Table 1.
Case Reports and Management of Select Severe Neurologic irAEs
| Central Neurologic irAEs | ||||||
|---|---|---|---|---|---|---|
| Neurologic irAE | Grade | Checkpoint inhibitor | Approximate time to onset | Treatment of neurologic irAE | Outcome | Reference |
| Meningitis | ||||||
| Aseptic meningitis | 2 | Ipilimumab + nivolumab | 1‐2 wk | No treatment, ICI held then restarted | Complete resolution | Spain et al30 |
| Aseptic meningitis | 3 | Ipilimumab | 3‐5 wk | ICI stopped, no steroids due to spontaneous symptom improvement | Complete resolution | Spain et al30 |
| Aseptic meningitis | 3 | Ipilimumab | 3‐5 wk | Stop ICI, oral prednisolone | Complete resolution | Spain et al30 |
| Aseptic meningitis | N/A | Ipilimumab | 4 wk | Steroids administered | Resolved | Voskens et al31 |
| Aseptic meningitis | N/A | Ipilimumab (previous IL‐2) | 9‐11 wk | High‐dose dexamethasone | Compete resolution | Yang et al32 |
| Meningitis | N/A | Ipilimumab | 1‐3 wk | Dexamethasone 8 mg/day p.o. | Complete resolution | Bot et al24 |
| Meningitis | N/A | Atezolizumab | 1‐3 wk | No treatment; reinitiated w/o recurrence | Symptoms resolved | Genentech33 |
| Meningoencephalitis | ||||||
| Meningoencephalitis | N/A |
Ipilimumab + nivolumab |
19 wk |
ICI stopped; prednisone 100 mg/day tapered over 1 month | Full recovery | Fellner et al35 |
| Meningoencephalitis | N/A |
Ipilimumab + nivolumab |
12 wk |
ICI stopped then resumed 3 mo after symptom resolution; iv dexamethasone 10 mg twice daily for 8 d then tapered over 1 month | Full recovery | Fellner et al35 |
| Herpetic meningoencephalitis | N/A | Atezolizumab | 3 wk | No treatment | Patient died shortly thereafter from disease progression | Genentech33 |
| Encephalitis | ||||||
| Limbic encephalitis | N/A | Nivolumab | 5 d | iv dexamethasone 20 mg/day tapered over 12 d then oral prednisone 10 mg/day for 14 d followed by 5 mg/day | Full recovery | Fellner et al35 |
| Other | ||||||
| Cerebellar ataxia and dysarthria | N/A | Pembrolizumab | 29‐31 wk | ICI stopped; no treatment | Improved | Kao et al38 |
| Seizure | 2 |
Pembrolizumab (prior ipilimumab) |
7 wk | Levetiracetam 500 mg twice daily | Resolved; intracerebral bleeding 3 wk later | Zimmer et al39 |
| Seizure | 2 | Pembrolizumab | 20 wk | Lorazepam | Resolved | Zimmer et al39 |
| Recurring seizures; parkinsonoid/bradykinesia | 2 |
Pembrolizumab (prior ipilimumab) |
68 wk | ICI stopped; levetiracetam | Improved | Zimmer et al39 |
| Meningoradiculitis | 3 | Nivolumab | 9 wk | ICI stopped; dexamethasone 4 mg p.o. 4 times daily | Improved | Zimmer et al39 |
| Cranial polyneuropathy | N/A |
Ipilimumab + nivolumab |
8 wk | ICI stopped; prednisone 60 mg/day then tapered over 3 mo | Full recovery | Fellner et al35 |
| Phrenic nerve palsy with bulbar palsy | 4 | Nivolumab | 7 wk | ICI stopped; methylprednisolone 1 mg/kg; IVIG; pyridostigmine | Complete resolution | Spain et al30 |
| Peripheral Neurologic irAEs | ||||||
|---|---|---|---|---|---|---|
| Neurologic irAE | Grade | Checkpoint inhibitor | Approximate time to onset | Treatment of neurologic irAE | Outcome | Reference |
| Neuromuscular Junction Disorders | ||||||
| Myasthenia gravis/ paralysis (eyelids/hands) | 4 | Pembrolizumab (prior ipilimumab) | 10 wk | Methylprednisolone 1 gram iv for 3 d; pyridostigmine 30 mg p.o. for 3 d, plasmapheresis | Not resolved; death | Zimmer et al39 |
| Myasthenic crisis and polymyositis | N/A | Nivolumab | 2 wk | Steroids administered; immune absorption therapy; plasma exchange therapy; IVIG | N/A | Kimura et al40 |
| Demyelinating Disorders | ||||||
| Polyradiculitis | N/A |
Ipilimumab + nivolumab |
8 wk | ICI stopped; prednisone 80 mg/day tapered over 2 mo | Full recovery | Fellner et al35 |
| Polyradiculitis | N/A | Pembrolizumab | 18 wk | ICI stopped; iv methylprednisolone 1 gram/day tapered over 10 d then prednisone 80 mg/day tapered over 2 mo | Partial recovery | Fellner et al35 |
| Polyradiculitis | 3 | Pembrolizumab (prior ipilimumab) | 35 wk | ICI paused; prednisolone 1 gram iv then p.o. tapering | Improved | Zimmer et al39 |
| Polyneuropathy | 2 | Pembrolizumab | 4 wk | Pregabalin 75 mg p.o. twice daily | Not resolved | Zimmer et al39 |
| Polyneuropathy, worsening | 2 | Pembrolizumab (prior ipilimumab) | 6 wk | Magnesium | Not resolved | Zimmer et al39 |
| Sensorimotor neuropathy with bulbar palsy (Guillain‐Barré‐like syndrome) | 4 | Ipilimumab | 10 wk | ICI stopped; methylprednisolone 2 mg/kg; plasmapheresis | Partial improvement | Spain et al30 |
| Axonal Guillain‐Barré syndrome | 5 | Ipilimumab | 12 wk | IVIG 0.4 gram/kg for 5 d | Death secondary to respiratory failure 3 d after starting IVIG | Bot et al24 |
| Other | ||||||
| Tolosa‐Hunt syndrome | N/A | Ipilimumab | 18 wk | Methylprednisolone iv followed by dexamethasone p.o., local radiotherapy | Ongoing | Voskens et al31 |
| Paresis, neuritis (oculomotor nerve) | 2 | Pembrolizumab (prior ipilimumab) | 13 wk | ICI paused; prednisolone 100 mg/day | Resolved | Zimmer et al39 |
| Paresis (abducens nerve, facial nerve) | 3 | Nivolumab (prior ipilimumab) | 6 wk | ICI paused; methylprednisolone 1 mg/kg/day; IVIG | Resolved | Zimmer et al39 |
| Severe necrotizing myopathy | N/A | Pembrolizumab | 3‐5 wk | ICI stopped; prednisone 80 mg/day for 12 d; plasmapheresis | Death | Kao et al38 |
| Facial nerve paralysis | N/A | Ipilimumab | 7 wk | Steroids administered | Resolved | Voskens et al31 |