# Myasthenia-Like Presentations Following PD-1 Inhibitors: CD8+ Myositis, Myasthenia, or Both?

## TL;DR

This paper explores neuromuscular complications caused by PD-1 inhibitors, focusing on myasthenia-like symptoms and the role of CD8+ myositis.

## Contribution

The study identifies CD8+ myositis as a primary driver of ICI-related neuromuscular syndromes, challenging traditional antibody-based diagnostic approaches.

## Key findings

- Five patients developed acute neuromuscular symptoms after PD-1 therapy, with myasthenia-like features.
- CD8+ inflammatory infiltration in muscle biopsies suggests myositis as a key mechanism.
- Pyridostigmine responsiveness and fluctuating symptoms support coexisting myasthenia despite seronegative results.

## Abstract

Immune checkpoint inhibitors (ICIs) can trigger immune-mediated neuromuscular complications, where myositis and myasthenia frequently overlap, creating major diagnostic and therapeutic challenges.

We retrospectively analyzed five patients who developed acute neuromuscular symptoms after anti-programmed death-1 (PD-1) therapy. Clinical data, laboratory findings, electromyography, muscle biopsy results, treatments, and outcomes were reviewed.

All patients presented with varying combinations of oculobulbar weakness, dysphagia, limb weakness, and respiratory failure. Despite the myasthenia-like presentation, anti-acetylcholine receptor and anti-muscle-specific kinase antibodies were negative in four of five patients. In contrast, electromyography predominantly revealed subacute myogenic findings, with one patient exhibiting a neurogenic pattern. Muscle biopsies demonstrated CD8⁺-predominant inflammatory infiltration. The diagnosis of coexisting myasthenia was supported based on fluctuating symptoms and ventilator requirements, such as tidal volume and inspiratory pressure, as well as pyridostigmine responsiveness, rather than serologic findings. Most patients required immunosuppressive therapy, including corticosteroids, intravenous immunoglobulin, and, in some cases, cardiac or respiratory support.

ICI-related neuromuscular syndromes frequently present with myasthenia-like symptoms but are primarily driven by CD8⁺-mediated myositis rather than classical antibody-mediated pathology. Fluctuating respiratory or bulbar symptoms and response to pyridostigmine can guide differentiation between isolated myositis and coexisting myasthenia, which is crucial for optimizing ventilatory management. Therefore, a diagnostic trial of pyridostigmine is recommended in cases of ICI-related respiratory or bulbar deterioration, even in seronegative patients, as it may help clarify the underlying mechanism and guide timely therapeutic decisions.