PGY5 clinical fellow Baylor College of Medicine Houston, Texas, United States
Objective: Elevation of GAD65 antibodies (GAD65 Ab) is commonly seen in patients with type 1 diabetes (T1DM). High GAD65 Ab titers (>20 nmol/L) are associated with autoimmune neurologic syndromes. With increased use of checkpoint inhibitors (CPI) for cancer treatment, and presence of GAD65 Ab positivity in 45% of patients with checkpoint inhibitor diabetes (CPIDM), there is paucity of data in published literature on the correlation of GAD65 Ab positivity and neurologic symptoms in this patient population.
Methods: In this study, we conducted a retrospective chart review of patients with CPIDM and GAD65 Ab positivity (n=40) to determine frequency of neurologic symptoms in this population. We excluded patients with brain metastases (n=6), due to challenge of distinguishing etiology of neurologic symptoms in this setting.
Results: Of the 34 patients remaining with CPIDM and positive GAD65 Ab, 97% had CPI exposure within a year of GAD65 Ab positivity. 91% (n=31) had GAD65 Ab titers ranging from 0.03 to 15.3 nmol/L, and 77% (n=24) had a myriad of mild neurologic symptoms, with weakness (54%), limb paresthesia (42%), and lightheadedness (29%) being the most common, and not warranting further investigation. More than half (58%, n=18) of these patients with low GAD65 Ab titers had a prior diagnosis of diabetes, and 61% presented with overt ketoacidosis at the time of CPIDM diagnosis.
Three (8%) patients had significant GAD65 Ab elevation >20 nmol/L. The first patient had a history of T2DM and GAD65 Ab titer of 381 nmol/L, but only reported dizziness. The remaining 2 patients did not have past history of diabetes and had polyneuropathy and mild optic neuritis with GAD65 Ab titer of 38.4 nmol/L, and no neurologic symptoms with GAD65 titer of 28.1 nmol/L, respectively.
Out of the 34 patients, only 3 had pertinent neurologic symptoms: one was noted to have ataxia, apraxia, dystonia, and visual hallucinations, with positive CSF GAD65 Ab as well as severe cyanocobalamin deficiency. Another patient had overt clinical myasthenia with positive ACh-binding antibody; patient symptoms not attributable to GAD65 Ab positivity. Both of these patients had fairly low GAD65 Ab titers, 0.09 and 1.28 nmol/L, respectively. One patient was deemed by neurology to have GAD65 Ab-related aseptic meningitis had a GAD65 Ab titer of 0.25 nmol/L.
Discussion/Conclusion: Neurologic symptoms have been reported in patients with classic T1DM and elevated GAD65 Ab titers (>20 nmol/L). In this descriptive study, we noted that in patients with CPIDM, the presentation of neurological symptoms do not correlate with GAD65 Ab titer. CPI treatment can cause neurologic syndromes that are not associated with high GAD65 Ab titers. Our study suggests that GAD65 Ab titers >20 nmol/L in patients with CPIDM are not consistently associated with neurological symptoms as those seen with classic T1DM.