scholarly journals Immune-Related Neurological Toxicities of PD-1/PD-L1 Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Yuan Tian ◽  
Aiqin Gao ◽  
Qing Wen ◽  
Shuyun Wang ◽  
Shuisheng Zhang ◽  
...  

BackgroundSystematic assessment of PD-1/PD-L1 inhibitor-related neurological toxicities is important for guiding anti-PD-1 and anti-PD-L1 immunotherapy. Therefore, we conducted this meta-analysis to reveal the relationship between PD-1/PD-L1 inhibitors and neurological toxicities among cancer patients.MethodsClinical trials investigating PD-1/PD-L1 inhibitors in cancer patients were identified by a systematic search of PubMed. The random-effect model was used to synthesize individual studies. Neurological toxicities, including all-grades and grades 3–5, were taken into account for the final comprehensive meta-analysis. The Newcastle Ottawa Scale (NOS) was used to assess the quality of included trials.ResultsThirty-one clinical trials containing data of neurological toxicities were included. Compared with chemotherapy, the risk of all-grade neurological toxicities caused by PD-1/PD-L1 inhibitors was much lower in terms of peripheral neuropathy [OR = 0.07, 95%CI:(0.04, 0.13)], peripheral sensory neuropathy [OR = 0.07, 95%CI(0.04, 0.12)], dysgeusia [OR = 0.26, 95%CI:(0.19, 0.35)], paraesthesia [OR = 0.23, 95%CI:(0.14, 0.36)], and polyneuropathy [OR = 0.12, 95%CI:(0.01, 0.94)]. However, for grades 3–5, the statistically significant results were only seen in peripheral neuropathy [OR = 0.15, 95%CI:(0.07, 0.34)] and peripheral sensory neuropathy [OR = 0.13, 95%CI:(0.04, 0.40)]. No statistically significant difference regarding the risk of headache, dizziness, and Guillain–Barré syndrome was found between PD-1/PD-L1 inhibitors and chemotherapy. For PD-1/PD-L1 inhibitors plus chemotherapy, the risk trends of the above-mentioned neurological toxicities, especially grades 3–5 peripheral neuropathy [OR = 1.76, 95%CI:(1.10, 2.82)] was increased compared to chemotherapy alone.ConclusionOur comprehensive analysis showed that PD-1/PD-L1 inhibitors alone exhibited lower neurological toxicities than chemotherapy. However, the risk of headache, dizziness, and Guillain–Barré syndrome was similar between PD-1/PD-L1 and chemotherapy. For PD-1/PD-L1 inhibitors plus chemotherapy, the incidence trend of neurological toxicities would be increased, especially for peripheral neuropathy of grades 3–5.

2020 ◽  
Author(s):  
Jingfeng Lin ◽  
Qiang Gao ◽  
Kang Xiao ◽  
Danfeng Tian ◽  
Wenyue Hu ◽  
...  

Abstract Background Guillain-Barre syndrome (GBS) is an acute, paralyzing, inflammatory peripheral nerve disease. For treatments of the Guillain-Barre Syndrome, there are many kinds of therapies for this diseases. For comparing all of the therapies, such as immunoglobulin, plasma exchanging, etc. in the treatment of Guillain-Barre Syndrome(GBS) to better inform clinical practice, we use Network meta analysis to get the outcome of the Guillain-Barre Syndrome. The protocol has been submitted to PROSPERO:CRD: 42019119178. Methods Web of Science, PubMed, Embase, and the Cochrane library were searched for related articles. We identified citations of these and included 26 trials comprising 2434 patients and control group human beings. Network meta-analysis (NMA) was performed with two kinds of outcomes. We carried on R software with gemtc package and JAGS software to calculate results for different therapies. The consistency of direct and indirect evidence was also assessed by R software. Results Concerning for two outcomes, there were no improvement observed in MTP and Pred compared with placebo. PE and IVIg were illustrated to be effective over Placebo. There was no significant difference between different doses and times of PE and IVIg. On consistency examination between direct and indirect evidences, there were no obvious heterogeneity between all of therapies. Funnel plots indicates the possibility of publication bias in this study are small. Conclusion PE or IVIg had a significant efficency for GBS patients. The effects of some combination treatments should be further explored. Corticosteroids had no significant effects on GBS.


2021 ◽  
Author(s):  
Yasmim Nadime José Frigo ◽  
Hendrick Henrique Fernandes Gramasco ◽  
Ana Flavia Andrade ◽  
Guilherme Drumond Jardini Anastácio ◽  
Stella de Angelis Trivellato ◽  
...  

Introduction: Guillain-Barré syndrome is an acute / subacute inflammatory polyradiculoneuropathy that classically results in flaccid areflex palsy. However, there are other possibilities of clinical presentation that must be remembered so that an adequate diagnosis and treatment is carried out. Case report: Female patient, 23 years old, without comorbidities, with complaint of paresthesia in extremities and right peripheral facial paralysis, having diagnosis until then of Bell’s Palsy. She denied previous or current infectious complaints. The neurological examination revealed facial diparesis, proximal weakness of the lower limbs that made walking difficult, tactile and painful hypoesthesia in the feet, with reflexes 1+/4+ in the lower limbs and 3+/4+ in the upper limbs. An investigation was started with CSF collection that showed albuminocytological dissociation (proteins 440 mg/dl and leukocytes 01 mm3). Neuroimaging exams showed contrast impregnation in facial and trigeminal nerves. A diagnosis of acute inflammatory polyradiculoneuropathy was made and treatment with human immunoglobulin was initiated for 5 days. Electroneuromyography showed peripheral, sensory-motor polyradiculoneuropathy and questioned the physiopathological possibility of juxtaparanodopathy. The patient presented a significant and early improvement after treatment. Conclusions: It is essential to consider that Guillain-Barré syndrome has symptom variability, especially according to its pathophysiology and clinical and electrophysiological variant, thus avoiding that conditions such as this one are underdiagnosed.


2020 ◽  
Vol 14 (4) ◽  
pp. e0008264 ◽  
Author(s):  
Sonja E. Leonhard ◽  
Cristiane C. Bresani-Salvi ◽  
Joanna D. Lyra Batista ◽  
Sergio Cunha ◽  
Bart C. Jacobs ◽  
...  

2021 ◽  
Vol 39 (4) ◽  
pp. 347-350
Author(s):  
Ga Yeon Kim ◽  
Bo Ra Kim ◽  
Jong Kuk Kim ◽  
Byeol-A Yoon

Acute autonomic and sensory neuropathy (AASN) is very rare immune mediated neuropathy characterized by prominent dysautonomia and sensory involvement without motor weakness. Most of AASN patients have a rapid onset reaching its worst within four weeks like Guillain-Barré syndrome. The treatment response is variable. Recently, we experienced a patient diagnosed as AASN with progressive autonomic and sensory symptoms more than 1 year, and showed good response in immunotherapy.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
John D. Morrey ◽  
Alexandre L. R. Oliveira ◽  
Hong Wang ◽  
Katherine Zukor ◽  
Mateus Vidigal de Castro ◽  
...  

AbstractClinical evidence is mounting that Zika virus can contribute to Guillain-Barré syndrome which causes temporary paralysis, yet the mechanism is unknown. We investigated the mechanism of temporary acute flaccid paralysis caused by Zika virus infection in aged interferon αβ-receptor knockout mice used for their susceptibility to infection. Twenty-five to thirty-five percent of mice infected subcutaneously with Zika virus developed motor deficits including acute flaccid paralysis that peaked 8-10 days after viral challenge. These mice recovered within a week. Despite Zika virus infection in the spinal cord, motor neurons were not destroyed. We examined ultrastructures of motor neurons and synapses by transmission electron microscopy. The percent coverage of motor neurons by boutons was reduced by 20%; more specifically, flattened-vesicle boutons were reduced by 46%, and were normalized in recovering mice. Using electromyographic procedures employed in people to help diagnose Guillain-Barré syndrome, we determined that nerve conduction velocities between the sciatic notch and the gastrocnemius muscle were unchanged in paralyzed mice. However, F-wave latencies were increased in paralyzed mice, which suggests that neuropathy may exist between the sciatic notch to the nerve rootlets. Reversible synaptic retraction may be a previously unrecognized cofactor along with peripheral neuropathy for the development of Guillain-Barré syndrome during Zika virus outbreaks.


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