From the Guidelines
Checkpoint inhibitor therapy can cause severe neurological side effects, and management should be guided by the severity of symptoms, with mild symptoms (grade 1) requiring monitoring, moderate symptoms (grade 2) necessitating temporary suspension of therapy and corticosteroids, and severe symptoms (grade 3-4) requiring permanent discontinuation of therapy and high-dose corticosteroids, as recommended by the American Society of Clinical Oncology clinical practice guideline 1.
Neurological Side Effects of Checkpoint Inhibitors
Checkpoint inhibitors have been associated with a range of neurological side effects, including headache, peripheral neuropathy, myasthenia gravis, Guillain-Barré syndrome, encephalitis, transverse myelitis, and aseptic meningitis, with an overall incidence of neurologic irAEs reported to be 3.8% in patients receiving anti–CTLA-4 antibodies, 6.1% in patients receiving anti–PD-1 antibodies, and 12.0% in patients receiving a combination of both 1.
Management of Neurological Side Effects
Management of these side effects depends on the severity of symptoms, with the following approaches recommended:
- For mild symptoms (grade 1), checkpoint inhibitor therapy may be continued under close observation 1.
- For moderate symptoms (grade 2), checkpoint inhibitor therapy should be held until the nature of the irAE and symptom progression is defined, and a corticosteroid equivalent of methylprednisolone 1 to 4 mg/kg should be started 1.
- For severe symptoms (grade 3-4), immunotherapy should be discontinued, and symptom control may require escalation of corticosteroid therapy to pulse-dose methylprednisolone (1 g daily for 5 days) in addition to IVIG, or plasma exchange (PEX) 1.
Importance of Neurological Consultation
Neurological consultation is essential for proper diagnosis and management of these side effects, as it can help determine the type and severity of neurologic impairment and guide selection and interpretation of further neurologic tests and management 1.
From the Research
Neurological Side Effects of Checkpoint Inhibitors
- Checkpoint inhibitors are associated with a wide spectrum of neurologic immune-related adverse events (irAEs), including meningo-encephalitis, myasthenia gravis, and various neuropathies 2.
- The most frequently reported neurological side effects are myopathies, neuropathies, diseases of the neuromuscular endplates, and encephalitides 3.
- Encephalitides and myopathies with accompanying myocarditis are associated with the highest morbidity and mortality 3.
- Symptoms suggestive of encephalitis, myasthenia-gravis, or an acute polyradiculopathy such as Guillain-Barre Syndrome (GBS) in patients exposed to these agents warrant immediate attention with a low threshold for hospitalization 2.
Treatment and Outcomes
- Treatment of neurological side effects consists of holding the immune checkpoint inhibitor, administration of corticosteroids, and other immunomodulatory agents as needed 4.
- Early steroid treatment increases the probability of a complete remission of neurological symptoms 3.
- The outcomes are generally favorable; however, rarely severe events can lead to significant morbidity and even mortality 4.
- Myasthenia gravis induced by immune checkpoint inhibitors is a rare immune-related adverse event that can be life-threatening and requires rapid treatment 5.
Clinical Guidelines
- All providers who care for patients with cancer should be made aware of common neurologic irAEs and able to recognize when prompt evaluation and consultation with appropriate specialists are indicated 2.
- Clinical practice guidelines recommend rapid recognition and treatment of neurological side effects, including immunosuppressive therapy 6.
- Further studies are needed to better describe these neurological side effects and to implement clinical guidelines 6.