medwireNews: A novel segmental facial brainstem sensory syndrome has been identified in three patients treated with pembrolizumab, thought to be caused by autoantibody binding to the surface of neurons.
The case study published as a research letter in JAMA Neurology includes a woman in her 60s treated for recurrent lung adenocarcinoma who presented with progressive symmetric facial paresthesia of her nose and forehead and hypoesthesia of her neck and shoulders.
A further two patients with cutaneous melanoma also experienced this side effect. Namely, a man in his 30s developed symmetric perioral paresthesia and numbness of the tongue, lower lip, and upper chin, while a man in his 70s initially experienced bilateral neuropathy and paresthesia of the forehead, scalp, nose, lips, ears, fingers and toes, followed by right-sided facial weakness after a further infusion.
All three individuals had an “unremarkable brain MRI with contrast,” write Sarosh Irani (University of Oxford, UK) and co-authors.
Pembrolizumab therapy was discontinued and patients were successfully treated with oral prednisolone 40 mg/day that was tapered off over a month, although the older man required a second 3-month course of corticosteroids after symptoms recurred.
Pembrolizumab was restarted in the woman but she experienced recurrent facial paresthesia.
Nevertheless, after 2 years of follow-up, all three patients were in “complete neurologic and oncologic remission,” the team says.
The researchers note that prospective monitoring of 120 other patients at the Oxford Autoimmune Neurology clinic between 2019 and 2020, including eight who experienced neurologic adverse events with nivolumab plus ipilimumab, found no further cases of what they describe as a “clinically distinctive, treatable, segmental facial brainstem sensory syndrome.”
Although serum screening for a panel of rheumatologic, neuronal, paraneoplastic, nodal, and paranodal autoantibodies was negative in the three affected patients, all had serum immunoglobulin G identified on the surface of rodent hippocampal neuron cultures – 1 year after treatment these autoantibodies had disappeared.
“Although their precise antigenic target was not investigated, their presence suggests [immune checkpoint inhibitor]-induced release of human autoantibodies may unveil intrinsic neuronal reactivities; excellent oncologic response is a feature of many patients with [immune-related adverse events],” Irani et al comment.
They conclude: “Future studies should aim to understand the immune-neurologic interactions of distinctive drug-induced complications.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group