Guillain-Barre syndrome following COVID-19 vaccination: a case report and an updated review

Background: Coronavirus disease-2019 (COVID-19) has caused a pandemic that has recently affected every aspect of life. Fortunately, many vaccines with high safety and efficacy profiles were developed timely to face this pandemic. In a very short time, billions of people were vaccinated. In the meantime, a wide range of neurological syndromes are being reported. Guillain-Barre syndrome (GBS) which is a rare immune-mediated post-infectious peripheral neuropathy was reported after both the COVID-19 infection itself and many types of its vaccines. Method(s): We are reporting a case of post-AstraZeneca vaccine GBS and reviewing the literature of all reported post-COVID-19 vaccines GBS till July 2021. Result(s): 29 adult patients were reported. Of them 58.6% were males. Their mean age is 58.2 years. The median time to clinical onset after vaccine administration was 13.2 days. 86.2% of patients had their symptoms following immunization with the 1st dose of AstraZeneca vector-based covid vaccine. Facial palsy was the most predominant single symptom in 75.8% of patients. Conclusion(s): Guillain-Barre syndrome is a well-recognized but still rare adverse event following vaccination against COVID-19. Although preliminary data incriminates viral vector-based vaccines more than the other types, active post-vaccination surveillance and more powerful statistics are mandatory to reach a solid conclusion regarding the presence of a causal relation.Copyright © 2022

It Takes Two to Make a Thing Go Wrong

Seventy-three-year-old diabetic male was a high-risk transfer from Alaska for respiratory decompensation in the setting of progressive bulbar and proximal weakness. He was diagnosed with COVID-19 two months prior and viral mononucleosis 1 month prior to presentation. While the patient had a fall 3 months prior to presentation, and decreased mobility at home, there was abrupt onset of progressive upper/lower extremity weakness, dysphagia, and difficulties managing secretions 2 weeks prior to presentation. Initial exam was notable for MRC 3-4/5 proximal upper/lower extremity weakness, areflexia, and negative inspiratory force of 224 to 230 cm H20. A subtle periorbital heliotrope rash was documented. Lumbar puncture demonstrated albumino-cytologic dissociation (protein 142 mg/dL, 6 WBCs) and CK remained elevated (1930 U/L) despite intravenous hydration. Outside electrodiagnostic testing demonstrated a sensorimotor axonal neuropathy with questionable myopathic features on needle electromyography. Given concern for an inflammatory neuropathy and concomitant inflammatory myopathy, intravenous immunoglobulin 2G/kg and IV methylprednisolone 1G/day over 5 days was started. He was transferred for further diagnostic workup and supportive care 6 days after presentation and required intubation within 24 hours of admission. Exam showed progressive proximal and distal weakness of the extremities and general areflexia/hyporeflexia. Repeat electromyography confirmed a severe sensorimotor axonal polyneuropathy without acquired demyelinating features and normal repetitive nerve stimulation. While the patient could no longer activate muscles voluntarily, proximal muscles had increased spontaneous activity with predominant myotonia. Neuroaxis imaging was notable only for enhancement of the lumbar nerve roots. Combined vastus lateralis muscle biopsy and serologic testing confirmed a second pathologic process contributing to the patient's weakness. This case highlights the cooccurrence of 2 distinct neuropathological entities, with potential relation to a prior viral infection, and the importance of ancillary testing to guide treatment for acute causes of neuromuscular respiratory failure.

Guillain-Barre syndrome associated with SARS-CoV-2 infection: A case series from 4 Colombian cities during the pandemic

SARS-CoV-2 infection has been associated with multiple neurological manifestations. One such manifestation, which has been described since the early stages of the COVID-19 pandemic and is relevant for current neurological practice, is Guillain-Barre syndrome (GBS). The literature describes neurotoxic mechanisms of the virus itself and the possible pathways by which it may affect the peripheral nerves in experimental studies;however, we still lack information on the mechanisms causing the immune response that gives rise to GBS in the context of SARS-CoV-2 infection. Colombia is one of the Latin American countries worst affected by the pandemic, with the third-highest number of cases in the region;thus, it is essential to recognise GBS, as this potential postinfectious complication may severely compromise the patient's functional status in the absence of timely diagnosis and treatment. We present a series of 12 cases of GBS associated with SARS-CoV-2 infection from hospitals in 4 different Colombian cities and describe the clinical presentation, laboratory and electrophysiological study findings, and treatment.Copyright © 2022 Sociedad Espanola de Neurologia

AZD1222 (ChAdOx1 nCoV-19) Vaccine: Hurdles and Visions

ChAdOx1 nCoV-19 (AZD1222) is a replication-deficient chimpanzee adenovirus vectored vaccine developed by Oxford and AstraZeneca for a disease we all know as Coronavirus, or COVID-19. Ongoing clinical studies reveal that the ChAdOx1 nCoV-19 vaccine has a tolerable safety profile and is effective against symptomatic COVID-19. This vaccine may prove crucial in boosting herd immunity, averting life threatening illness, and relieving the current pandemic. In this mini review, we performed a thorough literature search through PubMed and Google Scholar and reported various case reports associated with complications of the adenovirus-vectored COVID-19 vaccine. Various adverse effects of the ChAdOx1 nCoV-19 vaccine were reported around the globe, which were often serious but rare and developed into life-threatening pathologies such as GBS, thrombocytopenia, demyelinating neuropathies, progressive dementia, cerebral infarction, IgA vasculitis, hemophagocytic lymphohistiocytosis, herpes zoster, cutaneous reactions, and vein thrombosis. These worldwide reported complications, which are usually rare and severe, will aid clinicians in understanding and managing unforeseen situations. There is a need for more research to find out more about these complications and their etiopathogenesis. However, the benefits of these vaccinations for stopping the spread of the outbreak and lowering the fatality rate outweigh the potential risk of the uncommon complications.Copyright © The Author(s) 2023.

Impact of COVID-19 on Guillain-Barre Syndrome in India: A Multicenter Ambispective Cohort Study.

Introduction/Aims: Studies conducted during the coronavirus disease 2019 (COVID-19) pandemic have reported varied data regarding the incidence of Guillain-Barre syndrome (GBS). The present study investigated demographic and clinical features, management, and outcomes of patients with GBS during a specified period of the COVID-19 pandemic, and compared these features to those of GBS in the previous year. Methods: A multicenter, ambispective cohort study including 26 centers across India was conducted. Data from a pre-COVID-19 period (March 1 to August 31, 2019) were collected retrospectively and collected ambispectively for a specified COVID-19 period (March 1 to August 31, 2020). The study was registered with the Clinical Trial Registry India (CTRI/2020/11/029143). Results: Data from 555 patients were included for analysis: pre-COVID-19 (n = 334) and COVID-19 (n = 221). Males were more commonly affected during both periods (male:female, 2:1). Gastroenteritis was the most frequent antecedent event in 2019 (17.4%), whereas fever was the most common event in 2020 (10.7%). Paraparesis (21.3% versus [vs.] 9.3%, P = 0.001) and sensory involvement (51.1% vs. 41.3%; P = 0.023) were more common during COVID-19 in 2020, whereas back pain (26.3% vs. 18.4%; P = 0.032) and bowel symptoms (20.7% vs. 13.7%; P = 0.024) were more frequent in the pre-COVID period. There was no difference in clinical outcomes between the two groups in terms of GBS disability score at discharge and 3 months after discharge. Independent predictors of disability in the pre-COVID period included areflexia/hyporeflexia, the requirementfor intubation, and time to bulbar weakness; in the COVID-19 period, independent predictors included time from onset to admission, intubation, and intubation requirement. The mortality rate was 2.3% during the entire study period (13/555 cases). Discussion: Results of this study revealed an overall reduction in the frequency of GBS during the pandemic. The lockdown likely reduced the risk for antecedent infections due to social distancing and improved hygiene, which may have resulted in the reduction of the frequency of GBS.

Acute motor and sensory axonal neuropathy in a patient with undiagnosed mixed connective tissue disease

Case Report: Acute motor and sensory axonal neuropathy (AMSAN) syndrome is a rare subtype of Guillain-Barre syndrome (GBS) with poor recovery [1]. While respiratory and gastrointestinal infections may precipitate AMSAN, an underlying autoimmune disorder is seldom reported in literature. We herein report the complex case of a patient with undiagnosed, asymptomatic mixed connective tissue disease (MCTD) who developed AMSAN syndrome. Case: A 44-year-old Asian male without medical history presented with progressively worsening weakness of both upper and lower extremities and inability to perform daily activities. His symptoms started 12 weeks prior with difficulty standing from a seated position. He felt subjectively better for some time until a week prior, when he became bedbound. He had diarrhea 6 months ago, with 5-6 loose bowel movements a day for a few weeks. Vital signs on admission was normal. On neurological examination, he was alert and oriented, with bilateral upper and lower extremity flaccid paralysis, diffuse muscle atrophy, bilateral hand and foot drop, negative Hoover sign, diffuse areflexia, and intact sensation. Cerebrospinal fluid (CSF) analysis showed WBC 0 and protein level 136. MRI cervical, thoracic, and lumbar spine were normal. EMG revealed sensory involvement with positive sharp waves in proximal muscles along with fibrillations. Intravenous immunoglobulin (IVIG) was initiated at 0.4 mg/kg for 5 days. Infectious workup for COVID-19, stool culture, HIV, TB, RPR and campylobacter jejuni antibody (Ab), was negative. ANA was positive in a speckled pattern with titres 1:1280, with a positive RNP Ab, SS-A, and RF IgM, IgG and IgA. Rest of the autoimmune workup (anti-dsDNA, anti-CCP, SS-B, aldolase, anti-Jo-1, anti-Scl-70, p-ANCA, c-ANCA, anti-GM1, anti-GQ1b, and anti-GD1a ganglioside Ab) was negative. The myositis specific 11 Ab panel was negative. Despite IVIG therapy, he developed dysphagia, respiratory distress, with a negative inspiratory force of -0, requiring intubation. He had a tracheostomy and PEG tube placed and remains quadraplegic nearly 120 days later. Discussion(s): The authors report a unique case of a patient who became progressively weak over 3 months, leading to complete quadriplegia. Interestingly, this is more consistent with chronic inflammatory demyelinating poly-neuropathy (CIDP), as AMSAN typically develops over a short period of 2 to 4 weeks [2]. Despite having negative anti-GM1 and anti-GD1a Ab (in which positive Ab are pathognomonic but not always present in AMSAN syndrome), the patient had weakness that began in the lower extremities, progressing to paralysis, along with albuminocytological dissociation on CSF analysis, pointing to a GBS diagnosis [3]. He had sensory involvement in the EMG, thus making the diagnosis as AMSAN. He had an undiagnosed, asymptomatic autoimmune process most consistent with MCTD. Whether the two disease processes are related to each other is a concept that has not yet been investigated. Pediatric Clinical Case Reports Concurrent Session Saturday February 4, 2023 1:00 PM Copyright © 2023 Southern Society for Clinical Investigation.

Sequential Bell's Palsy and Guillain-Barre Syndrome in a Child Following COVID-19 Vaccination: A Case Report

Case Diagnosis: A 10-year-old boy with postvaccination Guillain-Barre Syndrome (GBS) and Bell's Palsy Case Description or Program Description: A 10-year-old white Hispanic boy without significant past medical history presented to the emergency room (ER) with new right facial droop two weeks following his second dose of the Pfizer COVID-19 vaccine. He was diagnosed with Bell's Palsy and received a five-day course of steroids. He returned to the ER ten days later with a four-day history of bilateral lower extremity pain, weakness, and progressively worsening gait. His examination was notable for less than antigravity strength throughout the major muscle groups of both lower limbs, in which he also had impaired light touch sensation and areflexia. Setting(s): Pediatric unit of acute care hospital Assessment/Results: Cerebrospinal fluid analysis was notable for elevated protein levels. In the setting of areflexia in the bilateral lower limbs, a presumptive diagnosis of GBS was made and a 5-day course of intravenous immunoglobulin (IVIg) was initiated, with improvement. At time of discharge, he was able to ambulate independently without use of an assistive device. Discussion (relevance): Both GBS and Bell's palsy have been reported following vaccinations. This case is unique in that both occurred sequentially in a pediatric patient within 1 month of the second dose of the Pfizer COVID-19 vaccine. Conclusion(s): Neurological complications of the COVID-19 vaccine include both Bell's Palsy and GBS, which as in this case, may occur sequentially. Prompt initiation of IVIg, steroids, and rehabilitation may result in good recovery.

Miller-Fisher syndrome after first dose of Oxford/AstraZeneca coronavirus disease 2019 vaccine: a case report.

INTRODUCTION: Miller-Fisher Syndrome (MFS) is a variant of Guillain-Barré syndrome (GBS), an acute immune-mediated neuropathy, which manifests as a rapidly evolving areflex motor paralysis. This syndrome presents as a classic triad: ophthalmoplegia, areflexia, and ataxia. MFS is usually benign and self-limited. CASE REPORT: A Caucasian patient was admitted to our hospital with the flu, loss of bilateral strength in the lower limbs and upper limbs and sudden-onset ataxia 7 days after receiving a first dose of the Oxford/AstraZeneca COVID-19 vaccine. On neurological examination, the patient had Glasgow Coma Scale score of 15, with absence of meningeal signs; negative Babinski sign; grade 2 strength in the lower limbs and grade 4 strength in the upper limbs; axial and appendicular cerebellar ataxia; and peripheral facial diparesis predominantly on the right, without conjugate gaze deviation. Cerebrospinal fluid (CSF) was collected on admission, and analysis revealed albuminocytological dissociation with CSF protein of 148.9 mg/dL; leukocytes, 1; chlorine, 122; glucose, 65 mg/mL; red cells, 2; and non-reactive venereal disease research laboratory test result. The COVID-19 IgG/IgM rapid immunological test was negative. Electroneuromyography revealed a recent moderate-grade and primarily sensory and motor demyelinating polyneuropathy with associated proximal motor block. DISCUSSION AND CONCLUSION: Miller-Fisher Syndrome may be related to events other than infections prior to neuropathy, as in the case reported here. The patient presented strong correlations with findings for MFS reported in the literature, such as the clinical condition, the results of electroneuromyography, and results of the CSF analysis typical for MFS. When treatment was provided as proposed in the literature, the disease evolved with improvement. Ultimately, the diagnosis of incomplete MFS was made, including acute ataxic neuropathy (without ophthalmoplegia).

Guillain-Barre syndrome in patients with Coronavirus disease-2019: Report of six cases and review of literature

Background: Few studies have reported the association of Guillain-Barre syndrome (GBS) and coronavirus disease-2019 (COVID-19) infection. In this study, we reported GBS in six patients infected with COVID-19 and reviewed all existing literature about GBS in association with COVID-19. Method(s): This study was performed in three referral centers of COVID-19 in Iran, and six patients with the diagnosis of GBS were enrolled. Patients enrolled in the study with acute progressive weakness according to the demyelinating or axonal variant of GBS, according to Uncini's criteria. Result(s): Four of our patients had axonal polyneuropathy, two patients had demyelinating polyneuropathy, and one patient required mechanical ventilation. All our patients had a favorable response to treatment. In one patient, the GBS symptoms recurred four months after the first episode. Conclusion(s): Limited case reports suggest a possible association between GBS and COVID-19. Such associations may be an incidental concurrence or a real cause-and-effect linkage;however, more patients with epidemiological studies are necessary to support a causal relationship. Copyright © 2020 Iranian Neurological Association, and Tehran University of Medical Sciences.

2022 EAN/PNS GBS Guideline

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. This is the first systematic clinical guideline, developed by an international task force using formal GRADE methodology. The diagnostic criteria remain primarily clinical, based on history and examination findings of acute progressive limb weakness and areflexia. Variants of GBS may include motor GBS, Miller Fisher Syndrome, and regional variants with weakness predominantly in lower limbs, face, or pharynx/neck/ arms. The differential diagnosis is wide. When uncertain, diagnosis may be assisted by nerve conduction tests, raised cerebrospinal fluid protein, and less often by MRI spine with contrast, or serum antibodies to gangliosides (especially for variants) or nodalparanodal antibodies (especially if not improving). Axonal versus demyelinating subtyping does not affect clinical management. A history of recent gastrointestinal or respiratory infection or of surgery may support the diagnosis. The risk of GBS is only very slightly increased after Covid-19 infection and after the adenovirus-vector vaccines to SARS-CoV2 (AstraZeneca or Johnson & Johnson) but not mRNA vaccines. Immune treatment is recommended with intravenous immunoglobulin or plasma exchange, for most patients except those mildly affected or after four weeks from onset. A repeat course is reasonable after a treatment-related fluctuation. Corticosteroids are not recommended. There is no evidence of benefi t from any other disease-modifying treatment. Respiratory function should be monitored by forced vital capacity and single breath count to assess the risk of needing mechanical ventilation, guided by the mEGRIS scale. Pain is very common. It may be musculoskeletal or neuropathic, and treated with gabapentin, tricyclic antidepressants or carbamazepine. Patients who fail to improve should be reassessed for the correct diagnosis and for axonal degeneration. Around 5% of patients with GBS may later develop CIDP but no test can reliably indicate this within the first eight weeks. Nodal-paranodal antibodies should be tested if CIDP is suspected or if the patient is not recovering well. The long-term outcome is less good in patients of older age, with preceding diarrhoea, or more severe weakness, as quantified by the mEGOS scale, and also in patients with smaller motor potential amplitudes or raised serum neurofilament light chain level.

A Case Report of Novel Coronavirus-2019 (COVID-19) Disease and Cytomegalovirus (CMV) Co-Infection: A Lethal Combination

Aim and background: The novel coronavirus-2019 (COVID-19) pandemic is raging all across the world. As we are delving more into the management of COVID-19, many new challenges are emerging, which may pose additional threats. One of these is the emergence or re-activation of concomitant viral infections owing to lymphopenia, use of immunosuppressants, underlying comorbidities, and immune dysregulation. Although we have come across the threat of fungal infections and resistant bacterial infections, experience regarding reactivation or co-infection with other viral infections is still limited. We hereby describe a case of COVID-19 disease with cytomegalovirus (CMV) co-infection. Case summary: COVID-19 with Cytomegalovirus (CMV) Co-infection. A 55-year-old male, COVID unvaccinated, chronic smoker, overweight, and hypertensive patient was admitted to our ICU with a 1-week history of fever, cough, and breathlessness. SARSCoV- 2 reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive. At admission, he had hypoxaemia (SpO2 86% on room air), respiratory rate (RR) 35-40/minute, and ground-glass opacities in chest X-ray involving 50% of bilateral lung parenchyma suggestive of severe COVID-19 pneumonia. He was managed with lung-protective invasive mechanical ventilation, restrictive fluid strategy, 16-18 hour/day proning sessions (4-5), intravenous (IV) remdesivir, IV dexamethasone 6 mg 12 hourly, and enoxaparin thromboprophylaxis. After 2 weeks of ICU stay, weaning was attempted but the weaning attempts failed due to underlying neuromuscular weakness. On examination, bilateral (B/L) cranial nerve palsies, areflexia, and motor power 0/5 in bilateral upper and lower limbs were noticed. A possibility of Guillain-Barre Syndrome (GBS) was kept and IV immunoglobulin therapy was empirically administered for 5 days with some improvement in power up to 1/5 in upper limbs. On day 35 of hospitalization, he developed pancytopenia along with features of deranged liver function and gut dysfunction (in the form of paralytic ileus and abdominal distension). In evaluation, polymerase chain reaction (PCR) for CMV turned out to be positive in blood with a very high viral load.Bone marrow aspiration and biopsy showed hemopoiesis with viral inclusion bodies and haemophagocytosis (HLH). Histological evidence of CMV inclusion bodies was present in the bone marrow besides viremia (detected by PCR for CMV), which confirmed the diagnosis of CMV co-infection. IV ganciclovir was initiated along with steroids in view of HLH. There was a decrease in CMV viral load after initiation of IV gancyclovir with subtle clinical recovery. However, the patient continued to deteriorate and succumbed to his illness in the 8th week of the ICU stay.

A Case Report of Coronavirus (COVID-19) Disease and Herpesviridae Viral Co-Infections: A Lethal Combination? ABS0138)

Introduction: COVID-19 pandemic has affected the whole world. Besides COVID, other viral infections may emerge during the course of the disease owing to lymphopenia, use of immunosuppressants, underlying comorbidities, and immune dysregulation, which may pose additional threats.1 We hereby describe two cases of COVID- 19 with viral co-infections belonging to the Herpesviridae family with undulating clinical course. Case 1: Cytomegalovirus (CMV) Co-infection: A 55-year-old male, COVID unvaccinated, chronic smoker, overweight and hypertensive was admitted to our ICU with a 1-week history of fever, cough, and breathlessness. SARSCoV- 2 reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive. At admission, he had hypoxaemia (SpO2 86%on room air), respiratory rate 35-40/minute, and ground-glass opacities in chest X-ray involving 50% of bilateral lung parenchyma suggestive of severe COVID-19 pneumonia. He was managed with lung-protective invasive mechanical ventilation, restrictive fluid strategy, 16-18 hour/day proning sessions (4-5), intravenous (IV) remdesivir, IV dexamethasone 6 mg 12 hourly, and enoxaparin thromboprophylaxis. After 2 weeks of ICU stay, weaning was attempted but the weaning attempts failed due to underlying neuromuscular weakness. On examination, bilateral (B/L) cranial nerve palsies, areflexia, and motor power 0/5 in bilateral upper and lower limbs were noticed. possibility of Guillain-Barre syndrome (GBS) was kept and IV immunoglobulin therapy was empirically administered for 5 days with some improvement in power up to 1/5 in upper limbs. On day 35 of hospitalization, he developed pancytopenia along with features of deranged liver function and gut dysfunction. In evaluation, PCR for CMV turned out to be positive in blood. Bone marrow aspiration and biopsy showed hemopoiesis with viral inclusion bodies and hemophagocytosis (HLH) [Figs 1 and 2]. A diagnosis of secondary HLH related to CMV was contemplated and IV ganciclovir was initiated along with steroids. Histological evidence of CMV co-infection was present and moreover, the quantitative viral load of CMV showed a decreasing trend after initiating IV gancyclovir. However, the patient continued to deteriorate and succumbed to his illness in the 8th week of the ICU stay. Case 2: Herpes Simplex Virus (HSV) Co-infection: Twenty-three years postpartum female with no comorbidities and uneventful obstetric history was referred to our hospital two weeks after a full-term normal vaginal delivery. She developed generalized status epilepticus on the 10th day of delivery, which was managed with anti-epileptic drugs (AEDs). During the hospital stay, RTPCR for COVID-19 turned out to be positive but she remained asymptomatic and seizures were well-controlled on AEDs. On admission to our hospital, she was fully conscious and alert with no neurological deficits. Notable findings were pancytopenia with megaloblastic features, B/L pedal edema, and hepatosplenomegaly. NCCT brain revealed mild subarachnoid hemorrhage (SAH) along the bilateral parietooccipital region for which conservative management was planned. 2D echocardiography was normal. Ultrasonography of the abdomen showed gross splenomegaly and mild hepatomegaly with mesenteric lymphadenopathy. NCCT thorax and abdomen were unremarkable apart from hepatosplenomegaly. In pancytopenia workup, IgM anti-HSV-1 antibodies turned out to be positive in blood. In addition, tropical workup was suggestive of Leptospirosis (IgM antibodies positive). Serological evidence was suggestive of acute HSV-1 infection (based on antibody titers). Bone marrow workup had features of trilineage hematopoiesis with micronormoblastic maturation consistent with iron deficiency anemia without any evidence of hemophagocytosis. IV acyclovir, IV doxycycline, and iron replacement were added, after which she improved clinically and was discharged in stable condition. Tables 1 and 2 show a detailed description of these cases. Discussion: Herpesviridae family is the most important group of viruses responsible for persistent vi al infections in humans, of which CMV contributes to 60-90% of infections in adults, especially in developing countries.2 In healthy individuals, these viruses are kept dormant by the body's immune mechanisms but in an immunocompromised population, reactivation from the latent state can occur. SARS-CoV-2 infection predisposes patients to concomitant viral co-infections, owing to T-cell lymphopenia, decreased NK cell number, and use of immunosuppressive medications.3,4 The first case of CMV co-infection was first reported by D'Ardes and co-workers in 2020.5 Since then, many studies have been emerging in this area. In an observational study from France, 38 COVID-19 patients on >7 days of MV were studied for HSV and CMV pulmonary co-infections (by quantitative real-time PCR in tracheal samples) out of which 47% of patients had one of these infections (24% HSV, 5% CMV, 18% both).6 Another study looking for HSV-1 in patients on invasive MV found HSV-1 reactivation between days 11 and 40, which correlated with immunological markers of decreased innate immunity.7 A case series looking for CMV infection (by PCR in plasma or BAL) in COVID-19, also found CMV reactivation between day 7 and 45 of illness. Most of these patients were above 60 years of age and immunosuppressed (HIV, diabetes mellitus, medications).8 Although immunocompromised individuals are more vulnerable, healthy immunocompetent adults who are critically ill or on prolonged MV may also be susceptible to these infections.9-12 This may be explained by a state of immunoparalysis inherent to prolonged critical illness. In case 1, an ICU stay of around 9 weeks complicated with recurrent nosocomial infections, multiple blood product transfusions, and steroid usage could have the likely triggers. Whether viral co-infections are merely bystanders or truly pathogenic is difficult to comment but timely management is essential to avoid end-organ damage (EOD) which may occur directly (by enhanced viral load secondary to compromised host immunity) or indirectly (by inflammatory changes consequent to prolonged cell-mediated immunity required to maintain viral dormancy).2-4,13 It also seems imperative to study if a viral co-infection has a proclivity to develop more severe hematological anomalies (besides the inherent risk of HLH with COVID) as was seen in case 1, in which the patient had a downward spiral of illness with multiorgan dysfunction.14-15 Limitations: Dynamics of PCR trends and virology studies of samples from trachea, gut, and urine could not be analysed in our patients. Conclusion: Viral co-infections can occur in COVID-19 disease as these patients are often immunocompromised and critically ill. A high index of suspicion and prompt management is needed to improve the outcome of patients. Patients with organ dysfunctions especially hematologic abnormalities with bone marrow involvement should be worked up in detail to look for concomitant viral co-infections. In the future, large-scale research is needed to better elucidate the relationship between SARS-CoV-2 and other viral co-infections.

Post-acute sequelae of SARS-CoV-2 infection (PASC): peripheral, autonomic, and central nervoussystem featuresin a child

Objective: To describe treatment with intravenous immune globulin (IVIG) of severe central, peripheral and autonomic (CNS, PNS, ANS) post-acute sequelae of SARS-CoV-2 infection (PASC) in a child. Background: PASC is defined as failure to recover from acute COVID-19 in those persistently symptomatic for>30 days from onset of infection with any pattern of tissue injury that remains evolving including the nervous system. Design/Methods: A child underwent extensive evaluation of the CNS, PNS and ANS according to the authors protocol for COVID-19 neurologic illness. Results: A 12-year-old girl was initially well until March 2020 until exposure to other family members testing positive for COVID-19 infection she contracted an upper respiratory infection illness with loss of taste, and excessive fatigue followed in July 2020 by burning, weakness, slurred speech and impaired cognition leading to a bedbound state and a concern she was suffering from conversion disorder. Examination in September 2020 showed mild delirium, tetraparesis, stocking sensory loss and areflexia. Electrodiagnosis showed mixed chronic distal demyelinating and axonal changes. Epidermal nerve fiber studies showed reduced calf and thigh densities. Autonomic studies showed symptomatic hypotension with tilting and reflex tachycardia. Brain FDG PET/MRI showed hypometabolism of bilateral anterior and mesial temporal, superior parietal, and lateral occipital lobes, anterior cingulate cortices, and the cerebellar hemispheres with hippocampus volumes <5% of age-matched controls. Lumbar puncture showed a total protein of 136 mg/dL. EEG and Mayo Clinic ENS2 panel did not show evidence of autoimmune encephalitis. From October 2020 to February 2021, she received monthly 2 g/kg/month of intravenous immune globulin (IVIg) with overall clinical improvement. Conclusions: The underlying basis of PASC, especially in the CNS, has not yet been fully appreciated awaiting controlled clinical and autopsy studies. IVIg is effective initial therapy of PASC to modulate neurologic post-infectious immunity. COVID Long Hauler and Long COVID are inappropriate terms for PASC.

Neurological Complications of COVID-19: Guillain-Barre Syndrome Following Pfizer COVID-19 Vaccine

Objective: The first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in Wuhan, China, in December 2019. In December 2020, the FDA approved two vaccines for the prevention of COVID-19 infection. In the clinical trials of the vaccine, multiple side effects have been reported ranging from mild symptoms including injection site pain, myalgia, fatigue, and fever to more serious side effects including anaphylactic shock. However, Guillain-Barre Syndrome (GBS) after receiving COVID-19 vaccine was not been reported till (February 2, 2021) to the best of our knowledge. We reported the first case of GBS after receiving the first dose of Pfizer COVID-19 vaccine. Background: An 82-year-old highly functional female presented to the emergency department with generalized body aches, paresthesia, and difficulty walking. She received first dose of the Pfizer COVID vaccine two weeks prior to presentation. Physical examination demonstrated 5/5 strength in bilateral upper extremities in proximal and distal muscles, 4/5 in hip flexors and decrease sensation to light touch and pinprick in bilateral lower extremities up to the knees. Areflexia in both upper and lower extremities. Cerebrospinal fluid analysis showed albuminocytologic dissociation (protein of 88 and WBC of 4) suggestive of Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP). MRI lumbar spine demonstrated the enhancement of cauda equina nerve roots consistent with the diagnosis of GBS. The patient completed five days of IVIG with significant improvement and was discharged to acute rehabilitation facility. Design/Methods: NA Results: NA Conclusions: In this pandemic and with ongoing worldwide mass vaccination campaign, it is critically important for clinicians to rapidly recognize neurological complications associated with COVID-19 vaccination. We would like to highlight that the risk of neurological complications or any other adverse effect associated with COVID-19 vaccination is low and the benefits of the vaccination outweigh any potential risks or side effects, both at the individual and society levels.

Sensory Neuronopathy Following COVID-19 Infection: a Case Series

Objective: Various viral infections have been described as causes of acute sensory and autonomic neuronopathy (ASANN). We report on three cases of patients with post-infectious ASANN following COVID-19 infection, that were admitted to our hospital within the span of 4 weeks during a COVID-19 spike of infections in NJ. Background: NA Design/Methods: NA Patient 1: A 49-year-old male presented with a one month history of paresthesias and difficulty ambulating. On exam, he was found to have ataxia on finger to nose and heel to shin, absent reflexes, loss of proprioception and vibratory sense in his fingers and toes with strength intact. He was found to have positive SARS-COV2-IgG. He was never vaccinated and never diagnosed with COVID-19 infection. CSF studies were negative for albuminocytologic dissociation. He received a 5-day course of IVIG and one dose of Rituximab with improvement of sensory ataxia. Patient 2: A 28-year-old female presented with a one-month history of paresthesias and subjective generalized weakness. On exam, she was found to have absent reflexes, loss of proprioception fingers and toes with intact strength. She was found to have positive SARSCOV2-IgM. CSF studies were negative for albuminocytologic dissociation. She received a 5-day course of IVIG with slight improvement of sensory ataxia. Patient 3: A 45-year-old female presented with a several month history of progressive paresthesias, generalized weakness, and difficulty ambulating. On exam, she was found to have mild proximal muscle weakness, profound loss of proprioception and vibratory sense in the hands and feet, truncal ataxia and diffuse areflexia. She was found to be Sars-CoV-2-IgM and IgG positive. CSF study revealed cytoalbuminologic disassociation. She received a 5-day course of IVIG with little clinical improvement. Subsequent EMG/NCS was significant for demyelinating axonal polyneuropathy with axonal loss and autonomic instability. Conclusions: Patients with COVID-19 infection may have a predilection for development of postinfectious ASANN.

Acute Inflammatory Demyelinating Polyneuropathy as the first presenting feature of COVID 19 infection

Objective: To describe a case of a 58-year-old patient who presented to the hospital with Acute Inflammatory demyelinating Polyneuropathy (AIDP) as the first symptom of SARS COVID-19 infection without other classic manifestations of COVID-19 infection. Background: COVID-19 associated Guillain Barre syndrome is now widely reported. In our literature review, the majority of GBS patients had preceding respiratory symptoms of COVID19 but our patient had no other systemic involvement, and his symptoms started noticeably within a short duration of exposure. Design/Methods: Case report. Results: 58-year-old male patient presented to the hospital with bilateral lower extremity weakness, facial diplegia and dysphagia. Patient was tested positive for COVID-19 infection three days prior to the symptom onset due to a work-related exposure. He denied having any flu-like symptoms except generalized weakness. Patient reported progressive lower leg weakness started three days back with associated numbness and radicular pain up to T4 level. On examination, the patient had facial diplegia, areflexia and bilateral lower limb ataxia with the strength of about 3/5. CSF analysis showed albuminocytological dissociation. MRI brain and spine showed faint enhancement of lower lumbar roots. GQ1b antibody was positive on Ganglioside panel. With the clinical criteria and laboratory evidence, patient was diagnosed with AIDP. Patient was started on IVIG but due to lack of improvement after four doses patient was switched to therapeutic plasma exchange. He underwent a total of 7 sessions of plasmapheresis with improvement of motor and sensory symptoms. Conclusions: Although most cases were symptomatic for COVID-19, patients without respiratory or systemic symptoms raises a significant healthcare concern, namely the importance of SARS COVID-19 testing in all patients with suspected GBS during this global pandemic. Early diagnosis of COVID-19 associated GBS is also essential for rapid case isolation.

Acute and Chronic Demyelinating Neuropathies following COVID-19 Vaccination: A Report of Four Cases

Objective: To report demyelinating neuropathies following COVID-19 vaccination. Background: Suspected COVID-19 vaccine-associated Guillain-Barre syndrome and other demyelinating conditions affecting the peripheral nervous system have been reported. The pathophysiologic basis of these associations, and that of vaccination-associated demyelinating neuropathies in general, has not been established. Design/Methods: Case report Results: Four cases of acute and chronic demyelinating neuropathies following COVID-19 vaccination were seen at the University of Nebraska Medical Center from May to September 2021. All were males, ages 26-83 years old. Two received the Pfizer-BioNTech vaccine, one Moderna, and one Johnson&Johnson. Onset ranged from 2-21 days after the final dose of vaccination. The time from symptom onset to neurological evaluation ranged from 3 weeks to 4 months, during which symptoms progressed. All cases presented with progressive numbness, weakness, and areflexia in all limbs;two had difficulty walking. Severe facial diplegia was seen in two cases and other bulbar symptoms in one other case. Three cases had electrophysiologic studies confirming demyelination while one case had findings of subacute polyradiculopathies. Cerebrospinal fluid protein was elevated in two cases and normal in the others. No cases had other co-morbidities or histories suggesting an alternate diagnosis. The diagnosis was acute inflammatory demyelinating polyneuropathy (AIDP) in one case, chronic demyelinating polyradiculoneuropathy (CIDP) in two, and subacute polyradiculopathies in one. The cases with AIDP and CIDP received treatment with intravenous immunoglobulin due to significant motor disability, while the case with subacute polyradiculopathies had spontaneous recovery within 8 weeks. Of the treated cases, two had significant improvement by outpatient follow-up at 2-4 weeks post-treatment and one has yet to follow up. Conclusions: Continued identification and reporting of demyelinating neuropathies following COVID-19 vaccination is essential to determine whether a causative association is present. Prompt evaluation for alternative etiologies is vital and early treatment is recommended.

POS-092 SGLT2 INHIBITOR – INDUCED EUGLYCEMIC DIABETIC KETOACIDOSIS IN GUILLAIN-BARRE SYNDROME: A CASE REPORT

Introduction: Introduction: Euglycemic diabetic ketoacidosis (EuDKA) is a rare but increasingly reported serious adverse effect of SGLT2 inhibitors. There is not much published literature on the incidence of EuDKA and the factors associated with it. Though SGLT2 inhibitors were introduced as glucose lowering agents, recent trials have demonstrated their favourable cardiovascular outcome in heart failure and ability to retard progression of proteinuric kidney disease, including in non-diabetics. Hence use of this class of drugs is anticipated to increase exponentially, given the combined high global burden of diabetes, coronary artery disease and chronic kidney disease. As we embark to use the SGLT2 inhibitors in different clinical scenarios, it becomes imperative to report their adverse effects encountered in uncommon clinical conditions as well. Methods: Case history: A 42-year-old gentleman with history of type 2 diabetes mellitus for 15 years and coronary artery disease, presented with difficulty in climbing stairs and walking for 5 days with progressive difficulty in getting up from bed. He did not have past history of covid infection and had been immunised with 1 dose of covid vaccine. On examination, patient had normal hemodynamics. There was flaccid quadriparesis with areflexia and truncal muscle weakness. Nerve conduction study confirmed acute demyelinating polyradiculoneuropathy. His baseline laboratory investigations revealed normal renal parameters but metabolic acidosis was noted at the time of admission. Patient was started on iv immunoglobulin 2mg/kg and the motor weakness improved from grade 2/5 to 4/5. However, the high anion gap metabolic acidosis worsened over the next 4 days and patient developed acidotic breathing. His sugars were within normal limits and the patient was on metformin, glimeperide, vildagliptin, voglibose and dapagliflozin. As blood lactate levels were normal with urine acetone positivity, euglycemic diabetic ketoacidosis secondary to SGLT2 inhibitor was suspected and all the oral hypoglycemic agents were stopped. He was started on hydration and insulin infusion. After 48 hours of stopping dapagliflozin, acidosis resolved completely and the patient was reintroduced back on the other 4 class drugs. At follow-up, there was no recurrence of acidosis and patient was able to walk with support and physiotherapy. [Formula presented] Results: Discussion: SGLT2 inhibitors cause glycosuria and directly induce glucagon release from pancreas. Combined with insulin deficiency, this results in lipolysis, fatty acid oxidation and ketogenesis. They also cause increased renal reabsorption of ketone bodies. The precipitating factors for EuDKA identified so far include abrupt reduction in insulin dosage, reduced oral intake, infections, surgery, excess alcohol use, volume depletion, type 1 diabetes and heavy physical exercise. This is the first reported case of SGLT2 inhibitor-induced EuDKA in a patient with Guillain-Barre syndrome. As symptoms of dehydration may not be significant due to lack of hyperglycemia in EuDKA, there may be a delay in the diagnosis of this complication. Conclusions: Conclusion: The possibility of EuDKA to be kept in mind while evaluating metabolic acidosis in a diabetic patient on SGLT2 inhibitors. Temporarily withholding the SGLT2 inhibitors during an intercurrent illness will prevent the occurrence of the above serious adverse effect. No conflict of interest

To be, or not to be Guillain-Barré Syndrome.

Guillain-Barré Syndrome (GBS) is currently the most frequent cause of acute flaccid paralysis on a global scale, being an autoimmune disorder wherein demyelination of the peripheral nerves occurs. Its main clinical features are a symmetrical ascending muscle weakness with reduced osteotendinous reflexes and variable sensory involvement. GBS most commonly occurs after an infection, especially viral (including COVID-19), but may also transpire after immunization with certain vaccines or in the development of specific malignancies. Immunoglobulins, plasmapheresis, and glucocorticoids represent the principal treatment modalities, however patients with severe disease progression may require supportive therapy in an intensive care unit. Due to its symptomology, which overlaps with numerous neurological and infectious illnesses, the diagnosis of GBS may often be misattributed to pathologies that are essentially different from this syndrome. Moreover, many of these require specific treatment methods distinct to those recommended for GBS, in lack of which the prognosis of the patient is drastically affected. Such diseases include exposure to toxins either environmental or foodborne, central nervous system infections, metabolic or serum ion alterations, demyelinating pathologies, or even conditions amenable to neurosurgical intervention. This extensive narrative review aims to systematically and comprehensively tackle the most notable and challenging differential diagnoses of GBS, emphasizing on the clinical discrepancies between the diseases, the appropriate paraclinical investigations, and suitable management indications.