic HRUS findings that are also observed in PTS include nerve constriction (incomplete or complete) and fascicular entwinement [8]. HRUG is readily available, lacks contraindications, and has shown good diagnostic utility when performed by experienced examiners. However, ultrasound imaging of the plexus itself can be challenging for non-specialized examiners due to limited accessibility beneath the clavicle. In such cases, MRN and 18 F-FDG PET-CT may be more sensitive in detecting muscle denervation.

The clinical features of our case are in concordance with most cases of PTS in literature [1]. The initial intense pain usually occurs prior to the onset of muscle weakness and does not correlate with the localization of the paresis [9]. In our case, there were no sensory symptoms associated with muscle weakness, which is reported in up to 78.4% of patients with suspected PTS [2]. In PTS, the most commonly affected nerves are the long thoracic and/or suprascapular nerve; however, any part of the brachial plexus can be involved [2]. Although most cases of PTS post-COVID-19 vaccination present with the classical form, atypical phenotypes of pure sensory or painless motor-predominant forms [10] and lumbosacral involvement [11] have also been observed. In our case, the time from the antecedent vaccination to the onset of PTS is 115 days, which is substantially longer than those of most cases [10‐24]; however, a recent case series reported cases that occurred 3 months after vaccination [20]. Although it is not feasible to establish a robust causal relationship between PTS and COVID-19 vaccination, but given that there were no other precipitating factors that could better explain for the clinical presentation of our previously healthy patient, the mRNA Moderna vaccine seems to be the most probable trigger. This observation suggests that the onset of PTS after a predisposing event could vary greatly from person to person, which may reflect the complex interplay between genetic predisposition and environmental factors as the etiologies of PTS.

In a large case series of 246 patients with PTS, most patients recovered from severe to mild residual muscle weakness in the course of months to a few years, with or without corticosteroid treatment. However, when comparing the corticosteroid-treatment patients with the untreated group, the duration of muscle weakness was significantly shorter [2]. In 2009, a Cochrane review suggested that administration of oral prednisolone during the first month of an attack could shorten the duration of pain and also accelerate recovery [3]. Similarly, administration of oral prednisolone to our patient when PTS was suspected led to substantially improved muscle weakness one month later. It is important to note that most cases of PTS post-COVID vaccination also reported the use of corticosteroids, which led to improvement in muscle weakness and near full recovery within the course of 1 to 6 months [10‐13, 15, 17‐24]. Our case report demonstrates that identification and accurate diagnosis of PTS is crucial because while debilitating, the prognosis of PTS is usually favorable if treated and managed promptly with treatments including corticosteroid medications and physiotherapy.