TABLE 2.

Clinical presentation of the main ICI-related central neurological syndromes

	Encephalitis (Vogrig et al., 2019a; Dubey et al., 2018; Dalmau et al., 2017a; Wesley and Ferguson, 2019; Vogrig et al., 2019b; Simard et al., 2020; Vogrig et al., 2019c; Kayser et al., 2010; Shams’ili et al., 2003; Muñiz-Castrillo et al., 2020; Vogrig et al., 2020b; Dalmau et al., 2017b; Touat et al., 2017a; Johnson et al., 2019a; Stuby et al., 2020; Graus et al., 2016; Fujiwara et al., 2017; Touat et al., 2017b; Velasco et al., 2021)	Vasculitis (Calabrese et al., 1992; Salvarani et al., 2007; Salvarani et al., 2008; Hajj-Ali et al., 2011; Park and Ranganathan, 2011; Giannini et al., 2012; Berlit and Kraemer, 2014; Thom et al., 2016; Daxini et al., 2018)	Meningitis (Larkin et al., 2017; Daxini et al., 2018; Fellner et al., 2018; Laserna et al., 2018; Johnson et al., 2019a; Johnson et al., 2019b)	Myelitis (Altrocchi, 1963; Lipton and Teasdall, 1973; Christensen et al., 1990; Misra et al., 1996; Transverse Myelitis Conso, 2002; Defresne et al., 2003; de Seze et al., 2005; Pidcock et al., 2007; Cabrera-Gómez et al., 2009; Mader et al., 2010; Hwang et al., 2018; Cuzzubbo et al., 2020; Picca et al., 2021)	MS (Pohl et al., 2004; Hauser et al., 2008; Filippi et al., 2016; Gerdes et al., 2016; Garcia et al., 2019; Oliveira et al., 2020)	CND (Weerasinghe and Lueck, 2016; Yost et al., 2017; Dubey et al., 2019; Vogrig et al., 2021)
Incidence (% patients treated with ICIs)	0.16%	<0.01%	0.13%	<0.01%	0.03%	–
Clinical course	Psychiatric symptoms, memory deficits, motor neuron syndrome	Headache, altered cognition, focal deficits	Headache, fever, neck stiffness, confusion	Sensory dysfunction, dysautonomia	Sensory alterations, cerebellar dysfunction, fatigue, dysautonomia	Cranial nerve palsy (VII > VIII > II > rest)
Median delay of symptoms	65 days	3 months	9 days	4 months	Variable	3 months
Auto-Abs	Anti-Ma2 (15%)	–	–	Anti-AQP4 (18%)	–	–
	Anti-Hu (8%)
	Anti-GAD (5%)
	Anti-NMDAR (3%)
	Anti-CASPR2 (1.7%)
CSF	Pleocytosis, high protein levels	Pleocytosis, high protein levels	Pleocytosis, high protein levels	Pleocytosis, high levels of IgG, IL-6 and 14-3-3 protein	Pleocytosis, oligoclonal IgG	Pleocytosis
	Oligoclonal bands	High levels of IL-17
MRI	T2 and FLAIR hyperintense signals in temporal lobes and/or cerebellum	T2 and FLAIR hyperintense signals	No alterations	T2 signal abnormality co-related to sensory level	T2 and FLAIR hyperintense disperse focal lesions in brain white matter	Cranial nerve enhancement (25%)
		Hemorrhage or ischemic damage		Occasional T1 hypointense lesions

MS: multiple sclerosis; CND: cranial nerve disorders. CSF: cerebrospinal fluid. MRI: magnetic resonance image.