Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition

Abstract

The concept of antibody mediated CNS disorders is relatively recent. The classical CNS paraneoplastic neurological syndromes are thought to be T cell mediated, and the onconeural antibodies merely biomarkers for the presence of the tumour. Thus it was thought that antibodies rarely, if ever, cause CNS disease. Over the past 10 years, identification of autoimmune forms of encephalitis with antibodies against neuronal surface antigens, particularly the voltage gated potassium channel complex proteins or the glutamate N-methyl-D-aspartate receptor, have shown that CNS disorders, often without associated tumours, can be antibody mediated and benefit from immunomodulatory therapies. The clinical spectrum of these diseases is not yet fully explored, there may be others yet to be discovered and some types of more common disorders (eg, epilepsy or psychosis) may prove to have an autoimmune basis. Here, the known conditions associated with neuronal surface antibodies are briefly reviewed, some general aspects of these syndromes are considered and guidelines that could help in the recognition of further disorders are suggested.

Clinical experience of seropositive ganglionic acetylcholine receptor antibody in a tertiary neurology referral center

“…Although our data suggest an overall increased risk of current or previously existing malignancy in individuals with positive gAChR‐Ab irrespective of their clinical syndrome, the presence of gAChR‐Ab in most patients is not a marker of malignancy. This is consistent with the previous impression that the presence of neuronal surface antibodies is not a strong predictor of paraneoplastic autoimmunity …”

Clinical experience of seropositive ganglionic acetylcholine receptor antibody in a tertiary neurology referral center

“…Although our data suggest an overall increased risk of current or previously existing malignancy in individuals with positive gAChR‐Ab irrespective of their clinical syndrome, the presence of gAChR‐Ab in most patients is not a marker of malignancy. This is consistent with the previous impression that the presence of neuronal surface antibodies is not a strong predictor of paraneoplastic autoimmunity …”

Clinical variables that help in predicting the presence of autoantibodies in patients with acute encephalitis

“…The clinical and paraclinical characteristics observed in our patients with positive results for the analyzed antibodies are similar to those described in the literature [33,9,10]. In our study, NMDAR encephalitis affected predominantly young individuals, as described by other authors [10], with a predominance of females (2:1), which is lower compared to other case series [31,34].…”

Investigation of neuronal autoantibodies in two different focal epilepsy syndromes

“…Furthermore, subcortical bifrontal and left parietal hyperintensities were reported in one 9‐year‐old encephalitis case with VGKC antibodies . The present study, however, extends previous anecdotal observations and suggests that WMCs seem to be a possible marker for the presence of autoantibodies in epilepsy patients and should also be included in the indication list for search of neuronal antibodies . This association may partly be related to the coexistence of patients with SLE, migraine, and HT, since all of these disorders are known to cause WMCs .…”

Clinical experience of seropositive ganglionic acetylcholine receptor antibody in a tertiary neurology referral center

“…Although our data suggest an overall increased risk of current or previously existing malignancy in individuals with positive gAChR‐Ab irrespective of their clinical syndrome, the presence of gAChR‐Ab in most patients is not a marker of malignancy. This is consistent with the previous impression that the presence of neuronal surface antibodies is not a strong predictor of paraneoplastic autoimmunity …”

Clinical variables that help in predicting the presence of autoantibodies in patients with acute encephalitis

“…The clinical and paraclinical characteristics observed in our patients with positive results for the analyzed antibodies are similar to those described in the literature [33,9,10]. In our study, NMDAR encephalitis affected predominantly young individuals, as described by other authors [10], with a predominance of females (2:1), which is lower compared to other case series [31,34].…”

Investigation of neuronal autoantibodies in two different focal epilepsy syndromes

“…Furthermore, subcortical bifrontal and left parietal hyperintensities were reported in one 9‐year‐old encephalitis case with VGKC antibodies . The present study, however, extends previous anecdotal observations and suggests that WMCs seem to be a possible marker for the presence of autoantibodies in epilepsy patients and should also be included in the indication list for search of neuronal antibodies . This association may partly be related to the coexistence of patients with SLE, migraine, and HT, since all of these disorders are known to cause WMCs .…”

Clinical experience of seropositive ganglionic acetylcholine receptor antibody in a tertiary neurology referral center

“…Although our data suggest an overall increased risk of current or previously existing malignancy in individuals with positive gAChR‐Ab irrespective of their clinical syndrome, the presence of gAChR‐Ab in most patients is not a marker of malignancy. This is consistent with the previous impression that the presence of neuronal surface antibodies is not a strong predictor of paraneoplastic autoimmunity …”

Clinical variables that help in predicting the presence of autoantibodies in patients with acute encephalitis

“…The clinical and paraclinical characteristics observed in our patients with positive results for the analyzed antibodies are similar to those described in the literature [33,9,10]. In our study, NMDAR encephalitis affected predominantly young individuals, as described by other authors [10], with a predominance of females (2:1), which is lower compared to other case series [31,34].…”

Investigation of neuronal autoantibodies in two different focal epilepsy syndromes

“…Furthermore, subcortical bifrontal and left parietal hyperintensities were reported in one 9‐year‐old encephalitis case with VGKC antibodies . The present study, however, extends previous anecdotal observations and suggests that WMCs seem to be a possible marker for the presence of autoantibodies in epilepsy patients and should also be included in the indication list for search of neuronal antibodies . This association may partly be related to the coexistence of patients with SLE, migraine, and HT, since all of these disorders are known to cause WMCs .…”