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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 46  |  Issue : 1  |  Page : 38-43

A series of unfortunate events: Guillain-Barre syndrome on a COVID-positive pregnant patient


Department of Obstetrics and Gynecology, East Avenue Medical Center, Quezon City, Philippines

Date of Submission24-Jan-2022
Date of Acceptance24-Jan-2022
Date of Web Publication15-Apr-2022

Correspondence Address:
Dr. Ma Kristina Barbara O. Reyes
Department of Obstetrics and Gynecology, East Avenue Medical Center, East Avenue, Diliman, Quezon City
Philippines
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pjog.pjog_7_22

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  Abstract 


Pregnancy involves various changes to adapt and ensure the growth and development of the fetus. These changes explain why pregnant women are at high risk for certain diseases. Compared with the nonpregnant, their morbidity and mortality are increased. Severe acute respiratory syndrome coronavirus 2, the causative agent of coronavirus 2019 (COVID-19), has been associated with severe outcomes, especially in pregnant women with a propensity to attack the neural tissue and cause several neurologic manifestations and diseases like Guillain-Barre syndrome (GBS). This is a case report of a 22-year-old G2P0 (0010) who presented with upper respiratory tract infection symptoms and eventually develop an ascending symmetrical limb weakness. This paper aims to: (1) present a case of GBS on a COVID-19 confirmed pregnant woman, (2) discuss the association between GBS and COVID-19, and (3) discuss the intrapartum management in a pregnant woman presenting with GBS.

Keywords: COVID-19, Guillain-Barre syndrome, pregnancy


How to cite this article:
Reyes MO, Nicolas ED. A series of unfortunate events: Guillain-Barre syndrome on a COVID-positive pregnant patient. Philipp J Obstet Gynecol 2022;46:38-43

How to cite this URL:
Reyes MO, Nicolas ED. A series of unfortunate events: Guillain-Barre syndrome on a COVID-positive pregnant patient. Philipp J Obstet Gynecol [serial online] 2022 [cited 2022 May 27];46:38-43. Available from: https://www.pogsjournal.org/text.asp?2022/46/1/38/343236




  Introduction Top


Pregnancy is a dynamic state involving various physiologic and metabolic changes needed to accommodate and meet the demands of the developing fetus and the placenta. These changes explain why pregnant women are more susceptible to acquiring certain infections and diseases, one of which includes COVID-19.[1]

According to the World Health Organization, COVID-19 has caused over 102. One million cases and over 2.2 million deaths worldwide since the start of the pandemic. The infection causes a wide array of symptoms, from flu-like symptoms such as fever, cough, colds, dyspnea, diarrhea to life-threatening respiratory failure. It has been linked with severe outcomes, especially in selected populations including the elderly, immunocompromised, and pregnant women.[2] Case reports have shown that this virus may rarely cause neurologic diseases such as Guillain-Barre syndrome (GBS).[3]

GBS is a rare neurologic disorder in which a person's immune system mistakenly attacks part of its peripheral nervous system. Commonly, it presents as progressive, symmetric muscle weakness accompanied by absent to depressed tendon reflexes, usually after infection. The overall incidence of GBS worldwide is 1–2 cases per 100,000 per year more often affecting the male population.[4]


  Case Report Top


A 22-year-old, G2P0 (0010) at 13 weeks and 3 days age of gestation experienced productive cough with whitish sputum accompanied by clear watery nasal discharge, generalized body weakness, several episodes of vomiting, and dizziness. No fever was noted. She sought consult at the local clinic and assessed to have an upper respiratory tract infection and was given unrecalled medications with no immediate relief of symptoms.

At 20 weeks and 4 days age of gestation, the patient experienced sudden bilateral lower extremity weakness with difficulty in ambulation. After 2 days, there was the progression of weakness to the upper extremities, described as difficulty in grasping things and raising her arms, with associated numbness. She was dyspneic with no other symptoms noted. She was brought to a private hospital where laboratory findings showed decreased serum Potassium at 2.1 mmol/L leading to the assessment of hypokalemic paralysis. Despite potassium correction, there was the persistence of bilateral upper and lower extremity weakness. The patient was assessed by a neurologist with an impression of GBS. Additional workup was not done due to financial constraints. COVID-19 reverse transcriptase–polymerase chain reaction (RT-PCR) testing was done revealing a positive result. The patient was subsequently transferred to a tertiary government hospital.

At the said institution, the patient was noted to have persistence of generalized body weakness with episodes of dyspnea. On admission, she was conscious, coherent, oriented, not in distress, hypertensive at 140/90 mmHg, tachycardic at 115 bpm, nontachypneic, afebrile, and with good O2 saturation at 99%. Further examination showed the presence of rhonchi on the left lower lung field, a soft, nontender abdomen, and good fetal heart tones at 140s. Pertinent neurologic examination revealed the presence of generalized body weakness (manual motor testing [MMT] 2–4/5) associated with the sensory deficit and hypotonic reflexes. During that time, the patient was assessed as a case of pregnancy uterine 22 3/7 weeks age of gestation, not in labor, to consider GBS, gestational hypertension rule out preeclampsia, COVID-19, confirmed-mild. The patient was admitted to the COVID ward and was managed by a multidisciplinary team. Laboratory tests showed an elevated aspartate transaminase and alanine transaminase at 117 and 115, respectively, and an increased urine protein to creatinine ratio of 0.72 indicating preeclampsia. Chest X-ray showed pneumonia. Methyldopa, aspirin, magnesium sulfate, and piperacillin-tazobactam were given. Further workups were done: Lumbar tap showed the inconclusive result, however, on electromyography (EMG) as seen on [Table 1], [Table 2], [Table 3], a diffuse, symmetrical, sensorimotor polyneuropathy predominantly demyelinating in nature, with secondary axonal loss was demonstrated. This may be seen in immune-mediated neuropathies such as late-stage acute inflammatory demyelinating polyneuropathy (AIDP). She was then started on intravenous immunoglobulin 25 g for 5 days which provided a marked improvement in motor and sensory function. After 2 weeks, repeat COVID-19 RT-PCR testing was done which showed a negative result. The patient was subsequently transferred to the regular ward where physical therapy was initiated. She was discharged with normal and stable vital signs, clear breath sounds, and improved muscle strength (MMT of 3–4/5) with the diagnosis of G2P0 (0010) pregnancy uterine 25 1/7 weeks age of gestation, not in labor, GBS, t/c AIDP type, Preeclampsia without severe features, COVID-19, confirmed–recovered.
Table 1: Nerve conduction study of patient

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Table 2: Electromyography

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Table 3: Laboratory results

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In the interim, regular follow-up check-up was done at the tertiary government hospital thru telehealth.

The patient was a coordinated referral at our institution at 37 weeks age of gestation complaining of labor pains.

The past medical and family history was unremarkable. She is a previous smoker and is an occasional alcoholic beverage drinker, with no history of illicit drug use. Her last menstrual period was January 13–16, 2020.

The patient came to the emergency room consciously, coherent, not in respiratory distress, and wheelchair borne, with normal vital signs. The fundic height was 29 cm, and fetal heart tones was at 140s. On internal examination, cervix was 1 cm dilated, beginning effacement, cephalic in presentation, with an intact bag of water at station-2. Neurologic examination showed generalized body weakness (MMT 3–4/5 on all extremities) with hypotonic reflexes.

She was managed as a case of G2P0 (0010) pregnancy uterine 37 weeks AOG, cephalic in labor, GBS, COVID-19-recovered. Laboratory tests showed normal results. The patient was referred to the perinatology service and the plan was assisted vaginal delivery under labor analgesia. Augmentation of labor was initiated and progress of labor was monitored until she delivered to a live, term baby boy via outlet forceps extraction with right mediolateral episiotomy under epidural anesthesia. Postdelivery, no complications were noted. As assessed by the neurology service, no immediate intervention was warranted.

On the fourth hospital day, rehabilitation medicine assessed her to have impaired motor function (MMT 3–4/5) and sensory integrity (70% L2) associated with acute polyneuropathy, GBS. She subsequently underwent physical and occupational therapy to improve both gross and fine motor skills.

On the eleventh hospital day, she was discharged with improved motor skills (MMT 4/5 on all extremities) and sensation. The pulmonary function test was normal. She was advised follow-up at a rehabilitation center for continuity of physical therapy but opted to continue it at home. Currently, her condition and muscle tone have markedly improved. She is now able to walk alone on flat surfaces but still has trouble climbing the stairs. The patient and her baby are both healthy and doing good.


  Discussion Top


COVID-19 infection is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This viral agent enters the human body via two routes: (1) Binding to the angiotensin-converting enzyme-2 (ACE-2) receptor and releasing the viral genome and nucleocapsid protein into the host cell cytoplasm and (2) direct plasma membrane route via transmembrane serine protease 2 (TMPRSS2).[1],[5] The incubation period ranges from 4 to 14 days and it can be transmitted by droplet infection, surface contact, and airborne.[2] It causes nonspecific flu-like symptoms such as fever, cough, colds, dyspnea, nausea, diarrhea, and anosmia. Due to its nonspecificity, its diagnosis may be delayed causing more severe disease if left untreated.[1] High morbidity and mortality are seen among the elderly, immunocompromised, and pregnant women.[2]

Several studies have established that pregnant women are more predisposed to contract COVID-19 infection. Pregnancy initiates changes including (1) hyperventilation secondary to the increased progesterone and estrogen and (2) increased expression of ACE-2 receptor making them more at risk for COVID-19.[1],[3] Progesterone acts as a trigger to the primary respiratory center by reducing the threshold and by increasing the sensitivity of the respiratory center to carbon dioxide while Estrogen increases the number and sensitivity of progesterone receptors within the hypothalamus and medulla. Together, they cause hyperventilation or dyspnea in pregnancy. Hyperventilation causes a person to inhale more air than usual, making them more likely to inhale droplets and aerosols containing viruses like COVID-19.[1],[3] Secondly, during pregnancy, there is an increased expression of the ACE-2 receptor which can be found in many cell types and tissues including the brain. In recent studies, scholars believe the ACE-2 receptor is the “doorknob” for SARS-CoV-2 entering the host cells, and its upregulation is likely to increase the susceptibility to COVID-19. According to Zhao et al., and Narang et al., a high expression of ACE2 receptors seen in pregnant women, increases their susceptibility to SARS-CoV-2. In the United States, 78,129 pregnant women were infected by SARS-CoV-2. In the Philippines, no current data is available as of this writing; however, from March 15, 2020, to March 25, 2021, our institution has documented 89 pregnant women who tested positive for COVID-19.

Our patient, a G2P0 (0010), presented with nonspecific flu-like symptoms and after 7 weeks she developed an ascending symmetric muscle weakness associated with numbness and hypotonic reflexes and she tested positive for COVID-19 infection. On the background of infection, and a presentation of symmetric progressive ascending paralysis, GBS was entertained on our patient.

GBS is a rare neurologic disorder in which a person's immune system mistakenly attacks part of its peripheral nervous system. It is an immune response to a preceding infection, usually respiratory or gastrointestinal, that cross-reacts with the peripheral nerve components thru molecular mimicry.[4] The most common cause is an infection caused by Campylobacter jejuni; however, it can also be caused by other infections like cytomegalovirus, Epstein-Barr virus, and influenza virus (COVID-19). The features of GBS are progressive, fairly symmetric muscle weakness accompanied by absent to depressed tendon reflexes.[4],[5] Diagnosis is mainly clinical but can be supported by cerebrospinal fluid (CSF) analysis and electrodiagnostic studies that would show an albuminocytologic dissociation and decreased motor nerve conduction velocity, prolonged distal motor latency, increased F wave latency, conduction blocks, and temporal dispersion, respectively. Currently, the management of GBS is mainly supportive, with plasmapheresis and immunoglobulin therapy intravenous immunoglobulins as the definitive management.[4],[5] One-third of the patients with GBS would require mechanical ventilation and the most common cause of morbidity is respiratory failure. About 80% of patients with GBS can walk independently 6 months after, 80% fully recover their motor strength a year after and about 5%–10% have incomplete recovery.[4]

GBS is rare during pregnancy. According to Pacheco et al., there is no evidence that pregnancy by itself affects the natural history of the disease.[6] The diagnosis of GBS in pregnant women is no different in the nonpregnant population and would depend on the clinical manifestations of the patient. However, diagnostic tests may be helpful in confirming the diagnosis, or more importantly, in excluding other conditions.

Some literature has stated the association between COVID-19 infection and GBS. As stated before, SARS-CoV-2 enters the host cell through the interaction with ACE-2 receptors. Theoretically, any organ with ACE-2 receptors is potentially susceptible to COVID-19 infection. Although it is principally a respiratory disease, according to studies, it can infect different body sites through ACE-2 receptors, so the various infected organs manifest individual symptoms.[4],[5],[7] According to Paliwal, et al., ACE-2 receptors are expressed on endothelial cells and neurons, this explains why SARS-CoV-2 has a neuro-invasive capacity.[8] Several neurologic manifestations have been reported it includes GBS. Studies show that the time of onset of GBS ranged from 3 days to 4 weeks of the onset of COVID-19; some occur para-infectious and some had postinfectious GBS.[7],[8]

Going back to our patient, she presented with nonspecific flu-like symptoms at the peak of COVID-19 infection. No COVID-19 testing was done during that time. After 7 weeks, she tested positive to RT-PCR COVID-19. According to the Central for Disease Control and Prevention, a person can test positive on RT-PCR up to 12 weeks of infection. Given the presentation of the patient with flu-like symptoms that are typically seen in COVID-19 patients, the occurrence of the symptoms during the peak of COVID-19 infection in our country, and the time frame of only 7 weeks, we can deduce that the preceding infection that our patient has acquired during the first trimester may be attributed to COVID-19 infection. On further workup, CSF analysis and EMG were done which showed results consistent with GBS. As stated from our review of literature, GBS can occur para-infectious or postinfectious secondary to COVID-19 infection. We can presume that the GBS that our index patient had is secondary to COVID-19.

Management of GBS in the pregnant population requires a multidisciplinary team consisting of Obstetricians, Anesthesiologist, and Neurologists and generally does not differ from the nonpregnant population; however, GBS management raises concerns regarding the timing and mode of delivery, and choice anesthesia and analgesia.[9],[10] Timing of delivery is an important decision to make in a pregnant woman diagnosed with GBS. According to some literature, a close follow-up regarding disease progression and maternal hemodynamic status as well as fetal well-being will determine the timing of delivery. Another important decision to make is the mode of delivery. According to Chan et al., despite neurologic deficits, impairment of uterine contraction activity was not observed, and the ability of normal vaginal delivery was possible.[10] Therefore, GBS is not an indication for cesarean section. According to Pacheco et al., the use of forceps or vacuums may be required because of a lack of maternal pushing effort. Hence, the mode of delivery should be tailored according to obstetric indications.[6] Pain control during labor and delivery is essential because patients may have an exaggerated hemodynamic response to labor pain. In the review of literature, regional anesthesia is the preferred type and technique used by most anesthesiologists. Our patient had close antenatal surveillance via telehealth and at 37 weeks she delivered via assisted vaginal delivery under epidural anesthesia to a healthy baby boy with an Apgar score of 4, 6, 9 and birth weight of 2200 g.


  Conclusion Top


In normal pregnancy, there are changes in a woman's body that make them susceptible to certain diseases one of which is COVID-19. COVID-19 infection has caused a variety of symptoms involving different organ systems including the nervous system. A rare complication of COVID-19 infection is GBS. GBS and COVID-19 infection is often diagnosed late due to the nonspecific symptoms they cause; therefore, a high index of suspicion should always be practiced in order not to miss the diagnosis. Guillain-Barre in pregnancy poses a clinical challenge requiring a multidisciplinary approach. Diagnosis is based on clinical features supported by CSF analysis and nerve studies. Management is comprised primarily of supportive care with close respiratory and cardiac monitoring followed by disease-modifying treatment. The timing of delivery should rely mainly on maternal and fetal status; hence, close fetal monitoring and progression of the disease are warranted. The mode of delivery should be tailored individually, mostly based on obstetric indications. GBS alone is not an indication for cesarean delivery. Finally, regional anesthesia is the preferred method for pain management.

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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Narang K, Enninga EA, Gunaratne MD, Ibirogba ER, Trad AT, Elrefaei A, et al. SARS-CoV-2 infection and COVID-19 during pregnancy: A multidisciplinary review. Mayo Clin Proc 2020;95:1750-65.  Back to cited text no. 1
    
2.
Donders F, Lonnée-Hoffmann R, Tsiakalos A, Mendling W, Martinez de Oliveira J, Judlin P, et al. ISIDOG recommendations concerning COVID-19 and pregnancy. Diagnostics (Basel) 2020;10:243.  Back to cited text no. 2
    
3.
Zhao X, Jiang Y, Zhao Y, Xi H, Liu C, Qu F, et al. Analysis of the susceptibility to COVID-19 in pregnancy and recommendations on potential drug screening. Eur J Clin Microbiol Infect Dis 2020;39:1209-20.  Back to cited text no. 3
    
4.
Virani A, Rabold E, Hanson T, Haag A, Elrufay R, Cheema T, et al. Guillain-barré syndrome associated with SARS-CoV-2 infection. IDCases 2020;20:e00771.  Back to cited text no. 4
    
5.
Sedaghat Z, Karimi N. Guillain Barre syndrome associated with COVID-19 infection: A case report. J Clin Neurosci 2020;76:233-5.  Back to cited text no. 5
    
6.
Pacheco LD, Saad AF, Hankins GD, Chiosi G, Saade G. Guillain-barré syndrome in pregnancy. Obstet Gynecol 2016;128:1105-10.  Back to cited text no. 6
    
7.
Webb S, Wallace VC, Martin-Lopez D, Yogarajah M. Guillain-barré syndrome following COVID-19: A newly emerging post-infectious complication. BMJ Case Rep 2020;13:e236182.  Back to cited text no. 7
    
8.
Paliwal VK, Garg RK, Gupta A, Tejan N. Neuromuscular presentations in patients with COVID-19. Neurol Sci 2020;41:3039-56.  Back to cited text no. 8
    
9.
Zilberlicht A. Guillain-barre syndrome in pregnancy – A case report and review of literature. Gyncol Obstet 2016;6:1.  Back to cited text no. 9
    
10.
Chan LY, Tsui MH, Leung TN. Guillain-barré syndrome in pregnancy. Acta Obstet Gynecol Scand 2004;83:319-25.  Back to cited text no. 10
    



 
 
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