|Ahead of print publication
Axonal excitability findings in acute inflammatory demyelinating polyneuropathy related to SARS-CoV-2
Abir Alaamel1, Rıfat Şahin1, Merve Hashan2, Tutku Taşkınoğlu3, Tuğba Özel1, Nazan Şimşek Erdem1, Hilmi Uysal1
1 Department of Neurology, Akdeniz University Faculty of Medicine, Antalya, Turkey
2 Department of Emergency Medicine, Akdeniz University Faculty of Medicine, Antalya, Turkey
3 Düzen Laboratory Group, Ankara, Turkey
|Date of Submission||06-Jun-2021|
|Date of Decision||25-Aug-2021|
|Date of Acceptance||26-Aug-2021|
|Date of Web Publication||24-Feb-2022|
Department of Neurology, Faculty of Medicine, Akdeniz University, Dumlupınar Bulvarı, 07058 Campus, Antalya
Source of Support: None, Conflict of Interest: None
Guillain–Barré syndrome (GBS) is a disorder of the peripheral nervous system characterized by acute-onset ascendance paresis. We present a patient who was diagnosed as having facial-onset acute inflammatory demyelinating polyneuropathy after being infected with SARS-CoV-2. A 51-year-old man presented to the emergency department with facial diplegia. He then developed bilateral ascendance paralysis. He had noticed that for 1 month, he had smell and taste disturbances. SARS-CoV-2 infection was suspected. Nasopharyngeal swab polymerase chain reaction test was negative, but anti-SARS-CoV-2 antibody was found to be positive. A nerve conduction study showed prolonged motor distal and F wave latencies with decreased motor and sensory compound muscle action potential amplitudes. Lumbar puncture revealed albuminocytologic dissociation. According to the neurologic examination and laboratory findings, the patient was diagnosed as having acute inflammatory demyelinating polyneuropathy. An axonal excitability study revealed fanning in pattern with prolonged refractoriness, which indicates nodal sodium channel disturbances. Facial-onset SARS-CoV-2–related GBS has been rarely reported; however, facial involvement seems to be one of the features of the neurologic findings.
Keywords: Axonal excitability, facial diplegia, Guillain–Barré syndrome, polyneuropathy, SARS-CoV-2
|How to cite this URL:|
Alaamel A, Şahin R, Hashan M, Taşkınoğlu T, Özel T, Erdem N&, Uysal H. Axonal excitability findings in acute inflammatory demyelinating polyneuropathy related to SARS-CoV-2. Neurol Sci Neurophysiol [Epub ahead of print] [cited 2023 Feb 4]. Available from: http://www.nsnjournal.org/preprintarticle.asp?id=338322
| Background|| |
Guillain–Barré syndrome (GBS) is a disorder of the peripheral nervous system characterized by acute-onset ascendance paresis.
Neurological involvement associated with SARS-CoV-2 has been reported in the literature. We present a patient who was diagnosed as having facial-onset acute inflammatory demyelinating polyneuropathy after being infected with SARS-CoV-2.
| Case Presentation|| |
A 51-year-old man who works as a gardener in a hotel was admitted to the emergency department with difficulties in eye closure. Speech difficulties were detected after 2 h. Weakness in the legs was seen 6 h after admission, even though the patient came to the emergency department without any lower extremity weakness. He had no symptoms of shortness of breath, cough, sputum, or diarrhea. He had experienced taste and smell disturbances 1 month ago, which lasted for 4 weeks. He had no symptoms regarding smell and taste when he was admitted to the hospital.
A physical examination revealed bilateral peripheral facial paralysis. The motor examination was normal. Deep tendon reflexes were hypoactive in the upper extremities and absent in the lower extremities. A sensory examination was normal. After 2 days of clinical follow-up, a motor examination of the bilateral proximal lower limb weakness revealed proximal 3/5 and distal 4/5 according to the Medical Research Council (MRC) score. Deep tendon reflexes were absent in the upper and lower extremities. The examination of the remaining cranial nerves was normal. Lumbar puncture showed 240 mg/dL protein level and no cells per mm3, indicating albuminocytologic dissociation. A nerve conduction study revealed that the median and tibial nerve distal motor and F wave latencies were prolonged (R median nerve distal motor latency: 4.9 ms; L median nerve distal motor latency: 4.9 ms; R tibial nerve distal motor latency: 6.51 ms; L tibial nerve distal motor latency: 6.98; L tibial nerve F wave latency: 61.15 ms). Soleus H reflexes were bilaterally absent. Compound muscle action potential amplitudes of nasal, orbicularis oris, and orbicularis oculi muscles were bilaterally decreased with postauricular stimulation of the facial nerve. Blink reflexes were absent bilaterally [Figure 1].
|Figure 1: Nerve conduction study. There was no response in the blink reflex. Median and tibial conduction velocities and motor distal latencies were longer than normal. Right median nerve motor distal latency was 4.90 ms. Right median nerve velocity was 51.2 m/s. The right median distal amplitude was 14 μV. Right tibial nerve motor distal latency was 6.51 ms. The motor distal amplitude of the right tibial nerve was 4.5 μV. Right tibial nerve motor velocity was 49.2 m/s|
Click here to view
According to the patient's history, neurologic examination, and laboratory findings, the patient was diagnosed as having acute inflammatory demyelinating polyneuropathy. Intravenous immunoglobulin (IVIG) therapy was given to the patient for 5 days. The dose was 0.4 g/kg/day. After 5 days of admission, the patient was unable to move his legs. Upper extremity MRC scores were 4+/5 bilaterally proximal and distal. According to the patient's anamnesis, he had experienced taste and smell disturbances for the last month. Accordingly, a nasopharyngeal swab SARS-CoV-2 polymerase chain reaction test was performed, which was negative. Then, the SARS-CoV-2 antibody test was also performed, which was positive. An antiganglioside panel was also studied, and there was no positive value. The subject was considered as having SARS-CoV-2–related acute inflammatory demyelinating polyneuropathy.
Three weeks after the IVIG therapy, when he was discharged, he was ambulatory with support. His taste and smell examinations were normal. Median and tibial nerve axonal excitability testing was performed to reveal the mechanism underlying the peripheral nervous system involvement associated with SARS-CoV-2. To evaluate the axonal excitability properties of the patient, the QTRAC-S system was used. Statistical analysis was performed using the QTrack-P software. (UCL Institute of Neurology, London, UK, available from Digitimer Ltd at www.Digitimer.com). No specific statistical testing was performed. Our patient's values were compared with those of a control group consisting of nine healthy subjects from our laboratory. The mean age of the control group was 18.44 ± 0.852 (mean ± standard deviation) years. The values of the patient were compared with the values in the 95% confidence interval (CI) range formed by the control group. P < 0.05 was considered statistically significant. The axonal excitability study showed normal properties in the median nerve. Axonal excitability findings of the tibial nerve showed a prolonged relative refractory period (RRP) (P = 0.016), decreased superexcitability (P < 0.001), decreased strength duration time constant (SDTC) (P = 0.005), and a change in TEd (10–20 ms) (P = 0.048), TEd (peak) (P = 0.006), TEd (40–60 ms) (P = 0.023), TEd (90–100 ms) (P = 0.005), TEd20(peak) (P = 0.0446), and rest resting current/voltage (I/V slope) (P = 0.0163) [Figure 2].
|Figure 2: Tibial nerve motor axonal excitability findings. Axonal excitability parameters of the case. The dashed lines show the 95% confidence interval. (a) Current-threshold relationship. (b) Strength-duration time constant. (c) Threshold electrotonus. (d) Recovery cycle.Our case; demonstrating threshold reduction in threshold electrotonus (fanning in) and reduction of superexcitability in recovery cycle with prolonged relative refractory period in motor tibial nerve. Strength-duration time constant has decreased. Current-threshold relationship showes increased excitability to depolarizing current and decreased excitability to hyperpolarizing current|
Click here to view
At the follow-up examination of the patient 6 months later, axonal excitability parameters were in the 95% CI compared with the normal controls [Figure 3].
|Figure 3: Axonal excitability of the tibial nerve 6 months after onset of the disease was in a normal range when compared with control group. (a) Currentâ€'threshold relationship. (b) Strength duration time constant. (c) Threshold electrotonus. (d) Recovery cycle|
Click here to view
| Discussion|| |
Patients with GBS have been reported by Toscano et al. One of the five had facial diplegia. Paresis or paresthesia appeared 5–10 days after the onset of fever, cough, anosmia, and ageusia-like symptoms. Facial-onset SARS-CoV-2–related GBS cases have been reported rarely; however, facial involvement seems to be one of the features of the neurologic findings. Our patient had anti-SARS-CoV-2 antibody positivity. Therefore, we diagnosed our patient as having SARS-CoV-2–related acute inflammatory demyelinating polyneuropathy.
Axonal excitability is one of the neurophysiologic techniques used to study neurophysiologic mechanisms that underlie neurologic diseases. Measuring membrane potential changes with different types of stimuli provides the possibility to understand the channel dynamics in vivo in human axons. Immune-mediated neuropathies, hereditary neuropathies, epilepsy, neurodegeneration, metabolic neuropathy, neurotoxicity, and trauma are some of the neurologic conditions that have been studied using axonal excitability techniques. Previous studies showed normal axonal excitability properties of the median nerve in acute inflammatory demyelinating polyneuropathy. This may be due to sparing the portion of the median nerve at the site of the stimuli. However, these methods have not been used to investigate distal nerves such as the tibial nerve. Our patient's median nerve axonal excitability parameters were in the normal 95% CI range. However, axonal excitability of the tibial nerve revealed a fanning in pattern with prolonged refractoriness. This may indicate altered sodium channel function in this case [Figure 2]. This is the first case report to establish the axonal excitability properties of SARS-CoV-2–related GBS. To the best of our knowledge, this is the first tibial nerve axonal excitability study in GBS. Considering that distal involvement is prominent in acute inflammatory demyelinating polyneuropathy, the axonal excitability features in the tibial nerve are expected to be more pronounced than in the median nerve. As in our case, median nerve axonal excitability parameters can be in the 95% CI range.
We would like to thank the Düzen Laboratory Group for kind support.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
van den Berg B, Walgaard C, Drenthen J, Fokke C, Jacobs BC, van Doorn PA. Guillain-Barré syndrome: Pathogenesis, diagnosis, treatment and prognosis. Nat Rev Neurol 2014;10:469-82.
Baysal-Kirac L, Uysal H. COVID-19 associate neurological complications. Neurol Sci Neurophysiol 2020;37:1. [Full text]
Kiernan MC, Burke D, Andersen KV, Bostock H. Multiple measures of axonal excitability: A new approach in clinical testing. Muscle Nerve 2000;23:399-409.
Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, et al
. Guillain-Barré Syndrome Associated with SARS-CoV-2. N Engl J Med 2020;382:2574-6.
Kiernan MC, Bostock H, Park SB, Kaji R, Krarup C, Krishnan AV, et al
. Measurement of axonal excitability: Consensus guidelines. Clin Neurophysiol 2020;131:308-23.
[Figure 1], [Figure 2], [Figure 3]