key: cord-0923349-hg16yw1l
authors: Gupta, Subhadeep; Chandra, Atanu; Ray, Biman Kanti; Pandit, Alak
title: Treatment related fluctuation and response to intravenous immunoglobulin therapy in post COVID-19 Guillain-Barre syndrome()
date: 2021-08-13
journal: Diabetes Metab Syndr
DOI: 10.1016/j.dsx.2021.102246
sha: fd95b09651aca22ed89b4ddda285a1c27c95d11a
doc_id: 923349
cord_uid: hg16yw1l

Treatment related fluctuation (TRF) poses a special challenge in the treatment of Guillain-Barre syndrome (GBS). Many cases of GBS following COVID-19 infection have been reported in literature till date, but treatment related fluctuation (TRF) in post COVID-19 GBS has not been reported till date. We report a 35-year-old male patient who developed GBS following COVID-19 infection and had TRF after intravenous immunoglobulin (IV-IG) therapy. He required ventilator support but repeat IV-IG therapy led to complete recovery. Significant proximal muscle involvement, cranial nerve palsy, no antecedent diarrhea and absence of anti-GM1 antibodies are important predictors of TRF in GBS and need to be recognized early in the course of this illness. Early recognition of TRF and differentiating it from other forms of immune mediated neuropathy such as acute onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) are important for prognostication and management.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has wreaked havoc worldwide and has claimed innumerable lives till date. The clinical spectrum of this disease may range from mild self-limiting flu-like symptoms to the severe form of illness like severe pneumonia and acute respiratory distress syndrome (ARDS) with high morbidity and mortality. With better disease understanding and improved diagnostic techniques, a large number of cases are being detected with florid extrapulmonary manifestations and complications. [ 

In addition to the characteristic respiratory symptoms, reports are emerging of a wide-spectrum of neurological manifestations of COVID-19, which range from milder symptoms such as anosmia to severe complications such as stroke and encephalitis. Guillain-Barre syndrome (GBS)

is an immune-mediated neurological disorder, where the peripheral nerves are being affected by the immune system and there is a preceding history of an upper respiratory infection or gastroenteritis in most of the cases. [6] Different mechanisms have been proposed to explain the pathogenesis of GBS following COVID-19. The most accepted mechanism is the formation of antibodies against surface glycoproteins of the pathogen which may damage peripheral nerves due to a similar native protein structures (molecular mimicry). [7] Other proposed theories include hyperinflammation as a consequence of cytokine storm in patients with COVID-19. [8, 9] Since the outbreak of the pandemic, the incidence of GBS has increased. [10] There have been many reports describing the association between SARS-CoV-2 infection and GBS. [11, 12] Treatment deteriorates again after 8 weeks from the onset or when deterioration takes place for three times or more. According to a Dutch study, A-CIDP patients rarely develop cranial nerve dysfunction and very rarely need artificial ventilation. [13] TRF in this patient can occur due to prolonged immune response as the disease recurred after the therapeutic effect of immunoglobulin diminished off. The same study also reported almost one out of every ten GBS patients suffer from TRF and the disease almost never show secondary fluctuations beyond 8 weeks.

Many aspects of our patient acted as predictors of TRF. Romano et al mentioned that comorbidities increase chance of TRF but our patient had none. [14] Significant proximal muscle involvement, cranial nerve palsy, no antecedent diarrhoea and absence of anti-GM1 antibodies are important predictors of TRF in GBS, all of them were present in our patient. [9] TRF patients have non-favorable outcome compared to non TRF patients, which is not true in our case. [13] The important mechanisms of action of immunoglobulins are complement inactivation, antibody neutralization, inhibition of cytokines and saturation of Fc receptors on macrophages. [15] Early worsening after treatment followed by improvement on repeat treatment can be due to sustained production of antibodies and rebound immunological response. Many studies contradict this idea as antibody titres do not correlate with clinical worsening. [14] However, clinical scenario of our patient suggests the first explanation.

Worldwide many cases of post COVID-19 GBS are reported, however this is probably the first case reported with TRF and patient was successfully treated with reinstitution of immunoglobulin therapy; came out of ventilation and became ambulatory again.

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