Low specificity of voltage-gated calcium channel antibodies in Lambert–Eaton myasthenic syndrome: a call for caution

Abstract

As testing for neuronal antibodies become more readily available, the spectrum of conditions potentially associated with these autoantibodies has been widening. Voltage-gated calcium channel antibodies (VGCC-Ab) are no exception to this trend. The significance of an elevated VGCC-Ab titer beyond its original clinicopathological correlate, Lambert-Eaton myasthenic syndrome (LEMS) remains undetermined. We sought to determine the diagnostic significance of an elevated serum VGCC-Ab titer in a large single-center cohort of 100 patients. The majority of patients (58%) with elevated VGCC-Ab levels lacked an inflammatory or autoimmune etiology of their neurologic diagnosis. Only six cases (6%) of LEMS and two cases (2%) of SCLC (without LEMS) were identified. No significant differences in antibody titers were seen between the autoimmune and non-autoimmune groups. These findings support the notions that: (a) elevated VGCC-Ab titers without clinical correlation must be interpreted with caution, and (b) the clinical and electrodiagnostic criteria for LEMS should remain the mainstay in the diagnosis of LEMS.

Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

“…P/Q type VGCC antibodies have been reported to be very sensitive and specific for the diagnosis of LEMS [16,17], although low titers could be found also in controls, in patients with various types of cancers as well as in patients with amyotrophic lateral sclerosis [16,57]. However, a recent study observed the presence of these antibodies in a high proportion of patients without a neurological autoimmune or inflammatory etiology, with no difference in antibody titers between the autoimmune and the not-autoimmune groups [58], confirming that the P/Q type VGCC antibodies are not diagnostic in the absence of clinical and electrophysiologic features of LEMS. No correlation has been found between antibody titers and clinical features or outcome, although antibody levels might decrease after immunosuppressive treatment [59,60].…”

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Presenting as Recurrent and Migrating Focal Cortical Encephalitis

“…13 Elevated voltage-gated calcium channel antibodies have frequently been found in both healthy controls and non-autoimmune conditions, including neurodegenerative conditions, and the voltage-gated calcium channel antibody positivity has been hypothesized to be a downstream effect due to neuronal injury following a non-specific immune activation due to a primary underlying disease process. 14,15 The co-existence of MOG antibodies and voltage-gated calcium channel antibodies is not well-documented; however because MOG antibodies have been shown to cause similar presentations in adults without the co-existence of voltage-gated calcium channel antibodies, the N-type calcium channel and GAD65 antibodies likely do not represent significant findings in our patient.…”

Autoimmune Channelopathies at Neuromuscular Junction

“…Interestingly, recent researches reported that antibodies against VGCC were detected not only in other autoimmune diseases, such as MG, but also in healthy people, which questioned the specificity of antibodies against VGCC for LEMS diagnosis. Di Lorenzo found that antibodies against P/Q-type VGCC had a diagnostic sensitivity of 88.89% and specificity of 36.17% (58). Zalewski also reported that antibodies against P/Q-type VGCC have a compromised specificity on LEMS diagnosis (59).…”