LEARNING POINTS
Cases of GBS have been reported in association with SARS-CoV-2 infection.
GBS should be considered as possible neurological complication of infection with SARS-CoV-2.
Therapy with immunoglobulin should be initiated along with dexamethasone.
CASE DESCRIPTION
A 65-years-old male patient was admitted to the emergency department with acute progressive symmetric, ascending, flaccid, quadriparesis. Neurological manifestations began with acute weakness of distal lower extremities, four days prior to admission. It quickly progressed from distal to proximal limbs, culminating in quadriparesis two days before admission, and facial paresis bilaterally. He had no urinary or fecal incontinence, or sensitivity alterations. Since the previous day, the patient presented fever and myalgia, and feeling of fatigue.
Medical history included systemic hypertension, diabetes, dyslipidaemia, and previous stroke with no sequelae.
On physical examination, the patient was febrile, hemodynamically stable, respiratory rate 20/minute, and oxygen saturation of 92% on room air. The neurological examination showed normal consciousness and language, symmetric limb weakness with a Medical Research Council (MRC) scale 3/5 in proximal, 4/5 in distal of the upper extremities and 3/5 in proximal, 4/5 in distal of the lower extremities. Deep tendon reflexes were present on admission, but became absent after 2 days. Plantar response was normal. He presented bifacial nerve palsy, but had no sensitive alterations, signs of dysautonomia, meningeal signs or upper motor neuron disorder signs.
Analytical studies showed a slight increase in C-reactive protein (CRP) 6.19 mg/dL and LDH 291 UI/L, and were otherwise unremarkable. Arterial blood gases revealed hypoxia (paO2 61.8 mmHg without supplemental oxygen).
X-ray of the chest showed slight bilateral peripheric ground glass opacities.
Brain and cervical computerized tomography (CT) scan showed no significant alterations.Lumbar puncture was performed and cerebrospinal fluid (CSF) had a mild increase in the protein content (50 mg/dL) and no cells were found, showing an albuminocytologic dissociation.
Nasopharyngeal swab tested positive for SARS-CoV-2 by RT-PCR.
The patient was hospitalized with the presumptive diagnosis of Guillain-Barré syndrome (GBS), concomitant to COVID-19 pneumonia. He received 0.40 g/kg/day intravenous Immunoglobulin for five days, with progressive improvement of muscle strength and resolution of facial palsy.
Further investigation identified no other infectious agent: CFS and blood cultures were negative, as were serologies for syphilis, hepatitis C, human immunodeficiency virus (HIV), Borrelia burgdorferii, herpes simplex, antigenuria for Legionella and Streptococcus pneumoniae. He was immune to hepatitis B, cytomegalovirus and Epstein Barr virus.
On day 11, neurophysiological study was performed with electromyography (EMG), showing slight signs of distal and proximal dysfunction of the cubital right nerve, and proximal dysfunction of the posterior tibial right nerve.
In regard to SARS-Cov-2 pneumonia, the patient was treated with oxygen therapy, dexamethasone 6mg/day, for 10 days, but after 6 days, severe type 1 respiratory failure developed, requiring non-invasive ventilation (NIV) with continuous positive airway pressure ventilation. A lung CT was performed and revealed peripheric diffused consolidations and ground-glass opacities in both lungs. Treatment with Remdesivir was started (initial dose of 200 mg, followed by 100 mg/day, for 4 days), according to practice guidelines at the time. The patient showed improvement in respiratory insufficiency, being able to suspend NIV after 6 days, and he had no need of further oxygen 2 days later.
He was discharged after 2 weeks of hospitalization, with follow up in Neurology consultation, showing significant improvement of neurological symptoms – muscle strength of 5/5 in MRC scale in all segments, except for lower right limb, which showed 4/5, and no facial palsy.
DISCUSSION
In this case-report, we present a patient with GBS concomitant with a SARS-CoV-2 infection.
Recently, cases of GBS have been reported associated with SARS-CoV-2 infection all over the world.1-3 Classic GBS is more frequently postinfectious, developing symptoms 1 to 3 weeks after infection, and that is the case with the great majority of reported cases related to SARS-CoV-2 infection. Most studies have found that the mean time from COVID-19 infection to GBS is nine to fourteen days, but in some reports, the onset of neurologic symptoms overlapped with active SARS-CoV-2 infection4-7, suggesting a parainfectious process, similar to that reported with Zika virus.8 In postinfectious cases, it is presumed that antibodies cross-react by molecular mimicry with specific components of peripheral nerves.9 The cause of nerve injury in parainfectious cases is not clear, but it has been raised the hypotheses of direct damage from the virus or a hyperacute immune response.10
Uncini published a systematic review6 of 42 patients presenting GBS associated with COVID-19, in which the interval between the onset of symptoms of COVID‐19 and the first symptoms of GBS ranged from 3 to 28 days (median of 11.5 days). Of the 42 patients, only 5 presented symptoms of COVID-19 less than a week before GBS symptoms. Another systematic review by Hasan7 included 61 patients, in which the time between COVID-19 and GBS symptoms ranged from 2 to 33 days (median of 14 days).
However, in our case, unlike all the reported cases, the symptoms of GBS begun 3 days before the onset of COVID-19 symptoms.
Although in our case EMG results were not peremptorily diagnostic of GBS, the overall presentation was very suggestive. The patient presented with acute quadriparesis, facial paresis bilaterally, hypoareflexia, respiratory failure and albuminocytologic dissociation in the CSF. A significant limitation is the lack of availability of SARS-CoV-2 serology tests and CSF PCR tests at our centre. Investigation for other infections as a cause of GBS was negative.
These findings were interpreted as a GBS associated with SARS-CoV-2, and treatment with intravenous immunoglobulin and dexamethasone was started. The patient showed improvement of neurological symptoms, nevertheless, he presented a worsening of respiratory symptoms associated with COVID-19 after a week of disease. However, with NIV support, the patient made a full recovery.
The overall presentation and evolution of this case was quite similar to the ones reported in literature. Uncini’s6 reported that most patients displayed the classical sensorimotor demyelinating clinical presentation (71.4%), but all subtypes were reported. Patients presented limb weakness (76.2%), hypoareflexia (80.9 %), sensory disturbances (66.7 %) and facial palsy (38.1%). Respiratory failure was present in 33.3% and 40.5% of patients were admitted in intensive care unit. Almost all patients were treated with intravenous immunoglobulin and/or plasma exchange (92.8%) with rapid improvement or recovery in 62.1% of patients.
However, a recent cohort study by Keddie11 suggested that there is no direct relation between infection by SARS-CoV-2 and GBS. In their study, they found no plausible temporal relationship between COVID-19 and GBS, no correlation between COVID and GBS incidence at regional level, and they found a reduction in cases of GBS in comparison to preceding years. They argue that the lockdown measures introduced to prevent COVID-19 transmission reduced other common transmissible infective GBS triggers, thus reducing GBS incidence. Further studies are required to either prove or exclude a causal link between COVID-19 infection and GBS.
The reported cases of GBS associated with SARS-CoV-2 appear to resemble the classical presentations of GBS that respond to standard treatments. Although the time of onset varies between reports, the mean time from COVID-19 infection to GBS is between nine to fourteen days.
This case is particularly rare because the symptoms of GBS started while the patient was still in an incubation period of infection by SARS-CoV-2, with COVID-19 symptoms starting only 3 days later.
Extensive surveillance of neurological symptoms is required in patients with COVID-19, and this agent should be considered as a possible trigger of GBS, even if patient presents no symptoms of SARS-CoV-2 infection at the time of onset of GBS.
BIBLIOGRAFIA
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