We read with interest the article by Kang et al.1 about a 63-year-old male with a history of arterial hypertension and hyperlipidemia who developed SARS-CoV-2 vaccination associated plexopathy of the right upper limb (Parsonage Turner syndrome [PTS]), clinically exclusively involving the right phrenic nerve. Treatment with analgesics reduced pain, but right diaphragmatic weakness persisted until the last follow up, 8 months after onset.1 The study is stimulating but raises concerns that should be discussed.

We disagree with the diagnosis of PTS. Because the phrenic nerve originates from the cervical roots C3-5 without merging with other nerve branches of the brachial plexus, paralysis of the right diaphragm may result from radiculopathy or radiculitis of the C3-5 roots rather than plexitis. Another argument against the plexopathy is that there was no muscle weakness in the muscles innervated by nerves emanating from the right brachial plexus. A reduction in the compound muscle action potential (CMAP) when the axial nerve or the musculo-cutaneous nerve is stimulated could also be due to radiculopathy. There was also no sensory deficit in a distribution suggestive of plexopathy.

We also disagree with the statement that differential diagnoses of a SARS-CoV-2 vaccination associated PTS are sufficiently excluded. MRI of the cervical spine to rule out vertebral stenosis, spinal infarction, spondylosis, spondylarthritis, or herniated disc is missing. It is not mentioned whether F-wave studies of the ulnar, radial, median, and axillar nerves were performed. Needle electromyography (EMG) of muscles innervated by plexus branches is absent. Since plexitis has also been reported in connection with SARS-CoV- infection,2 it is crucial to be informed about the result of the PCR test. We should also know the results of the virus panel and the results of cerebro-spinal fluid (CSF) tests to rule out polyradiculitis (Guillain Barre syndrome). Polyradiculitis is a known complication of SARS-CoV-2 vaccinations.3

Confirmation of the phrenic nerve lesion by nerve conduction studies (NCSs) of the right phrenic nerve is lacking. Compound muscle action potential (CMAP) latency and amplitude upon phrenic nerve stimulation at the collum and recoding from the diaphragm may show prolonged distal latency and reduced CMAP.4 We should know if needle EMG of the diaphragm was done, which can show chronic denervation in case of a phrenic nerve lesion. A radiculopathy of the phrenic nerve fibers was not excluded.

A limitation of the study is that electrophysiological studies only concerned the right side and not the contralateral side. This is crucial to document any side differences in exams and to confirm the right-sided lesion.

Another limitation is that pulmonary embolism (PE) was not ruled out.1 PE must be ruled out because it can be associated with unilateral elevation of the diaphragm5 and because thrombosis is a common complication of SARS-CoV-2 vaccinations.6 Elevated hemidiaphragm was reported in 14% of patients with PE.5 PE may even manifest with shoulder pain.7

An explanation for dyspnoea after the first vaccine dose was not given.1 There was no pneumonia and no elevation of the diaphragm on the X-ray shown in Fig. 1.1 We should know if Bickerstaff encephalitis (BBE), a subtype of Guillain Barre syndrome has been ruled out.

We disagree with the notion that PST is an idiopathic condition in every case. Most commonly, PTS is due to diabetes. Other causes of PTS include hereditary neuralgic amyotrophy due to a point mutation or duplication in the SEPT9 gene, viral infection, parasitic infection, surgery, or anesthesia.

Overall, the interesting study has limitations that challenge the results and their interpretation. Clarifying these weaknesses would strengthen the conclusions and could improve the study. Before attributing elevated hemidiaphragm to PTS and SARS-CoV-2 vaccination alternative mechanism need to be ruled out.

In upper brachial plexopathy, findings of the sensory studies are abnormalities in the lateral antebrachial cutaneous, median sensory (particularly to the thumb), and radial sensory (particularly to the thumb) nerves.2 Studies of the supracapsular, axillary, and musculocutaneous nerves may appear abnormal.2 Findings of needle electromyography (EMG) include abnormalities in the supraspinatus, infraspinatus, deltoid, biceps brachii, and brachioradialis muscles. In our case, sensory nerve conduction studies (NCS) showed a decreased amplitude of sensory nerve action potentials in the right lateral antebrachial cutaneous than in the left (right = 9.2 microV; left = 30.9 microV). Further, motor NCS showed the compound muscle action potential amplitudes in the right axillary and musculocutaneous nerves were approximately 30% lower than those in the left nerves. These study results supported the diagnosis of right upper brachial plexopathy.

Due to the patient’s shoulder pain, we also considered the possibility of radiculopathy, and needle EMG was performed. The study was compatible with right cervical radiculopathy in the C7-T1.

Phrenic nerve EMG was not conducted in our case. We diagnosed the diaphragmatic dysfunction based on the elevated hemidiaphgram on chest radiographs and abnormal ultrasound findings of the elevated diaphragm. Ultrasound is noninvasive and has both high sensitivity and specificity for detection of diaphragmatic dysfunction.3 As we have described in the report, the diaphragmatic excursion and diaphragm thickening fraction were significantly reduced in the case patient, fulfilling the ultrasonographic criteria of diaphragmatic dysfunction.45 Needle EMG can detect evidence of denervation and is the best method to differentiate between neuropathic and myopathic causes of diaphragm weakness.6 However, it is uncomfortable, and can be technically challenging to perform and interpret. Pneumothorax may occur as a complication due to the proximity of vital structures and the depth of the diaphragm.45 C3-5 roots radiculopathy or radiculitis, the potential differential diagnosis that Professor Finsterer pointed out, might have occurred together with brachial plexopathy in our patient, but it is difficult to differentiate them and we determined the patient's symptoms were more consistent with brachial plexopathy correlating with the clinical features.

He was negative for SARS-CoV-2 infection confirmed by a real-time PCR test. The possibility of pulmonary embolism was excluded from chest CT with contrast enhancement. The chest CT images were reconstructed with 2-mm section thickness, which in general allows detection of pulmonary embolism.78 Although very small subsegmental pulmonary embolism might have been missed, we believe it is unlikely that such a tiny embolism could have contributed to significant shoulder pain and diaphragmatic dysfunction.

Since Guillain-Barre syndrome is a known complication of SARS-CoV-2 vaccination,9 it is reasonable to consider its possibility. Guillain-Barre syndrome has several forms and its initial signs and symptoms are variable among patients.10 Phrenic nerve paralysis can develop in patients with Guillain-Barre syndrome. However, we thought unilateral involvement of limb and diaphragm in Guillain-Barre syndrome was not typical, thus, a cerebrospinal fluid study was not conducted. Further, the patient did not have signs or symptoms suggestive of Bickerstaff brainstem encephalitis, such as ataxia, ophthalmoplegia, change in consciousness, or dysarthria.11

We appreciate your feedback that every neuralgic amyotrophy is not idiopathic. As you mentioned, infectious or immune triggers, and/or individual (genetic) susceptibility are assumed to be the cause of neuralgic amyotrophy. More importantly, we agree that efforts should be made to rule out all other possibilities before making the diagnosis of neuralgic amyotrophy.