key: cord-0943545-urt66g17
authors: Hameed, Sajid; Farooq, Ayisha; Khan, Sara
title: Electrodiagnostic findings in COVID-19 patients: A single center experience
date: 2021-10-13
journal: Clin Neurophysiol
DOI: 10.1016/j.clinph.2021.10.001
sha: c5fee665c41f078eaacff78fcd3a03d0977158db
doc_id: 943545
cord_uid: urt66g17

OBJECTIVE: Neurological manifestations in patients with coronavirus disease 2019 (COVID-19) have been reported from early features of anosmia and dysgeusia to widespread involvement of the central nervous system, peripheral nervous system, as well as the neuromuscular junction and muscle. Our study objective is to evaluate the electromyography and nerve conduction study (EMG/NCS) findings among COVID-19 patients and look for possible correlations. METHODS: This is a hospital-based retrospective observational study. All COVID-19 patients between the period of 1st January 2020 to 31st December 2020 undergoing an EMG/NCS were included. RESULTS: Eighteen patients (12 male and 6 female) were included. Mean age was 55 ±12 years. 11 patients required intubation for a mean period of 18.6 days (range: 3-37 days). Electrodiagnostic findings were consistent with a myopathy in a majority of these patients (82%). Five of them also had a concurrent axonal neuropathy. In the remaining patients who did not require intubation (n=7), three patients had myopathic EMG changes and one had Guillain Barre syndrome. CONCLUSION: At this time, there are no neuromuscular-specific recommendations for patients who contract COVID-19. Only time and additional data will unveil the varying nature and potential neurological sequelae of COVID-19. SIGNIFICANCE: Myopathic EMG changes are commonly seen in critically ill COVID-19 patients, especially with a prolonged hospital stay. Abbrevations AIDP, Acute idiopathic demyelinating polyneuropathy; AMAN, Acute motor axonal neuropathy; AMSAN, Acute motor sensory axonal neuropathy; CIM, Critical Illness myopathy; CIN, Critical illness neuropathy; CK, Creatine Kinase; CNS, Central nervous system; COVID-19, Coronavirus disease 2019; EMG, Electromyography; GBS , Guillain Barre syndrome; NCS, Nerve conduction study; PNS, Peripheral nervous system; SNAP, Sensory nerve action potential

The coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome (SARS) caused by the SARS-CoV-2 coronavirus. More than 209 million confirmed cases and over 4.4 million deaths have been reported worldwide, as of August 20, 2021 (Johns Hopkins University Coronavirus Resource Center, 2021 . Neurological manifestations in COVID-19 have been reported from early features of anosmia and dysgeusia to widespread involvement of the central nervous system (CNS), peripheral nervous system (PNS), as well as the neuromuscular junction and muscle (Román et al., 2020) . Different neuromuscular manifestations have been reported in COVID-19 patients with myalgia being the most common symptom (Paliwal et al., 2020) .

Critical illness myopathy (CIM) has been frequently seen in patients with severe COVID-19 disease with a prolonged hospital stay (Cabañes-Martínez et al., 2020) . Our study objective is to evaluate the electromyography and nerve conduction study (EMG/NCS) findings among COVID-19 patients presenting to our neurophysiology laboratory and look for possible correlations.

This is a hospital-based retrospective observational study. All COVID-19 patients between the period of 1st January 2020 to 31st December 2020 referred to the neurophysiology laboratory at the Aga Khan University Hospital Karachi, Pakistan for an EMG/NCS were eligible to be included in this study. EMG/NCS was ordered by the primary intensive care physician or a neurologist taking part in the clinical care of patients. Inclusion criteria included > 18 years of age and a COVID-19 infection confirmed by a reverse transcriptase-polymerase chain reaction (RT-PCR) assay of a nasopharyngeal swab sample. Patients with pre-existing neuromuscular disorders were excluded. This study was approved by the Ethical Review Committee of the AKUH (Ref: 2020-5469) and the informed consent requirement was waived.

The electrodiagnostic study consisted of motor and sensory nerve conduction studies followed by concentric needle electromyography examination. Sensory NCS were conducted with antidromic stimulation. All studies were performed using a Nicolet Viking machine. Low-and high-pass filters were set at 2 kHz and 20 kHz, and 20 Hz and 2000 Hz for motor studies and sensory studies, respectively, with a sweep speed of 2 ms/division. The stimulus duration was of 0.05 or 0.1msec, as needed. The acceptable limb temperature for performing NCS was ≥32°C. In the event of low limb temperatures, the patients were warmed up using a heating pad or hot water bags to maintain the required temperature, as needed.

NCS: We studied motor and sensory NCS as per the protocol. In all patients, the nerves of the upper (median) and lower extremities (sural, peroneal, and posterior tibial nerves) were examined. In cases of peripheral neuropathy, a superficial peroneal or medial and lateral plantar nerves are additionally examined depending upon whether sural nerve was absent or present, respectively, in the lower extremities. Ulnar and/or radial nerves were also additionally performed in upper extremities in the peripheral neuropathy protocol. EMG: Needle electrode examination was performed using disposable concentric needles. The number of muscles examined was determined by the patient's clinical history and electrodiagnostic findings, however, at least seven muscles in the upper extremities and six muscles in the lower extremities (both distal and proximal muscles) were examined in every patient. Amplitude and duration of motor unit action potentials (MUAPs) along with polyphasic potentials and recruitment pattern were evaluated, in addition to the presence or absence of spontaneous activity.

Myopathy: Myopathy is defined on the basis of NCS/EMG findings. The EMG findings of short motor unit action potentials, with decreased amplitude and duration, along with normal sensory and motor NCS were seen. However in some of the patients, low compound muscle action potentials were also noted. 

Eighteen patients (12 male and 6 female) were included in our study (review Table 1 and 2 for details). The mean age was 55 +12 years. A total of 2,426 adult patients (> 18 years) had a diagnosis of COVID-19 patients either at the time of admission or during the course of the hospital stay during the study period. Our study subjects had multiple comorbidities, with the most common comorbid condition being hypertension (67%, n=12), followed by diabetes mellitus (50%, n=9) and asthma (22%, n=4). The mean duration from the diagnosis of COVID-19 infection to the performance of the electrodiagnostic study was variable, ranging between 4 to 180 days, with a mean duration of 41 days.

Eleven patients suffered from severe COVID-19 infection and required intubation for a mean period of 18.6 days (range: 3-37 days). Indication for EMG/NCS in these intubated patients was either a difficulty to wean off the ventilator support or development of flaccid quadriparesis.

Electrodiagnostic findings were consistent with a myopathy in a majority of these patients (82%, n=9). Five of them also had a concurrent axonal neuropathy. In 4 out of 9 patients with myopathic EMG changes (44%), spontaneous activity consisting of fibrillations and positive sharp waves were seen. Mean peak creatine kinase (CK) value was 246 IU/L (range: 66-876 IU/L). Unfortunately, muscle biopsy was not performed in any of the patients, which is one of the major limitations of our study. One patient had chronic peripheral neuropathy without myopathic EMG changes, and one had an acute motor and sensory axonal neuropathy (AMSAN) variant of GBS. Understandably, these patients had multiple comorbidities and had poor outcome with a 46% mortality. All of the intubated patients received systemic steroids (100%) and half of them also received tocilizumab.

In the remaining patients who did not require intubation (n=7), three patients had myopathic EMG changes (irritable in 1), one patient each had GBS (AMAN variant), bilateral common peroneal mononeuropathies, bilateral ulnar mononeuropathies along with bilateral carpal tunnel syndrome (CTS), and an active on chronic intraspinal canal lesion affecting L2 and L5-S1 myotomes. Interestingly, none of these patients had a large-fiber peripheral neuropathy. Mean peak CK value for patients with myopathic EMG changes was 64 IU/L (range: 28-93 IU/L). Half of the non-intubated patients received steroids and two patients (29%) also received tocilizumab.

No mortality was seen in this non-intubated patient group.

Neurological manifestations in COVID-19 occur in one-third of all COVID-19 infections (Mao et al., 2020) . A drastic increase of critical illness myopathy (CIM) has been observed in COVID-19 survivors who have been exposed to long-term mechanical ventilation. The underlying mechanism is not well understood and may involve the release of factors affecting muscle secondary to immobilization (Lönnqvist et al., 2020) . It is also proposed that cytokine release causes inactivation of sodium channels, thereby causing a slowing of muscle fiber conduction velocity and a simultaneous increase in calcium permeability that leads to myonecrosis Growing evidence suggests that neuromuscular manifestations like GBS, rhabdomyolysis, and neuralgic amyotrophy are also on the rise (Guidon and Amato, 2020; Pergolizzi Jr et al., 2020).

In another systemic review, AIDP was reported to be the most common variant of GBS in COVID-19 patients (De Sanctis et al., 2020) . There are also reports of the Miller Fischer variant of GBS being associated with COVID (Senel et al., 2020; Ray, 2020; Lantos et al., 2020) .

Interestingly in our study, two patients who were diagnosed with GBS either had the AMAN and AMSAN variant, respectively. The pathogenesis of GBS in COVID-19 is still unclear. Whether COVID-19 produces antibodies against specific gangliosides still needs to be determined. Ideally, longitudinal studies should undertake careful neurological imaging and electrophysiological examinations to understand the congruent interplay between COVID-19 induced myopathy and CIM. This can be followed by adequate access to rehabilitation facilities in patients who require rehabilitative services even after the resolution of infection.

Lack of muscle biopsy and a small number of patients were the major limitations of our study.

Due to the retrospective nature of this study and small numbers, a causal relationship cannot be determined. Further, drug adverse effects and other confounders, such as comorbid conditions, also could not be excluded. 

Acquired inflammatory demyelinating polyneuropathies: clinical and electrodiagnostic features