Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy that accounts for approximately 100,000 new cases annually worldwide. In most patients, the acute onset of neurological symptoms is preceded by an infectious event, followed by progressive limb weakness, which may last up to 4 weeks before reaching a plateau. The symptomatic spectrum is broad and can be divided into different subtypes which are associated with specific anti-ganglioside antibodies.1
IgG-type anti-GM2 ganglioside antibody syndrome is a very low prevalence subtype of GBS, typically presenting with cranial neuropathies. Although the association of classical variant GBS with SARS-CoV-2 infection has been described, no cases of anti-GM2 ganglioside syndrome associated with previous SARS-CoV-2 infection have been reported in the scientific literature.2
A 31-year-old male, with no medical history of interest, who was admitted for a 1-year history of fluctuating vertiginous syndrome associated within the last month and a half with binocular diplopia. What was most striking during history-taking was the onset of symptoms after the SARS-CoV-2 vaccination with AztraZeneca and the perpetuation and worsening of symptoms after the second vaccination and after oligosymptomatic o subclinical SARS-CoV-2 infection, with cough, odynophagia and self-limiting fever, some 4 weeks before the onset of diplopia.
On examination there was non-fatigable binocular diplopia, in maximal levoversion and dextroversion, without obvious restriction but corresponding with paralysis of both medial rectus muscles in cover test, with minimal horizontal rotatory nystagmus in maximal levoversion. Normo-reactive isochoric pupils. Rest of cranial nerves preserved. Normal stretch reflexes, no ataxia, with normal gait and negative Romberg. Absence of paresis and impaired sensation in all 4 limbs. No signs of meningeal irritation. The rest of the examination by organs and systems was normal.
Routine blood tests, including CBC, renal function, liver function, acute phase reactants (glomerular sedimentation rate and C-reactive protein), blood glucose and coagulation were within normal limits. CT scan and brain MRI were normal. A lumbar puncture was performed without cell detection, with normal protein levels (36mg/dl) and normal opening pressure (20cmH2O). Electroencephalogram and electromyogram without abnormalities. Among the autoimmunity tests requested, antinuclear antibodies, rheumatoid factor and myasthenia gravis antibodies (anti-RaCh and anti-Musk) were negative, with normal complement levels.
Because the symptoms were consistent with multiple cranial neuropathy (oculomotor and vestibular involvement) with a probable dysimmune mechanism, given the clinical worsening after an infectious event, anti-ganglioside antibodies were requested, and the anti-GM2 IgG variant was positive. Treatment was started with 125mg methylprednisolone boluses for 5 days with subsequent de-escalation to oral therapy. The improvement was spectacular, with complete correction of the diplopia and associated vestibular symptoms.
IgG-type anti-GM2 ganglioside antibody syndrome is an atypical and extremely rare variant of GBS. The prevalence of anti-GM2 antibodies comprises less than 10% of the different anti-ganglioside antibodies observed, and has been shown to be associated with mycoplasma, herpes simplex virus and cytomegalovirus. These antibodies can induce neuronal damage through complement-mediated cytotoxicity. IgM-positive patients appear to manifest more heterogeneous symptomatology, unlike IgG-positive patients, who characteristically present with multiple cranial neuropathies, predominantly oculomotor and vestibular involvement. The forming mechanism of these autoantibodies appears to be based on the theory of molecular mimicry, which suggests the similarity between epitopes of different pathogens and ganglioside oligosaccharide structures, contributing to the development of immune system autoreactivity.2
We obtained a score of 6 when applying a Naranjo causality algorithm in our case, suggesting a high probability of a causal relationship with SARS-CoV-2.
Although COVID-19 is predominantly a respiratory disease, it can affect multiple organs, including the nervous system.3 The association between COVID-19 infection and GBS is described in the literature, including less common variants such as Miller-Fisher syndrome and some case reports of cranial polyneuritis, although GM2 antibodies have not been detected. The pathogenic mechanism in these cases appears to be immune-mediated, given the occasional presence of antibodies and the absence of SARS-CoV-2 detection in cerebrospinal fluid.4,5
The aim of this case report is to highlight the characteristics of this syndrome, its dysimmune pathophysiological basis and its probable relationship with SARS-CoV-2 infection. Although isolated cases of polyneuritis cranialis have been observed after infection with COVID-19, this is the first documented case associated with anti-GM2 ganglioside antibodies.
(The literature research was carried out using the PUBMED database, using the descriptors “anti-GM2-Ganglioside-Antibody”, “covid19”, “polyneuritis cranialis”, “guillain barré syndrome”. The search was conducted as of 23/10/2022. The years covered were 2012–2022).
