Inhibitors and their Neurological Side effects

Program cell death 1 (PD-1) receptors are trans-membrane proteins on the surfaces of T-cells that interact with program death-ligands (PD-L) on somatic cells. These interactions act as immune checkpoint regulators and play an important role in the development of auto-immunity and tumor development. Tumor cells often express PD-L to evade immune system recognition. PD-1 inhibitors by blocking PD-1 receptor allow immune system to mount a response against tumor cells. PD-1 inhibitors have been used in treatment of advanced cancers like non-small cell lung cancer, metastatic melanomas, solid tumors and head and neck cancers. Due to PD-1 inhibitors blunting of self-regulating immune responses, several immune-related adverse events (irAEs) have been linked with their usage. As the practice of immune checkpoint inhibitors become more predominant, so do immune-related adverse events associated with their implementation. The immune-related adverse events linked with this class of drugs are commonly seen and are classified as trivial adverse events. Reported neurologic adverse effects include dysphasia, tremors, ataxia, parestheisias, paresis and more uncommon cases of myasthenia gravis like syndrome.These are simply treated with IVIG and steroids if identification of symptomatology and treatment are promptly executed. Diagnosis is further supported by CSF findings of albuminocytologic dissociation anti-Ach, and MUSK antibodies. Infectious workup must be obtained and paraneoplastic syndromes must be ruled out in all cases.However, neurologic immune-related adverse events are less comprehended and have been seldom cited in the medical literature, thus representing a challenge for clinicians. We hereby present three cases of patients treated with PD-1 inhibitors and developed myasthenia gravis-like symptoms and immune-therapy induced Guillain-Barré syndrome.

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Discussion

PD-1 inhibitors can cause various neurological complications. Neurological side effects include tremors, dysarthria, ataxia, paresis and paresthesias’. We reported 3 cases with a novel complication of PD-1 inhibitor therapy.

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