Guillain-Barre Syndrome Following Anterior Cervical Spine Surgery and COVID-19 Vaccination: Literature Review with a Case Report

Cavagnaro MJ; Orenday-Barraza JM; Georges J; Baaj AA

Case Report

Austin Neurol & Neurosci. 2022; 5(1): 1027.

Guillain-Barré Syndrome Following Anterior Cervical Spine Surgery and COVID-19 Vaccination: Literature Review with a Case Report

Cavagnaro MJ¹*, Orenday-Barraza JM¹, Georges J² and Baaj AA¹

¹Department of Neurosurgery, University of Arizona College of Medicine, AZ, USA

²Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, USA

*Corresponding author: María José Cavagnaro, Department of Neurosurgery, University of Arizona College of Medicine, 475 N 5^th St, Phoenix, AZ, USA

Received: February 22, 2022; Accepted: March 18, 2022; Published: March 25, 2022

Abstract

Coronavirus Disease 2019 became a pandemic in March 2020 and vaccines were developed as the most efficient and effective means to control the disease. However, during the early vaccination period, side effects were reported. The following presents a case of GBS with a temporal relationship to COVID-19 vaccination occurring in a patient who recently underwent spinal surgery. In addition, a literature review was performed to draw attention to this neurological complication in association with COVID-19 vaccination and/or spinal surgery.

Keywords: ACDF; Cervical myelopathy; COVID-19; Guillain barre syndrome; Vaccine

Introduction

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), became a pandemic in March 2020 [1], causing significant economic and health concerns worldwide. Vaccines were developed as the most efficient and effective means to control the disease, with more than 85 million people fully vaccinated in the USA by March 2021 [2]. During the early vaccination period, side effects were reported, ranging from local pain to respiratory failure and death.

Guillain-Barre Syndrome (GBS) is an acute demyelinating inflammatory polyradiculoneuritis, commonly attributable to antecedent infections or other immunogenic events [3]. It occurs in 0.4-4.0 cases per 100,000 people, and less than 1 case of GBS per 1,000,000 immunized people seems to be related to a vaccine [3]. The role of a vaccine triggering GBS has been only proven with the influenza vaccine from 1976 [4].

We present a case of GBS with a temporal relationship to COVID-19 vaccination occurring in a patient who recently underwent spinal surgery and performed a literature review to draw attention to this neurological complication in association with COVID-19 vaccination and/or spinal surgery.

Methods

A literature search was conducted by 2 independent reviewers (MJC and JMO) from PUBMED and Cochrane databases to identify all the relevant studies that have been published in English addressing a temporal relationship between any subtype of COVID-19 vaccination, spinal surgery and GBS. The search terms included were: “COVID-19”, “SARS-CoV-2 vaccination”, “mRNA-based vaccine”, “vector-based vaccine”, “Guillain Barre Syndrome” “Miller- Fisher syndrome”, “side effect “, “adverse reaction”, “spinal surgery”, “Cervical myelopathy” “ACDF” and “polyneuropathy”. Technical notes, literature review, cadaveric studies as well as publications including pathologies distinct from GBS were excluded from the review.

Results

Both reviewers (MJC and JMO) independently screened abstracts and titles after removing 30 duplicate publications. Search results yielded 27 publications reporting 40 patients with a temporal relationship between COVID-19 Vaccination and GBS, and 14 articles reporting 18 patients with a temporal relationship between spinal surgery and GBS. Cases with a temporal relationship of COVID-19 vaccination, GBS and spinal surgery were not found.

Of the 40 patients with GBS after COVID-19 vaccination, 27 received Oxford/Astrazeneca, 3 Johnson&Johnson, 1 CoronaVac and 1 Moderna. Our case report and eight other patients received Pfizer. All the patients except four developed GBS after the first dose. No data is currently available on patients with GBS after a 3rd dose. The mean age was 59.43 years old with a Standard Deviation (SD) of 14.63 and the mean days and SD latency between vaccination and onset of GBS was 11.9 and 6.25 respectively ranging from 1 to 39 days. The treatment included Intravenous Immunoglobulin (IVIGs) (n = 25), Plasmapheresis (PF) (n = 3), IVIGs and PF (n = 6), steroids (n = 3) and different therapy (n = 3). All the cases were reported in 2021.

Of the 18 cases patients with GBS after spinal surgery, 4 patients underwent to posterior thoracolumbar fusion, 1 lumbar fusion, 4 lumbar laminectomy, 1 endoscopic discectomy, 2 cervical laminoplasty, 2 tumoral resections and 1 after kyphoplasty. Our case report and 2 other cases underwent ACDF surgery. The average age was 56.66 years and the SD between patients was 10.08 years. The mean latency between surgery and onset of GBS was 7.40 days with a SD of 6.7 days and ranged from 3 hours to 25 days. The treatment included IVIGs (n = 11), PF and steroids (n = 1), IVIGs and steroids (n = 2), PF and steroids (n = 1), IVIG and steroids (n = 1), IVIGs and PF (n = 1) and no therapy (n = 1). The cases were reported from 1990 to 2018.

To the best of our knowledge, this is the only reported case of GBS with a temporal relationship to COVID-19 vaccination, occurring in a patient who recently underwent spinal surgery.

Case Description

A 65-year-old male, one-month postoperative C4-C5 Anterior Cervical Discectomy and Fusion (ACDF) for cervical myelopathy, was admitted to the Emergency Department for rapidly progressing weakness and paresthesias to both upper and lower extremities. There were no complications related to his ACDF and his myelopathy was initially improving post-operatively. The patient was then evaluated 2 weeks after surgery, he was asymptomatic, and his physical exam was unremarkable. He denied recent travel, gastrointestinal symptoms nor trauma; however, 9 days before his second admission, he had had a single dose of the Pfizer COVID-19 vaccine.

On examination, there were no mental status or cranial nerve abnormalities. His strength was 4/5 on both upper and lower extremities in addition to areflexia and urinary retention. His sensation was intact. Within forty-eight hours from admission, the patient progressed to severe quadriparesis and respiratory failure; therefore, endotracheal intubation was performed.

Investigations

Naturally, there was a concern of spinal cord compression given his recent surgery, but MRI did not reveal acute compression or post-surgical complications (Figure 1 and 2). Furthermore, a thoraco-lumbar spine and brain MRI showed no abnormalities. The patient denied a previous history of COVID-19 infection and the Coronavirus Cov-2 PCR on admission was negative.

Figure 1: Preoperative MRI (sagittal and axial T2 weighted sequence without contrast) showing a C4-C5 spinal canal stenosis with a hyperintense intramedullary signal suggesting myelopathy.

    
    
    Figure 1: Preoperative MRI (sagittal and axial T2 weighted sequence
without contrast) showing a C4-C5 spinal canal stenosis with a hyperintense
intramedullary signal suggesting myelopathy.

Figure 2: MRI (sagittal and axial T2 weighted sequence without contrast) one month after surgery without any signs of acute compression or post-surgical complications.

    
    
    Figure 2: MRI (sagittal and axial T2 weighted sequence without contrast) one
month after surgery without any signs of acute compression or post-surgical
complications.

A diagnosis of GBS was considered due to the rapidly progressive nature of the patient’s presentation, which was supported by Cerebrospinal Fluid (CSF) analysis showing an albumin cytologic dissociation (protein 105 mg/dL and WBC 10/mm3); and GD1 serum antibodies of 177 IV, which are strongly associated with acute motor and sensory neuropathy (AMSAN), an axonal variant of GBS [5,6]. The clinical picture, as well as the CSF analyses and the presence of GD1 serum antibodies, supported a diagnosis of GBS. Unfortunately, a nerve conduction study was not performed.

Differential Diagnoses

Given his recent surgery, the symptoms, and signs of GBS can be confused for those of spinal cord injury secondary to the procedure. The MRI was useful to rule out the presence of postoperative hematoma, ischemia, and displacement of the implant, instability, and infection. In addition, the presence of flaccid quadriparesis and areflexia on the physical examination supported the diagnosis of peripheral neuropathy. However, there was no history of triggers and the basic peripheral neuropathy screening (Vitamin B12 level, folate level, copper level, VDRL, thyroid hormones, HIV test and protein electrophoresis) was unremarkable. Antinuclear and antineutrophil cytoplasmic antibodies, as well as C3 and C4 levels, were within the normal limits.

Treatment

The patient was admitted to the intensive care unit and closely monitored with regular input from the neurology, neurosurgery and physiotherapy teams. Only two doses (2 g/kg daily) of the IVIG were administered. After an anaphylactic reaction with the second dose of IVIG, the treatment was changed to plasma exchange therapy which was administered on seven occasions with minimal improvement.

Outcome

Although his neurologic symptoms were gradually improving when he was discharged to a rehabilitation center, the patient passed away two months after the admission due to complications associated with his ventilator dependence.

Discussion

Correlation between GBS and common vaccines (HPV, MMR, etc.) has been reported in case reports, but no causation has been demonstrated [7], except with the influenza vaccine in 1976 [4]. Thus, vaccines remain widely authorized as their potential benefits overcome their potential risks.

Less than 12 months from their advent, COVID-19 vaccines have been shown to be safe and effective by manufacturers’ data and findings from large clinical trials [8,9]. Albeit, adverse events have been reported, from mild adverse effects such as local pain, fever, flu symptoms, diarrhea, etc.; to severe cases such as myocarditis, thrombosis, respiratory failure, anaphylaxis, and death [10].

Globally, millions have received COVID-19 vaccines and the results seem to be promising. Sporadic cases of GBS may be temporally associated with COVID-19 vaccination, but causation cannot be determined with case reports. [11] As the knowledge of COVID-19 vaccination grows, cases like this may help identify early neurological, or general complications.

During COVID-19 vaccine clinical trials, 2 cases within the Johnson & Johnson studies developed GBS 10 days after injection; one was in the placebo arm and one was in the active vaccine arm. The fact that one participant of the placebo arm also developed GBS within the same timeline, supports the manufacturer’s argument for a coincidental rather than a causal association [12,13].

Currently, eight cases of GBS have been reported in the literature from the general public after Pfizer COVID-19 vaccination. The first case occurred in December 2020 in the USA in a previously healthy female who received her first dose of Pfizer COVID-19 vaccine and developed her symptoms two weeks after [14]. Five cases were reported after the first dose and two cases after the second dose of Pfizer COVID-19 vaccine [15-21]. Additionally, 27 cases occurred after the first dose of the Oxford/Astrazeneca COVID-19 vaccine [22- 40]. Three cases after Johnson and Johnson, one case after the second dose of CoronaVac vaccine and another case after the second dose of Moderna were also reported (Table 1) [22-40].

Table 1: Summary of Previously Reported Guillain Barré Syndrome after COVID-19 vaccine.




  
    Reference 
    Age (years)/sex 
    Type of vaccine/Doses    number 
    Intervale vaccine-onset    symptoms (days) 
    History/current COVID 
    Associated trigger 
    Treatment 
  
  
    Our case 
    65/M 
    Pfizer (1st dose) 
    9 
    None 
    ACDF surgery 
    IVIG/PF 
  
  
    Waheed et al. 2021 [14] 
    82/F 
    Pfizer (1st    dose) 
    14 
    None 
    None 
    IVIG 
  
  
    Ogbebor et al. 2021 [16] 
    86/F 
    Pfizer (1st    dose) 
    1 
    None 
    None 
    IVIG 
  
  
    Nishiguchi et al. 2021    [18] 
    71/M 
    Pfizer (1st    dose) 
    18 
    None 
    None 
    IVIG 
  
  
    Bouattour et al. 2021    [19] 
    67/M 
    Pfizer (1st    dose) 
    7 
    None 
    None 
    IVIG 
  
  
    čenščák et al. 2021 [20] 
    42/M 
    Pfizer (1st dose) 
    14 
    None 
    None 
    IVIG 
  
  
    Hughes et al. 2021 [21] 
    65/M 
    Pfizer (1st dose) 
    2 
    No clarify 
    None 
    IVIG 
  
  
    Razok et al. 2021 [15] 
    73/M 
    Pfizer (2nd    dose) 
    20 
    None 
    None 
    IVIG 
  
  
    Scendoni et al. 2021 [17] 
    82/F 
    Pfizer (2nd    dose) 
    15 
    None 
    None 
    IVIG 
  
  
    Hasan et al. 2021 [22] 
    62/F 
    Oxford/Astrazeneca (1st    dose) 
    11 
    None 
    None 
    IVIG 
  
  
    Patel et al. 2021 [23] 
    37/M 
    Oxford/Astrazeneca (1st    dose) 
    21 
    None 
    None 
    IVIG 
  
  
    McKean et al. 2021 [24] 
    65/M 
    Oxford/Astrazeneca (1st    dose) Vaxzevria 
    9 
    None 
    None 
    IVIG/MP 
  
  
    Min et al. 2021 [25] 
    58/M 
    Oxford/Astrazeneca (1st    dose) 
    3 
    None 
    None 
    Neuropathic drugs 
  
  
    Min et al. 2021 [25] 
    37/F 
    Oxford/Astrazeneca (1st    dose) 
    4 
    None 
    None 
    Neuropathic drugs 
  
  
    Azam et. al 2021 [26] 
    67/M 
    Oxford/Astrazeneca (1st    dose) 
    15 
    None 
    None 
    IVIG 
  
  
    Allen et al. 2021 [27] 
    54/M 
    Oxford/Astrazeneca (1st    dose) 
    16 
    None 
    None 
    MP 
  
  
    Allen et al. 2021 [27] 
    20/M 
    Oxford/Astrazeneca (1st    dose) 
    26 
    None 
    None 
    MP 
  
  
    Allen et al. 2021 
    57/M 
    Oxford/Astrazeneca (1st    dose) 
    21 
    None 
    None 
    IVIG 
  
  
    Allen et al. 2021 [27] 
    55/M 
    Oxford/Astrazeneca (1st    dose) 
    29 
    None 
    None 
    None 
  
  
    Maramattom et al. 2021    [28] 
    43/F 
    Oxford/Astrazeneca (1st    dose) 
    10 
    No clarify 
    No clarify 
    IVIG 
  
  
    Maramattom et al. 2021    [28] 
    67/F 
    Oxford/Astrazeneca (1st    dose) 
    14 
    No clarify 
    No clarify 
    IVIG/PF 
  
  
    Maramattom et al. 202    1[28] 
    53/F 
    Oxford/Astrazeneca (1st    dose) 
    12 
    No clarify 
    No clarify 
    IVIG 
  
  
    Maramattom et al. 2021    [28] 
    68/F 
    Oxford/Astrazeneca (1st    dose) 
    14 
    No clarify 
    No clarify 
    IVIG 
  
  
    Maramattom et al. 2021    [28] 
    70/M 
    Oxford/Astrazeneca (1st    dose) 
    11 
    No clarify 
    No clarify 
    IVIG 
  
  
    Maramattom et al.    2021[28] 
    69/F 
    Oxford/Astrazeneca (1st    dose) 
    12 
    No clarify 
    No clarify 
    IVIG 
  
  
    Maramattom et al. 2021    [28] 
    69/F 
    Oxford/Astrazeneca (1st    dose) 
    13 
    No clarify 
    No clarify 
    IVIG/PF 
  
  
    Introna et al. 2021 [29] 
    62/M 
    Oxford/Astrazeneca (1st    dose) 
    10 
    None 
    None 
    IVIG 
  
  
    Nasuelli et al. 2021 [30] 
    59/M 
    Oxford/Astrazeneca (1st    dose) 
    10 
    None 
    None 
    IVIG 
  
  
    Oo M. et al. 2021 [32] 
    51/M 
    Oxford/Astrazeneca (1st    dose) 
    14 
    None 
    None 
    IVIG/PF 
  
  
    Oo M. et al. 2021 [32] 
    65/F 
    Oxford/Astrazeneca (1st    dose) 
    7 
    None 
    Influenza Vaccine 
    IVIG 
  
  
    Oo M. et al. 2021 [32] 
    66/M 
    Oxford/Astrazeneca (1st    dose) 
    21 
    No clarify 
    Influenza Vaccine 
    IVIG 
  
  
    Finsterer et al. 2021    [33] 
    32/M 
    Oxford/Astrazeneca (1st    dose) 
    8 
    No clarify 
    No clarify 
    IVIG/PF 
  
  
    Kanabar G, Wilkinson P.    2021 [35] 
    61/F 
    Oxford/Astrazeneca (1st    dose) 
    10 
    No clarify 
    No clarify 
    IVIG 
  
  
    Kanabar G, Wilkinson P.    2021 [35] 
    56/M 
    Oxford/Astrazeneca (1st    dose) 
    9 
    No clarify 
    No clarify 
    IVIG 
  
  
    Nasueli et al. 2021 [30] 
    59/M 
    Oxford/Astrazeneca (1st    dose) 
    10 
    No clarify 
    None 
    IVIG 
  
  
    Kripalani et al. 2021    [40] 
    52/F 
    Oxford/Astrazeneca (1st    dose) 
    11 
    None 
    None 
    IVIG 
  
  
    Tutar et al. 2021 [31] 
    76/M 
    Corono VAC (2nd    dose) 
    5 
    No clarify 
    No clarify 
    No Clarify 
  
  
    Prasad et al. 2021 
    41/M 
    Johnson and Johnson (1st    dose) 
    12 
    None 
    None 
    IVIG 
  
  
    Morehouse et al. 2021    [36] 
    49/F 
    Johnson and Johnson (1st    dose) 
    5 
    None 
    No clarify 
    IVIG/PF 
  
  
    Rossetti et al. 2021 [38] 
    38/M 
    Johnson and Johnson (1st    dose) 
    14 
    No clarify 
    No clarify 
    IVIG 
  
  
    Dalwadi et al. 21 [39] 
    86/F 
    Moderna (2nd    dose) 
    2 
    No clarify 
    No clarify 
    PF 
  
  
    F: Female; M: Male; MP: Methylprednisolone; IVIG: Intravenous    Immunoglobulin; C: Corticosteroids; PF: Plasmaferesis.



Table 1: Summary of Previously Reported Guillain Barré Syndrome after COVID-19 vaccine.

To our knowledge this is the largest literature review of GBS with a temporal relationship with COVID-19 vaccination [33]. At the moment of writing this manuscript, November 2021, 40 cases were reported in the literature.

Furthermore, 130 reports of GBS after Janssen COVID-19 vaccination were received before July 2021 in the Vaccine Adverse Event Reporting System [41-43]. The median time to onset of GBS following vaccination was 13 days [43].

Because our patient underwent surgery one month before the onset of the symptoms, it is important to highlight that surgery has occasionally been associated with the development of GBS across various surgical fields, with a vast majority after spine surgery. Gensicke et al. demonstrated that the relative risk of contracting GBS was 13.1 in surgical patients when compared to the normal population [44]. The pathophysiology of post-surgical GBS is not well understood, but the common pathway involves an autoimmune insult on the nervous system [44]. In our review of the cases reports of GBS, we found 18 cases after spinal surgery with symptoms typically presenting 1-2 weeks postoperatively (Table 2) [22-40]. The temporal relationship of more than 1 month between our patient’s surgery and the development of GBS symptoms, make a causal relationship unlikely based on the current knowledge. However, it remains uncertain if the association of both COVID19-vaccination and surgery made our patient more susceptible to this incident.

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Citation: Cavagnaro MJ, Orenday-Barraza JM, Georges J and Baaj AA. Guillain-Barré Syndrome Following Anterior Cervical Spine Surgery and COVID- 19 Vaccination: Literature Review with a Case Report. Austin Neurol & Neurosci. 2022; 5(1): 1027.

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Reference	Age (years)/sex	Surgery	Intervale vaccine-onset symptoms (days)	Treatment
Dowling et al. 2018 [45]	53/F	L4-L5 endoscopy disectomy	10 days	IVIG
Oku et al. 2018 [51]	66/M	Laminoplasty C3-C6	13 days	MP/IVIG
Rashid et al. 2017 [52]	62/F	Lumbar descompression L3-L4	12 days	IVIG
Chen et al. 2017 [50]	57/M	Lumbar fusion L3-S1	9 days	MP/IVIG 5 days
Sahai et al. 2016 [54]	52/M	Descompression L4-L5	17 days	IVIG
Boghani et al. 2015 [48]	58/M	Descompression L4-L5	3 hours	IVIG/PF
Boghani et al. 2015 [48]	40/M	Laminectomy L4-L5	1 hour	IVIG/PF
Huang et al. 2015 [47]	50/M	Fusion C0-C2 and ACDF C5-c6	7 days	IVIG
Huang et al. 2015 [47]	53/M	Laminoplasty C3-C6	3 days	IVIG
Huang et al. 2015 [47]	69/M	Fusion T10-l5	2 days	IVIG
Huang et al. 2015 [47]	58/M	ACDF and fusion C4-C7	3 days	IVIG
Battaglia et al. 2013 [46]	73/F	Kyphoplasty	7 days	IVIG
Miscusi et al. 2012 [49]	55/M	C5-C7 chordoma resection	36 hours	IVIG
Gensicke et al. 2012 [44]	70/M	Multiple Spine surgeries	No clarify	No clarify
Cheng et al. 2011	59/F	T1-T3 meningioma resection	6 hours	IVIG
Son et al. 2011 [55]	50/M	T10-L2 fusion	8 days	IVIG
Riebel et al. 1995 [53]	62/F	T12- Sacrum	25 days	IVIG/PF/CE
Stambough et al. 1990 [56]	33/F	T5-L2 fusion scoliosis	8 days	PF/CE