Table 2.
Laboratorial, electrophysiological, and imaging examinations of ICI–related neurological adverse events in NSCLC.
| Reference | Age/sex | Neurological adverse events | EEG/EMG/SFEMG | NCS | RNS | Image examination | Antibodies of paraneoplastic neurological syndrome/serum laboratory data | CSF test | Co-occurring non-neurological irAEs |
|---|---|---|---|---|---|---|---|---|---|
| Abe et al 10 | 58/M | Akathisia | NR | NR | NR | Brian MRI: negative | Negative for all | Negative | NO |
| Richard et al 11 | 74/M | Encephalitis | EEG: mild slowing, no evidence of seizure activity | NR | NR | Chest X ray: negative MRI: not conducted |
Not conducted | Negative | Euthyroid sick syndrome |
| Nakatani et al 12 | 73/F | Lambert-Eaton myasthenic syndrome | NR | Low-amplitude CMAP | Waning phenomenon in 3 Hz RNS, waxing phenomenon in 10 and 20 Hz RNS | Chest CT: right hilar lymphadenopathy, primary tumor in the right lower lobe | AChRAbs: negative, anti-P/Q-type VGCC antibody: positive, anti-thyroglobulin antibody: positive | Negative | Hypothyroidism |
| Schneider et al 13 | 78/M | Autoimmune encephalitis | EEG: moderate background slowing, focal delta slowing over the left temporal region | NR | NR | CT: negative Brain MRI: negative |
Negative for all | Reduced level of glucose, elevated lactate: 4.1 mmol/L, protein level: 1027 mg/L, pleocytosis: 16 lymphocytes/µL | NO |
| Leitinger et al 14 | 67/F | Necrotizing encephalopathy | EEG: rule out complex-partial status epilepticus, moderate diffuse slowing | NR | NR | MRI: edematous disseminated lesions | Negative for all | Inflammatory CSF findings and increased IgG level | NO |
| Jacob et al 15 | 68/F | GBS | NR | NR | NR | Brain CT: partial response Spine MRI: negative |
NR | CSF: no nucleated cells, normal glucose, elevated protein level, albuminocytological dissociation (consistent with a diagnosis of GBS) | NO |
| Läubli et al 16 | 53/M | Cerebral vasculitis/necrotizing encephalitis | NR | NR | NR | Brain MRI: new parietotemporal lesion in proximity of the formerly irradiated masses | Antibodies against neuronal antigens: negative, anti-SSA/Ro and anti-SSB/La antibodies: positive | NR | NO |
| Fukumoto et al 17 | 66/M | Acute demyelinating polyneuropathy | NR | Decreased distal sensory nerve action potentials on median and ulnar nerves, prolonged distal latency | NR | NR | IgM antibodies to GM2 and GalNAc-GD1a: positive, CK: 36 IU/L | CSF: 4 leucocytes/μL, protein level: 339 mg/dL | NO |
| Tan et al 18 | 45/M | Myasthenic crisis and myositis | NR | NR | No decremental response | Brain MRI: no evidence of stroke or metastasis | AChRAbs: 2.00 nmol/L, transaminitis, elevated muscle enzymes | NR | NO |
| Chen 19 | 57/M | Myasthenia gravis, myositis, and polyneuropathy | EMG: active denervation and myopathic changes in sample muscles, SFEMG over right orbicularis oculi: mean consecutive difference of 74 µs | Sensorimotor polyneuropathy of axonal degeneration | No decremental response | NR | AChRAbs: 0.70 nmol/L, CK: 2682 U/L | Slightly lower protein level at 13 mg/dL | NO |
| Chen et al 20 | 65/M | Myasthenia gravis | EMG: negative | Polyneuropathy of median, ulnar, peroneal, tibial, and sural nerves | Negative | Brain MRI: negative | AChRAbs: not detected, CK: 2216 U/L, AST: 153 U/L, ALT: 110 U/L, LDH: 484 U/L, troponin-I: 2.62 ng/mL | NR | NO |
| Ong et al 21 | 68/M | Guillain-Barré-like syndrome | NR | Prolonged tibial motor distal latency, partial conduction block in peroneal motor nerves, sparing of the sural sensory response | NR | Spine MRI: degenerative changes | Paraneoplastic autoantibodies: negative | NR | NO |
| Polat et al 22 | 65/M | Myasthenia gravis | NR | Normal after the treatment of pyridostigmine | Normal after the treatment of pyridostigmine | MRI: negative Chest X ray: negative |
AChRAbs and anti-MUSK: negative after myasthenia gravis disappear | NR | NO |
| Sciacca et al 23 | 81/M | Myasthenia gravis | SFEMG over orbicularis oculi: abnormal (mean jitter, 36 µs; 15% pairs with abnormal jitter) | NR | Negative | NR | AChRAbs: 0.40 nmol/L, ALT: 296 U/L, AST: 325 U/L | NR | NO |
| Hussein et al 24 | 47/F | PRES | NR | NR | NR | MRI: PRES | NR | NR | NO |
| Hibino et al 25 | 83/M | Myasthenia gravis with myositis | NR | NR | Negative | Brain MRI and abdominal CT: negative | Autoimmune antibodies: negative, CK:4361 IU/L, aldolase: 134.8 IU/L, myoglobin: 4572.0 ng/mL, LDH: 580 IU/L, AST: 269 IU/L, ALT: 222 IU/L | NR | Myositis and hepatitis. |
| Mori et al 26 | 64/M | Optic neuritis | NR | NR | NR | MRI: high-intensity lesion in left optic nerve | NR | Protein level: 69 mg/dL | Hypopituitarism |
| Narumi et al 27 | 75/M | NMOSD | NR | NR | NR | Spinal MRI: hyperintense lesions between C5-6 and Th12-L1 | Paraneoplastic autoantibodies: negative, AQP4 antibody: positive | WBC: 1195/µL, protein level: 380.9 mg/dL, glucose concentration: 40 mg/dL | NO |
| Horio et al 28 | 63/M | Trousseau syndrome | NR | NR | NR | Brain MRI: intratumor hemorrhage, small infarct near tumor, multiple cerebral infarcts | NR | NR | Brain hemorrhagic infarction |
| Tan et al 29 | 66/M | Cerebellar ataxia | NR | NR | NR | Brain CT: negative Brain MRI: small vessel disease |
Negative | Negative | NO |
Abbreviations: AChRAbs, anti-acetylcholine receptor antibodies; ALT, alanine aminotransferase; AQP4, aquaporin 4; AST, aspartate aminotransferase; CK, creatine kinase; CMAP, compound muscle action potential; CSF, cerebrospinal fluid; CT, computational tomography; EEG, electroencephalograph; EMG, electromyograph; GBS, Guillain-Barré syndrome; LDH, lactate dehydrogenase; MRI, magnetic resonance image; MUSK, muscle-specific tyrosine kinase; NCS, nerve conduction study; NMOSD, neuromyelitis optica spectrum disorder; NR, not reference; NSCLC, non-small cell lung cancer; PRES, posterior reversible encephalopathy syndrome; RNS, repetitive nerve stimulation; SFEMG, single-fiber electromyography; VGCC, voltage-gated calcium channel; WBC, white blood cell.