Episodic Bradycardia as Neurocardiac Prodrome to Voltage-Gated Potassium Channel Complex/Leucine-Rich, Glioma Inactivated 1 Antibody Encephalitis

Abstract

oltage-gated potassium channel complex antibody (VGKCc-Ab) encephalitis is characterized by rapidonset dementia, seizures, and hyponatremia. 1,2 The leucine-rich, glioma inactivated 1 (LGI1) protein, part of the VGKCcomplex, is the established antigenic target in most cases of this antibody-mediated limbic syndrome. 3,4 We describe 3 patients with VGKCc/LGI1-Ab encephalitis who developed episodic bradycardia requiring pacemaker implantation prior to the onset of encephalopathy. As LGI1 is widely expressed throughout brain but not cardiac tissue 4 and as cardiac conduction can be modulated by cortical autonomic centers, 5 we propose that the antibody-associated encephalitis generates episodic bradycardia early within the disease process.

More evidence of a neurocardiac prodrome in anti-LGI1 encephalitis

“…In accordance with the previously described case reports from Naasan et al [5], time from cardiac symptoms to onset of encephalopathy and hyponatremia known to be temporally associated with LGI1 encephalitis, in our patient was approximately two months. The reason for this novel prodrome is still unknown, but as suggested it is likely due to focal epileptic activity secondary to encephalitis or neuroinflammation in the adjacent insular and temporal regions [5]. Since the expression of LGI1 is very low in heart compared with brain [6], a direct effect of pathogenic antibodies on the heart seems less likely.…”

“…In some patients, brief and frequent faciobrachial dystonic seizures (FBDS) may precede other features, thereby allowing therapy to prevent the development of neuropsychiatric manifestations [2][3][4]. Recently, three patients with anti-LGI1 encephalitis preceded by episodic bradycardia requiring pacemaker implantation were described [5]. Lending further support to this neurocardiac prodromal syndrome, we report an additional case of anti-LGI1 encephalitis presenting with severe bradycardia requiring acute pacemaker implantation.…”

High prevalence of electrocardiac abnormalities in anti-CASPR2 antibody-associated disease

“…Another example of peripheral autonomous dysfunction in patient with MoS is hyperhydrosis, which is considered to be caused by hyperexcitability of peripheral sudomotor nerves. This is different from bradycardia in LGI1 Ab-associated encephalitis which is probably caused by central cardiac autonomous dysfunction involving insular and temporal lobe as well as cortical regions,3 and arrhythmia in anti-NMDA receptor encephalitis with perhaps both peripheral and central mediation. These may indicate high prevalence of electrocardiac involvement in autoimmune encephalitis.…”

“…Serious neurocardiac events have been reported in patients with LGI1 Ab-associated encephalitis as a distinctive prodrome which led to pacemaker implantations,3 whereas arrhythmia and its prognostic impact were poorly addressed in the clinical evaluation of CASPR2 Ab-positive patients. Tachycardia and bradycardia were previously reported in 28.6% (4/14) and 3.9% (2/51) patients with anti-CASPR2 Abs,2 4 respectively.…”

Seizures and Epilepsies due to Channelopathies and Neurotransmitter Receptor Dysfunction: A Parallel between Genetic and Immune Aspects

“…FBDS seems to be related with LGI1 antibodies, since no FBDS was reported in 5 Korean patients with CASPR2 antibodies [Sunwoo et al, 2015]. Even though ictal and peri-ictal dysautonomic features such as tachychardia, blood pressure abnormalities, or hypersalivation are primarily observed in anti-NMDAR encephalitis (see above, Part 1) or Caspr2 encephalitis [Baysal-Kirac et al, 2016], pilomotor seizures [Rocamora et al, 2014] and bradycardia [Naasan et al, 2014] were respectively described in 3/5 and in 3/14 patients in association with LGI1 antibodies.…”