CNS and PNS manifestation in immune checkpoint inhibitors: A systematic review

Khan, Erum; Shrestha, Ashish K.; Elkhooly, Mahmoud; Wilson, Hannah; Ebbert, Michael; Srivastava, Samiksha; Wen, Sijin; Rollins, Steven; Sriwastava, Shitiz

doi:10.1016/j.jns.2021.120089

Cited by 15 publications

(22 citation statements)

References 56 publications

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“…Notably, patients who used nervous system drugs had a significantly higher risk of fatal outcomes in the analysis ( Table 2 ). Furthermore, ICI-related urine incontinence always occurs concomitantly with neuromuscular irAEs or neuromuscular–cardiovascular overlapping syndrome, both of which have high risks of mortality and are difficult to manage ( 13 , 39 , 40 ). Therefore, further investigation into the prognosis and mortality of ICI-related urine incontinence is needed.…”

Section: Discussionmentioning

confidence: 99%

Urinary incontinence as a possible signal of neuromuscular toxicity during immune checkpoint inhibitor treatment: Case report and retrospective pharmacovigilance study

Lu²,

Tang³

et al. 2022

Front. Oncol.

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BackgroundImmune checkpoint inhibitors (ICIs) are associated with different immune-related adverse events (irAEs), but there is limited evidence regarding the association between urinary incontinence and ICIs.MethodsWe described the case of a patient experiencing urinary incontinence who later experienced a series of irAEs such as myocarditis, myositis, and neurologic diseases while on ICI treatment in our hospital. In addition, we queried the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from the third quarter of 2010 to the third quarter of 2020 to perform a retrospective study to characterize the clinical features of urinary incontinence associated with ICIs.ResultIn the FAERS study, 59 cases of ICI-related urinary incontinence were retrieved, and approximately 32.2% of the cases were fatal. Combination therapy with nervous system drugs and age >80 years old were the significant risk factors for fatal outcomes. Among these cases of ICI-related urinary incontinence, 40.7% (n = 24) occurred concomitantly with other adverse events, especially, neurological (fifteen cases), cardiovascular (seven cases), musculoskeletal (six cases), and urological disorders (five cases). Five cases had an overlapping syndrome similar to our case report, including one case of myasthenia gravis with myocarditis and another of myasthenic syndrome with polymyositis.ConclusionICI-related urinary incontinence might be a signal of fatal neuromuscular irAEs, especially when it occurs concomitantly with ICI-associated neuromuscular–cardiovascular syndrome. Clinicians should be aware of the occurrence of urinary incontinence to identify potentially lethal irAEs in the early phase.

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Section: Discussionmentioning

confidence: 99%

Urinary incontinence as a possible signal of neuromuscular toxicity during immune checkpoint inhibitor treatment: Case report and retrospective pharmacovigilance study

Lu²,

Tang³

et al. 2022

Front. Oncol.

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“…Cuzzubbo et al [ 42 ] found a 5% incidence in 2017, while a 2022 meta-analysis (including newer PD-L1 inhibitors) showed a 15% incidence (70% from anti-PD-1/PD-L1) [ 43 ]. Peripheral nervous system (PNS) irAEs are 2–5 times more common than central nervous system (CNS) toxicity [ [44] , [45] , [46] ]. In the largest systematic review of NirAE cases to date, 85% were above age >50 years, and men made up 2/3 [ 46 ].…”

Section: Neurological Immune-related Adverse Eventsmentioning

confidence: 99%

“…Peripheral nervous system (PNS) irAEs are 2–5 times more common than central nervous system (CNS) toxicity [ [44] , [45] , [46] ]. In the largest systematic review of NirAE cases to date, 85% were above age >50 years, and men made up 2/3 [ 46 ]. CNS/PNS overlap syndromes occur at a rate of 18% [ 47 ].…”

Section: Neurological Immune-related Adverse Eventsmentioning

confidence: 99%

“…The mortality rate of NirAEs varies from 8.4% (mostly from MG and myositis) [ 41 ] to 11% (seen in multi-national pharmacovigilance data) [ 50 ]. This makes it imperative that they be promptly recognized and treated [ 46 , 51 ]. Another study found MG (28%), encephalitis (21%), and GBS (11%) had the highest mortality rates while meningitis, myelitis, and cranial neuropathy had none [ 45 ].…”

Section: Neurological Immune-related Adverse Eventsmentioning

confidence: 99%

“…Corticosteroids were used in only 2 cases [ 104 , 107 ]. Reversible posterior leukoencephalopathy syndrome is not clearly an irAE and is not included in any of the guidelines; however, some authors classify it as such [ 46 , 56 ].…”

Section: Central Nervous System Neurological Immune Related Adverse E...mentioning

confidence: 99%

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CNS and PNS manifestation in immune checkpoint inhibitors: A systematic review

Cited by 15 publications

References 56 publications

Urinary incontinence as a possible signal of neuromuscular toxicity during immune checkpoint inhibitor treatment: Case report and retrospective pharmacovigilance study

Urinary incontinence as a possible signal of neuromuscular toxicity during immune checkpoint inhibitor treatment: Case report and retrospective pharmacovigilance study

Evaluation and management of acute high-grade immunotherapy-related neurotoxicity

Immune Checkpoint Inhibitors in Patients with Pre-existing Neurologic Autoimmune Disorders

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