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SPECIAL SECTION on COVID-19 and PM'R

Extended Neuralgic Amyotrophy Syndrome in a Confirmed COVID-19 Patient After Intensive Care Unit and Inpatient Rehabilitation Stay

Alvarez, Armando MD, MPH; Amirianfar, Edwin DO; Mason, Marisa Carino BS; Huang, Laura MD; Jose, Jean MD; Tiu, Timothy MD

Author Information
American Journal of Physical Medicine & Rehabilitation: August 2021 - Volume 100 - Issue 8 - p 733-736
doi: 10.1097/PHM.0000000000001795

Abstract

Neuralgic amyotrophy (NA), otherwise known as Parsonage-Turner syndrome or brachial plexus neuritis, is a condition classically characterized by acute onset shoulder pain, lasting between 2 hrs and 8 wks, followed by patchy paresis in the upper limb and shoulder girdle. Commonly affected muscles include the spinati, serratus anterior, deltoid, biceps, and triceps. There are various other phenotypes, which include lumbosacral plexopathy, phrenic nerve palsy, lower cranial nerve involvement, and predominant sensory symptoms.1–3

The etiology of NA is often unknown but is commonly associated with a recent upper respiratory viral tract infection (i.e., herpes simplex virus, Borrelia burgdorferi, typhoid fever, coxsackievirus, parvovirus B19, cytomegalovirus, HIV, smallpox, and influenza). It is hypothesized that infection leads to an aberrant increase in the number of antibodies against peripheral nerve myelin, leading to inflammation. Rarely, NA is due to an autosomal dominant mutation in the septin protein family, a protein involved in glial cell cytoskeleton regulation and function.3 Overall, NA is a rare condition with a reported incidence of approximately 2–3 cases per 100,000, although underrecognition and misdiagnosis suggest the true annual incidence to be at least 20–30 cases per 100,000. Neuralgic amyotrophy is a clinical diagnosis, but magnetic resonance imaging (MRI) scans, electromyography (EMG), and nerve condition studies (NCSs) may help evaluate for other causes, such as cervical radiculopathy, peripheral nerve entrapment, or mononeuritis multiplex. Nerve condition studies and EMG can also help localize the lesion and provide information regarding the extent of nerve injury, as well as prognostication for recovery. Management of NA typically involves a multidisciplinary approach.3

Since the beginning of the COVID-19 pandemic, there has been a tireless effort to understand the pathophysiology, clinical presentation, and consequences of this catastrophic virus.4–7 Although there is robust evidence of respiratory complications after COVID-19, a growing number of case reports have identified neurological manifestations as both prodromal signs and complications of COVID-19.8 Since the first case of Guillain-Barre syndrome and COVID-19 was published by Zhao et al.9 in April 2020, the medical literature has sprouted with other neurological manifestations of COVID-19 involving the central and peripheral nervous system.9–17 Brachial plexopathy, optic and vestibular neuritis, and Guillain-Barre syndrome subtypes, such as acute motor axonal neuropathy, and Miller Fisher syndrome have also been reported.18–23

Both traumatic and atraumatic etiologies of COVID-19–related brachial plexopathy have been reported. Traumatic etiologies of brachial plexus lesions related to COVID-19 are thought to be secondary to traction or pressure during prone positioning, a technique used to bolster oxygenation.24 A case report by Mitry et al.25 and one retrospective case series by Miller et al.26 have identified NA as a potential complication of COVID-19 due to atraumatic mechanisms. In the scenario of atraumatic NA, it is postulated that the COVID-19 virus can act as a direct neuropathogen invading cells. Other possible mechanisms include nerve damage through direct cytotoxic effects or through molecular mimicry.27 The case presented adds to the growing evidence of neurological complications related to COVID-19. This study conforms to all CAse REport guidelines and reports the required information accordingly (see Supplemental Checklist, Supplemental Digital Content 1, http://links.lww.com/PHM/B308).

CASE DESCRIPTION

A 46-yr-old woman with a history of gastritis and anxiety presented to clinic as a follow-up after a hospital course for COVID-19. She initially presented to the emergency department and tested positive for COVID-19 using a polymerase chain reaction test after 4 days of progressively worsening shortness of breath and fatigue. She was discharged home from the emergency department with recommendations for supportive care and instructions to return to the emergency department if symptoms worsen. She later presented to the emergency department 4 days later with progressively worsening shortness of breath and admitted to the hospital. She was subsequently intubated 2 days after admission and remained intubated and mechanically ventilated for 23 days. During her intubation, she was in prone positioning intermittently. She had no medical history of respiratory or neurological diseases and had no family history of neurological diseases. Upon extubation and discharge from the acute inpatient hospital, her neuromuscular examination was noted to have pain and weakness in the left shoulder as documented by physical therapy notes 8 days after extubation. At that time, she was experiencing left upper limb weakness and pain with proximal weakness greater than distal and 3/5 strength in abduction of the left shoulder, shoulder flexion, and flexion of the left elbow. No previous documentation of left upper limb weakness was noted. Upon admission to inpatient rehabilitation, she had moderate assistance for upper body dressing and upon discharge was modified independent, although muscle manual testing remained the same.

Three weeks after discharge from inpatient rehabilitation, she was seen in clinic. Upon outpatient evaluation, she complained of left shoulder pain and weakness that began to become more pronounced for her after her discharge from inpatient rehabilitation. She described left shoulder pain, weakness, and numbness that started in the deltoid region and radiated to her elbow. She also endorsed left lateral thigh and bilateral medial thigh numbness, with weakness in the left lower limb.

On physical examination, she had a positive sulcus sign, atrophy of the left shoulder, and tenderness of the subacromial region. Active range of motion was limited because of pain but intact passively. Left shoulder abduction and extension were both 4/5 in motor strength. Hawkins and empty can tests were positive on the left. Hoffman reflex was elicited on the left. Left hip flexion strength was 4/5 with diminished sensation to crude touch in the left lateral thigh. Unless otherwise stated, all other strengths, reflexes, and sensation were intact in the bilateral upper and lower limbs.

Magnetic resonance imaging of the brain was normal. Magnetic resonance imaging of the left shoulder showed moderate tendinosis of the subscapularis, supraspinatus, and infraspinatus and the long head of the biceps tendon, with low-grade tenosynovitis within the bicipital groove. Moderate edema of the deltoid, teres major, teres minor, and the latissimus was suggestive of brachial plexopathy as shown in Figure 1.

FIGURE 1
FIGURE 1:
Sagittal (A) and coronal oblique (B) proton density fat-suppressed images, as well as sagittal (C) and coronal oblique (D) T1-weighted images, of the left shoulder, demonstrate denervation edema (arrows), fatty infiltration (curved arrows), and mild atrophy of the deltoid, teres minor, teres major, and latissimus dorsi muscle bellies, reflecting multinerve distribution brachial neuropathy/plexopathy.

Given these findings, NCSs/EMG and MRIs of the brachial plexus, thoracic spine, and cervical spine were obtained over the next 2 mos. The NCS/EMG findings included a mild left median neuropathy at the wrist and motor unit recruitment pattern consistent with a chronic left upper trunk plexopathy with reinnervation as shown in Table 1. Magnetic resonance imaging of the cervical, brachial plexus, and thoracic spine were unremarkable. Of note, the previous muscle edema of periscapular muscles had resolved.

TABLE 1 - Needle EMG of the left upper limb revealed increased insertional activity of the left biceps, increased insertional activity of the left infraspinatus, polyphasic motor units in the pronator teres, and increased insertional activity of the left deltoid with increased duration and polyphasic motor units with reduced motor unit recruitment pattern
Side Muscle Nerve Root Ins Act Fibs PSW AMP Duration Poly Recruitment Int Pat
Left 1stDorInt Ulnar C8-T1 Nml Nml Nml Nml Nml 0 Nml Nml
Left PronatorTeres Median C6-7 Nml Nml Nml Nml Nml 1+ Nml Nml
Left Biceps Musculocut C5-6 Incr Nml Nml Nml Nml 0 Nml Nml
Left Deltoid Axillary C5-6 Incr Nml Nml Nml >12 ms 3+ Reduced 75%
Left Cervical parasp mid Rami C4-6 Nml Nml Nml
Left Infraspinatus SupraScap C5-6 Incr Nml Nml Nml Nml 0 Nml Nml
Left ExtCarRadBrev Radial C6-7 Nml Nml Nml Nml Nml 0 Nml Nml
The remaining muscles, first dorsal interosseous, extensor carpi radialis brevis, and the midlevel cervical paraspinals demonstrated no abnormal spontaneous activity and normal motor unit recruitment patterns.
Ins Act, insertional activity; Fibs, fibrillations; PSW, positive sharp waves; AMP, amplitude; Int Pat, interference pattern.

The patient was being managed conservatively with meloxicam on an as-needed basis, and her symptoms resolved over the course of approximately 3 mos. At this time, the patient was diagnosed with extended NA syndrome. On follow-up examination, her strength and Hoffman sign had normalized.

DISCUSSION

As the incidence and prevalence of COVID-19 infection continue to grow, care providers need to be aware of the unique sequelae of the disease process and related treatment modalities. This report describes a unique presentation and case of COVID-19 and the NA subtype known as extended NA syndrome.

Extended NA syndrome is a subtype of NA that can affect both the brachial plexus and nerves outside of the brachial plexus, such as the lumbosacral plexus, phrenic nerve, or recurrent laryngeal nerve.3 The patient presented previously was found to have multiple physical examination findings suggestive of lumbar plexopathy, including decreased left hip flexion strength and diminished sensation on the left lateral thigh. Her left shoulder MRI also revealed signs of muscle denervation and muscle edema in the subacute phase after COVID-19 infection, supporting neuropathy related to NA.1,3,27 The Guillain-Barre syndrome and other Guillain-Barre syndrome subtypes were less likely, as she had no signs of acute ascending paralysis, ophthalmoplegia, or other cranial nerve weakness, gait ataxia, or areflexia.

There are multiple reports of brachial plexopathies related to COVID-19, most of which are associated with a traumatic mechanism, such as prone positioning, traction, or pressure.24,26,28 However, a focal traumatic etiology cannot explain involvement of nerves outside of the brachial plexus. Therefore, it is more plausible that this patient’s case of COVID-19–associated extended NA syndrome is more likely from an atraumatic mechanism of which at least three immune mediated etiologies have been postulated. The first is direct neuropathogenicity in which the virus directly invades the peripheral nerves via the angiotensin-converting enzyme 2 receptor. Secondly, in molecular mimicry, antibodies against viral surface glycoproteins target similarly structured glycoconjugates in human nervous tissue. The third is through direct cytotoxic effects on peripheral nerves.27 Moreover, COVID-19 has also been reported to affect purely sensory nerves. As described by Cacciavillani et al.,29 a patient reported sensory disturbances along the distribution of the lateral antebrachial cutaneous with NCSs showing a drop in the sensory action potential amplitude of the lateral antebrachial cutaneous.

Since the time this article was written in April 2021, the United States is tallying nearly 31 million cases of COVID-19 infection and more than 560,000 related deaths.30 In just 1 yr, COVID-19 has become the third greatest cause of mortality in the United States for those aged 45–84 yrs and the second leading cause of death for persons older than 85 yrs.31 Vaccinations are slowly catching up with nearly 229 million vaccines administered since the writing of this article.30 Although still early in the process of vaccination, early models predict a decrease in the number of intensive care hospitalizations and deaths.32 Nevertheless, physicians should begin to prepare themselves for the anticipated shift in health care toward treating the long-term complications of COVID-19. It is paramount that the physicians of today and tomorrow remain vigilant of multisystem sequelae and their potential atypical presentations.

CONCLUSIONS

The case described previously provides additional knowledge to the growing data of COVID-19 and its unique manifestations upon the neurological and musculoskeletal system. Moreover, our case provides objective data using physical examination showing weakness and sensory abnormalities confirmed and correlated with findings from EMG, NCSs, and MRI.

As more information and research continues to be provided for COVID-19, clinicians must continue to be cognizant of the vast array of long-term complications the virus may have on patients. As the previously mentioned case demonstrates, varying neurological and musculoskeletal presentations may become more common. Continued research and follow-up of patient’s afflicted by COVID-19 may reveal more variant manifestations.

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Keywords:

COVID-19; Neuralgic Amyotrophy; Parsonage-Turner Syndrome; Brachial Plexus Neuritis

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