key: cord-0972173-nll6lc9b
authors: Chun, June Young; Park, Sohyun; Jung, Jongheon; Kim, Su-Hyun; Kim, Tae-Sung; Choi, Young Ju; Kim, Ho Jin; Eom, Hyeon-Seok; Hyun, Jae-Won
title: Guillain-Barré syndrome after vaccination against COVID-19
date: 2021-12-17
journal: Lancet Neurol
DOI: 10.1016/s1474-4422(21)00416-6
sha: e8ae17a6193638a238f7919dbdd177302912afbc
doc_id: 972173
cord_uid: nll6lc9b

nan

Guillain-Barré syndrome after vaccination against COVID-19 has been reported worldwide. 1,2 Albeit rare, Guillain-Barré syndrome after vaccination is of great public concern given that it could potentially result in life-threatening paralysis. We report the findings of two patients with Guillain-Barré syndrome after receiving the BNT162b2 vaccine (tozinameran, Pfizer-BioNTech) who were in complete remission from diffuse large B-cell lymphoma.

A n 8 0 -y e a r-o l d w o m a n (patient 1) visited the Research Institute and Hospital of National Cancer Center (Goyang, South Korea) on June 30, 2021, and reported a 5-day history of gradual weakness in her right hand and both legs, preceded by a tingling sensation. She was in complete remission from diffuse large B-cell lymphoma; the last round of chemotherapy had been administered in March, 2015. Patient 1 received the second dose of the BNT162b2 vaccine on June 19, 2021.

On neurological examination of patient 1, distal dominant weakness was noted with absent deep tendon reflexes. A nerve conduction study showed axonal type sensorimotor peripheral polyneuropathy. Detailed evaluation is shown in the appendix (pp 1-2). To rule out lymphoma relapse, ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET and CT was performed. Mild-to-moderate irregular increased ¹⁸F-FDG uptake along a neurovascular bundle was observed (figure, video).

Since the initial clinical manifestation in patient 1 was not typical of Guillain-Barré syndrome, highdose methylprednisolone therapy was initiated under the suspicion of inflammatory peripheral polyneuropathy or a lymphoma relapse. However, the symptoms of patient 1 progressed to quadriparesis.

A follow-up nerve conduction study and an electromyographic study revealed sub acute poly radiculoneuropathy. The acute motor and sensory axonal neuropathy form of Guillain-Barré syndrome was suspected, and intravenous immunoglobulin (IVIG; 2 g/kg) was administered. After IVIG infusion, the patient's pain and weakness improved slightly. She was referred to a rehabilitation facility after 22 days of hospital treatment.

A 76-year-old woman (patient 2) presented with a tingling sensation in her upper and lower limbs, which had started from late June, 2021. adverse reaction scale score was 7, suggesting a probable association between the vaccination and Guillain-Barré syndrome. 7 However, we cannot confirm the causal relation between Guillain-Barré syndrome and the BNT162b2 COVID-19 vaccine, since the two cases of Guillain-Barré syndrome reported could be coincidental, and our report presents the temporal relation (within 4 weeks) only. Notably, both patients had underlying B-cell lymphoma. Aberrant B-cell function, even in remission status, could trigger the development of Guillain-Barré syndrome after vaccination and would be a potential predisposing factor. Such an extensive vaccination drive that is underway, including all age groups (from young people to older adults), is an unprecedented event in the COVID-19 era. Therefore, we might now observe the development of Guillain-Barré syndrome among patients with diffuse large B-cell lymphoma.

Collectively, we suggest that clinicians should be vigilant in suspecting a diagnosis of Guillain-Barré syndrome, particularly among patients with B-cell lymphoma.

Additionally, to our knowledge, this is the first report of Guillain-Barré syndrome variants using ¹⁸F-FDG PET and CT. Patient 1 had visited hospital immediately after symptom onset, and ¹⁸F-FDG PET and CT showed mild-to-moderate irregular uptake of ¹⁸F-FDG along the peripheral nerves, possibly related to active inflammatory processes. Considering the previous history of these two patients, neurolymphomatosis could be a differential diagnosis, which we could not completely exclude. 8 Nonetheless, neurolymphomatosis usually exhibits intense ¹⁸F-FDG uptake, up to the maximum standardised uptake values (5·0), with thickening of the involved nerve, and we did not see these findings in patient 1. 9 Large vessel vasculitis would be another differential diagnosis. However, a large vessel, such as the aorta or femoral artery, was not involved, which led us to suspect polyneuropathy compatible with Guillain-Barré syndrome. CSF analysis showed cytoalbuminologic dissociation. The patient was diagnosed with the acute inflamma tory demyelinating polyneuropathy subtype of Guillain-Barré syndrome, and IVIG (2 g/kg) was administered. Proximal weakness of the upper limbs, and the tingling sensation, were relieved. Patient 2 was referred to a rehabilitation facility after 4 days of treatment in hospital.

In South Korea, ChAdOx1 nCoV-19 (AZD1222, Oxford-AstraZeneca) and BNT162b2 vaccines had been predominantly used until August 2021, and thereafter a mixed combination of these vaccines was used (ChAdOx1 nCoV-19 for first dose and BNT162b2 for second dose). In November 2021, use of the ChAdOx1 nCoV-19 vaccine was ceased in South Korea.

In July 2021, the European Medicines Agency and US Food and Drug Administration recommended increased awareness of Guillain-Barré syndrome after ChAdOx1 nCoV-19 and Ad26.COV2.S (Janssen) adenoviral vector vaccines. 3,4 As of Aug 15, 2021, according to the adverse event reports after COVID-19 immunisation in South Korea, acute paralysis events (including Guillain-Barré syndrome) occurred in 620 (0·0059%) of 10 409 265 recipients after at least one dose of the ChAdOx1 nCoV-19 vaccine and in 382 (0·0055%) of 6 908 787 recipients after at least one dose of the BNT162b2 vaccine; no significant difference was noted (p=0·25). 5 A caveat is that cases were not always refined by experienced neurologists.

In this case series, two older women in remission from diffuse large B-cell lymphoma developed Guillain-Barré syndrome (acute motor and sensory axonal neuropathy and acute inflammatory demyelinating polyneuropathy subtypes) after receiving the BNT162b2 vaccine. Patient 1 fulfilled level 2 of the Brighton criteria for diagnostic certainty and patient 2 fulfilled level 1 of these criteria. 6 The calculated Naranjo

Diagnosis of Guillain-Barré syndrome and validation of Brighton criteria

A method for estimating the probability of adverse drug reactions

Immune-mediated neuropathy with anti-ganglioside antibodies in diffuse large B-cell lymphoma

Sciatic nerve neurolymphomatosis: extent and therapy response assessment with PET/CT

A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group (PIG), and endorsed by the ASNC