Calcium channel autoimmunity: Cerebellar ataxia and lambert‐eaton syndrome coexisting

Abstract

Calcium channel autoimmunity should be considered in patients with coexisting cerebellar ataxia and myasthenic weakness. Affected patients may survive small-cell carcinoma or have immunotherapy-responsive neurological symptoms. Muscle Nerve, 2018.

Nivolumab‐associated Lambert‐Eaton myasthenic syndrome and cerebellar dysfunction in a patient with a neuroendocrine tumor

“…Although the presenting cerebellar symptoms likely resulted from the cerebellar metastasis, the cerebellar symptoms after nivolumab initiation were likely a neurologic irAE, as previously reported. 4,5 VGCC autoantibody-positive LEMS and SCD have been reported to co-occur, 6 and we postulate that nivolumab triggered both VGCC-mediated paraneoplastic diseases in this patient.…”

Lambert—Eaton myasthenic syndrome and cerebellar ataxia: is Response to immunotherapy a clue to pathogenesis?

“…19 As may be expected from a disorder in which the antigenic target is expressed on the neuronal surface membrane, the response to immunotherapy in patients with ataxia and mGluR1 antibodies is favorable. 20 This clinical series of patients with LEMS and ataxia described by Zalewski and colleagues, 12 the largest to date, further establishes the link between LEMS, ataxia and VGCC antibodies, highlighting the importance of screening for lung tumors in patients with subacute ataxia who harbor VGCC antibodies. Where the neurologic symptoms are mediated by antibodies to a neuronal surface antigen (VGCC), it is important to initiate immunotherapies as soon as possible to achieve a favorable clinical outcome, particularly in terms of the ataxia.…”

“…In this issue of the Journal, Zalewski and colleagues describe the clinical presentations and treatment outcomes in 17 patients with LEMS and PCD in a retrospective single‐center study . LEMS symptoms appeared first in almost half of the patients (8 of 17, 47%): ataxic symptoms first in 4 patients and then simultaneous LEMS and ataxia in 4.…”

“…It seems less likely that VGCC antibody access to the central nervous system across the blood–brain barrier is limited to patients with PCD rather than LEMS. It is not clear why only a small fraction (thought to be < 10%) of patients with LEMS and P/Q‐type VGCC antibodies develop ataxia. It is possible that ataxia may not manifest clinically in such patients unless there has been significant loss of functional VGCCs.…”

Autoimmunity to voltage‐gated calcium channels

“…29 From overseas, it can be seen that there are cases of PCD and cerebellar ataxia associated with LEMS that improve with antitumor and immunotherapy. 34 Furthermore, cases of P/Q-VGCCs antibody-positive cerebellar ataxia in which immunotherapy was effective have also been reported from overseas. [35][36][37] The above clinical evidence supports the hypothesis that the cerebellar manifestations of PCD-LEMS are caused by P/Q-type VGCC antibodies, as is the neuromuscular junction in LEMS.…”