Guillain-Barre Syndrome With Concomitant Severe Preeclampsia: A Case Report

With an estimated 100,000 new cases yearly worldwide, Guillain-Barre syndrome (GBS) is the most common cause of flaccid paralysis. GBS is exceedingly rare in pregnancy and carries high maternal and fetal risk. We report a case of a 38-year-old essential primigravida who presented at 38 weeks six days gestational age with ascending paraplegia progressing to dysarthria, dysphagia, and facial weakness. A clinical diagnosis of GBS was made in an outside institution, supported by elevated protein on lumbar puncture. During the antepartum period, a diagnosis of gestational hypertension progressed to preeclampsia with severe features when a sudden rise in liver function tests occurred. The patient underwent an uneventful planned cesarean delivery but could not be extubated due to respiratory failure. After a 20-day critical care admission, she was extubated and had an improvement in neurologic status to near her baseline.


Introduction
Guillain-Barre syndrome (GBS) is the most common cause of flaccid paralysis, with an estimated 100,000 new cases per year worldwide [1]. It is a progressive neurologic disease that typically presents with symmetrical weakness and paresthesia of the distal lower extremities that ascends and can ultimately result in respiratory failure if left untreated [1][2][3]. GBS is often preceded by an infection, frequently with Campylobacter jejuni [1,2]. When GBS is diagnosed, supportive care is the mainstay of treatment, with considerations given for intravenous immune globulin (IVIG) and plasma exchange. Plasma exchange in appropriately selected patients may prevent permanent nerve damage and respiratory failure [4]. Although rare during pregnancy, GBS is associated with high maternal and perinatal morbidity and mortality [5]. The mortality rate has been reported to range between 7% and 25% in patients with pregnancy compared to 3% to 13% in patients with no pregnancy [5].
Our patient presented from a referring hospital with the diagnosis of GBS at 38 weeks and six days gestation. During her hospital course, she developed elevated blood pressure and liver enzyme function tests (LFTs) twice the upper limit of normal, concerning preeclampsia with severe features. There is a dearth of literature describing cases involving pregnant women diagnosed with GBS with concomitant preeclampsia with severe features.

Case Presentation
A 38-year-old primigravida at 38.6 weeks gestational age (WGA) presented to our hospital as a transfer of care for the management of GBS. Her prenatal history had previously been unremarkable. At 31.2 weeks, she received her tetanus, diphtheria, and pertussis (TdAP) and influenza vaccinations and reported that she subsequently developed a flu-like illness for three days that self-resolved. Five weeks later, she began to feel bilateral tingling and numbness in her upper and lower extremities followed by progressive leg weakness. Her weakness progressed to the point that she became unable to walk or support herself. Four days later, she developed left facial weakness with mild dysphagia, dysarthria, and right facial weakness following shortly thereafter. No associated respiratory or cardiovascular symptoms were present at that time. Imaging studies were unremarkable, but cerebrospinal fluid analysis showed albuminocytologic dissociation with elevated protein of 172, polymorphonuclear cells 7, red blood cells 0, glucose 54, consistent with GBS, and IVIG was initiated at 0.4/kg per day for five days.

Initial diagnosis/assessment
Examination revealed areflexia of the lower extremities, hyporeflexia of the upper extremities, and flaccid paralysis. Hours after admission, the patient was noticed to have mild dysphagia and dysarthria followed by right facial weakness. Respiration and mentation were intact. No shortness of breath, bowel/bladder incontinence, or autonomic symptoms were reported. Her speech was fluent but slightly dysarthric. Her facial sensation was intact, but she could not close both eyes or smile. She had decreased muscle strength of 3/5, mainly in the lower extremities, and a moderate bilateral upper extremities weakness of 4/5. Light touch sensation was preserved, but subjective sensation to pinprick was diminished below mid-thigh, and proprioception was completely absent.
She was afebrile, saturating 99% without ventilatory support, but was noted to have an elevated blood pressure of 143/78. Per the record review, the patient had one additional mild-range blood pressure during her admission to the hospital before the transfer, and she was diagnosed with gestational hypertension. Labs to evaluate for preeclampsia were performed and were notable for an elevated urine protein/creatinine ratio of 0.31, and LFTs twice the upper limit of normal with aspartate aminotransferase (AST) of 161 and alanine transaminase (ALT) of 202. Based on these laboratory abnormalities, the patient was diagnosed with preeclampsia with questionable severe features due to elevated LFTs in the setting of IVIG use. A multidisciplinary meeting to discuss management options was held and included neurology, obstetrics, pediatrics, and anesthesia. The decision for cesarean delivery was made due to the worsening maternal condition, including hoarseness and dysphonia in the setting of preeclampsia with possible severe features. She was given antiemetic prophylaxis along with sodium citrate. However, she was not started on medication for seizure prophylaxis at this time, given the uncertain presence of severe features.
Standard American Society of Anesthesiology (ASA) monitors were applied. Two large-bore intravenous lines and an arterial line were placed. A modified combined spinal epidural was performed in the lateral position at the level of L3-L4, using 1.2 mL of bupivacaine 0.75% with 15 mcg of fentanyl and 0.1 mg of Duramorph in the intrathecal space. A T6 anesthetic level was slowly achieved using the epidural catheter to prevent profound hemodynamic changes. Supplemental oxygen was given through a nasal cannula, and a phenylephrine 20 mcg/minute infusion was started to prevent hypotension. The patient remained stable throughout the surgery.
Cesarean delivery was uncomplicated, and the patient delivered a male infant weighing 2,910 g, with an Apgar score of 9/9/9 and an estimated blood loss of 600 mL. Following delivery, the patient was transferred to the stepdown intensive care unit (ICU) where she was managed with Keppra 500 mg twice a day (BID) for 24 hours for seizure prophylaxis. Magnesium sulfate was avoided due to potential respiratory compromise. She received two additional IVIG treatments for a total of five. Her blood pressure remained mildly elevated, and her transaminitis showed a downward trend but did not fully normalize, with an AST level of 67 and an ALT level of 79. Despite the ongoing administration of IVIG, a formal diagnosis of preeclampsia with severe features was established due to the persistent downward trend of LFTs postpartum. Magnesium was still avoided at this time. She continued to report dysarthria and dysphagia postoperatively but had improved sensations in the lower extremities. She retained good respiratory function saturating 100% on room air postoperatively.
The patient was downgraded from the ICU to the intermediate medical care unit (IMCU) on postoperative day 2 and continued to meet postoperative milestones. She was then transferred to the internal medicine inpatient team, then to the physical medicine and rehabilitation center. Throughout her hospital stay, negative inspiratory force and vital capacity measurements were conducted to monitor her respiratory status. Additionally, daily venous blood gases were obtained to assess her respiratory function. Vital capacity was 2.5 at baseline and remained stable. She did not need respiratory support. At the time of discharge, she had persistent decreased sensation in her bilateral lower extremities and bilateral paresthesia in her upper extremities.
Her motor function is progressively improving, and her speech has normalized. She is using a walker and continuing her physical rehabilitation therapies. She does not have any residual respiratory compromise.

Discussion
While GBS in pregnancy is rare, it is important to diagnose and treat it promptly to reduce the significant risk of morbidity and mortality. This syndrome in pregnancy has an estimated incidence between 1.2 and 1.9 cases per 100,000 people annually [6]. Association with an increased need for ventilator support and maternal mortality makes anesthesia management paramount to improve patient outcomes. Peripheral nerve demyelination can be triggered by infection or less commonly by surgery and rarely by vaccination [7].
Cases of GBS in pregnancy without concomitant preeclampsia with severe features have been described and are listed in Appendix. However, to the authors' knowledge, this is the first case report to document GBS in pregnancy with concomitant preeclampsia with severe features. Preeclampsia is a hypertensive disorder of pregnancy that typically presents with new-onset hypertension and proteinuria after 20 weeks of gestation [8]. Preeclampsia is an increasingly common disorder and is a major cause of maternal and fetal morbidity and mortality [9].
Our patient developed symptoms of GBS four weeks after receiving the TdAP and influenza vaccinations.
Although GBS is most often preceded by infectious etiologies, it has been associated with other antecedent events, including vaccinations [1,10]. In 1976, the National Influenza Immunization Program was suspended because of an increase in the reports of GBS symptoms following influenza vaccination [10]. An epidemiological study of these reports found an eightfold increased risk of developing GBS after receiving the influenza vaccination that year [11]. Since then, there have been additional studies that have shown an increased risk of GBS following seasonal influenza vaccination [11]. When the TdAP vaccination was approved for use in 2005, adverse effects, including GBS, were monitored [12]. GBS after the TdAP vaccination was compared to the background risk of GBS, and they found a relative risk of 1.60 [12]. Based on the available evidence, it was determined with relative confidence that the TdAP vaccination carries a risk of no more than approximately 1 additional case per 100,000 doses [12]. In light of the safety profile and benefits to the fetus, the American College of Obstetricians and Gynecologists (ACOG) recommends that all pregnant women receive the TdAP vaccination during each pregnancy [13]. ACOG also recommends that women who are or will be pregnant during influenza season should receive the annual influenza vaccination [13].
GBS is generally treated with a five-day course of IVIG [14]. The treatment does not differ in pregnant versus nonpregnant patients [15]. For non-obstetrical-related conditions, IVIG is recommended in pregnant patients as indicated for nonpregnant patients [15]. Another option for treatment includes plasma exchange (200-250 mL/kg) for five sessions but was deferred in favor of IVIG in our case [14]. Our patient's course was further complicated by her new diagnosis of preeclampsia with possible severe features based on mild-range blood pressures and lab abnormalities, including LFTs twice the upper limit of normal and new-onset proteinuria. Despite the potential for IVIG therapy to induce transaminitis, the decision to proceed with delivery was made based on the presence of preeclampsia beyond 37 weeks of gestation and the deterioration of the maternal condition in relation to her underlying GBS. ACOG recommends delivery rather than expectant management beyond 37 weeks for gestational hypertension or preeclampsia without severe features or beyond 34 weeks gestation for women with preeclampsia with severe features. While the initiation of magnesium sulfate therapy for seizure prophylaxis is recommended for preeclampsia with severe features, we did not initiate it in this case due to an unclear diagnosis of preeclampsia with severe features and due to the potential for further respiratory compromise [16]. Although controversial, at the recommendation of neurology and the ICU teams, we administered Levetiracetam for 24 hours after delivery for seizure prophylaxis.
The mode of action for magnesium sulfate in the prevention and treatment of eclamptic seizures is not clearly understood. The anticonvulsant activity may be mediated by magnesium's role as an N-methyl-Daspartate (NMDA) antagonist, which may prevent and control eclamptic seizures by inhibiting NMDA receptors and blocking the neuronal damage associated with ischemia. Another potential mechanism is that magnesium sulfate may induce cerebral vasodilation, resulting in a reduction of cerebral ischemia. Additionally, magnesium's calcium antagonist and smooth muscle relaxant effects could help restrict paracellular transport of vascular contents and decrease the factors that contribute to cerebral edema and seizure activity. Side effects of magnesium sulfate include flushing, muscle weakness, and nausea. Serious adverse effects such as respiratory and cardiac arrest are rare, but if they do occur are potentially lifethreatening. Although respiratory muscle paralysis only occurs at magnesium serum concentrations at or greater than 7 to 8 mmol/L, magnesium sulfate was not given due to the theoretical risk of potential further respiratory compromise [17].
One of the most serious complications of GBS during anesthesia is broncho-aspiration due to bulbar dysfunction [18]. Other considerations for patients include perioperative respiratory insufficiency due to muscle weakness. If general anesthesia is considered, succinylcholine should be avoided and replaced with a nondepolarizing muscle relaxant due to an increased risk of hyperkalemia. However, the use of nondepolarizing neuromuscular blocking agents on these patients with GBS presents the risk of prolonged blockade, requiring ventilatory support postoperatively [19].
The neuraxial technique should be managed with caution due to autonomic dysfunction with possible hemodynamic instability and autonomic hyperreflexia-type reactions. Arrhythmias and cardiac arrest could also be anticipated after neuraxial blockade [20]. Another risk in these cases is venous thromboembolism, often necessitating the administration of anticoagulation therapy in patients [21].
Anesthetic management of these patients should always include a multidisciplinary approach to facilitate the best clinical outcomes intra-and postoperatively. The anesthetic technique for pregnant women with GBS requiring cesarean delivery remains at the discretion of the specialist, who should be guided by the clinical conditions and comorbidities of each patient. In our case, the patient had stable respiratory mechanics, and the decision was made to employ the neuraxial technique.

Conclusions
GBS is exceedingly rare in pregnancy and carries high maternal and fetal risk. This case is the only case to our knowledge involving the management of GBS in a pregnant patient with a concomitant diagnosis of severe preeclampsia. In these rare cases, delivery timing should be individualized and dependent on maternal clinical status. In situations of impending respiratory failure, an emergency cesarean section is required at gestational ages at or beyond viability. Future studies are needed to examine the laboratory diagnosis of preeclampsia in circumstances with confounding factors, as a diagnostic method exclusive to preeclampsia does not exist. This investigation is even more urgent in light of similar presentations seen with SARS-CoV-2.