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Stress load and neurodegeneration after gastrostomy tube placement in amyotrophic lateral sclerosis patients

Abstract

Dysphagia and progressive swallowing problems due to motoneuron death is one of amyotrophic lateral sclerosis (ALS) symptoms. Malnutrition and body weight loss result in immunological disturbances, fatigability and increase risk of secondary complications in ALS patients, percutaneous endoscopic gastrostomy tube (PEG) placement representing a well-recognized method for malnutrition correction and potentially increasing life expectancy. However, despite nutritional correction, occasional rapid neurological deterioration may develop after PEG placement. We have hypothesized that this decline can be a result of exteroceptive stress during PEG placement and promote neurodegeneration in ALS patients. Intravenous sedation may decrease stress during invasive procedures and it is safe during PEG placement in ALS patients. The aim of the study was comparing different PEG placement protocols of anesthesia (local anesthesia or local anesthesia plus intravenous sedation) in ALS from perspectives of stress load and neurological deterioration profile. During 1.5 years 94 ALS patients were admitted; gastrostomy was performed in 79 patients. After screening according to inclusion and exclusion criteria, 30 patients were included in the prospective consecutive study. All patients were divided in two groups, with local anesthesia and with combination of local anesthesia and intravenous sedation. Routine biochemical indices, neurodegeneration and stress markers were measured. The age of ALS patients was 61 ± 10 years; 20 patients were included at stage 4A and 10 at stage 4B (King’s College staging). PEG was placed at average14 months after the diagnosis and 2.2 years after first symptoms. Mean ALS Functional Rating Scale-Revised was 27.8, mean forced vital capacity of lung 46.3% (19—91%). After one year of observation only 8 patients survived. Mean life duration after PEG was 5 months (5 days—20 months). Comparison of two PEG placement protocols did not reveal differences in survival time, stress load and inflammation level. Higher saliva cortisol levels, serum cortisol, glucose, C-reactive protein and interleukin-6 were detected after PEG placement, confirming considerable stress response. PEG is a stressful factor for ALS patients, PEG placement representing a natural model of exteroceptive stress. Stress response was detected as increased cortisol, C-reactive protein, interleukin-6, and glucose levels. Intravenous sedation did not increase the risk of PEG placement procedure, however, sedation protocol did not affect stress load.

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Availability of data and material

Due to the nature of this research, participants of this study did not agree for their data to be shared publicly, so supporting data is not available.

Code availability

Not applicable.

Abbreviations

ALS:

Amyotrophic lateral sclerosis;

ALSFRS-R:

ALS Functional Rating Scale-Revised;

BDNF:

Brain-derived neurotrophic factor;

BMI:

Body mass index;

CRP:

C-reactive protein;

ECAS:

Edinburgh Cognitive and Behavioral ALS Screen;

FVC:

Forced vital capacity;

Il-1β:

Interleukin-1β;

Il-6:

Interleukin-6;

PEG:

Percutaneous endoscopic gastrostomy tube;

pNfh:

Phosphorylated neurofilament heavy chains

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Funding

This study was performed with financial and organizational support by "Live Now" Charity Foundation for supporting people with ALS and other neuromuscular disorders (Moscow, Russia, https://alsfund.ru) and RFBR grant № 18–315-00228 mol_a.

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Affiliations

Authors

Contributions

Brylev L. – design and idea of the study, interpretation of data, manuscript preparation.

Fominykh V. – design the study, patient management, data analysis, interpretation of data, manuscript preparation and submission.

Chernenkaia V. – patients treatment and management, draft preparation, design of figures.

Chernenkiy I., Yakovlev A. – statistical support and analysis.

Gorbachev K., Ataulina A. Parshikov V., Demeshonok V. – patients management and technical works, biological fluids management and analysis.

Izvekov A., Monakhov M, Olenichev A, Orlov S, Turin I. – surgical procedures, PEG placement, data management.

Loginov M., Rautbart S. – anesthesiological management of patients, data management.

Baymukanov A. – analysis of cardiac function, design of cardiac evaluation.

Druzhkova T. – analysis of biomarkers, laboratory management.

Guekht A. – supervising, critical revising of intellectual content.

Gulyaeva N. – experimental design, supervising, critical revising of intellectual content.

Corresponding author

Correspondence to V. Fominykh.

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Conflicts of interest/Competing interests

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethics approval

This study was approved by the local Ethical Committee of Bujanov Moscow City Clinical Hospital. This study was performed in line with the principles of the Declaration of Helsinki.

Consent to participate, consent for publication

Informed consent was obtained from all individual participants included in the study.

All patients signed informed concern for data publication.

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Highlights

• PEG placement is a stress load for ALS patients

• Stress response can be detected by augmented cortisol, CRP and Il-6 levels

• After PEG placement, markers of stress response return to baseline

• Stress load does not depend on type of anesthesia

• Intravenous sedation does not increase the risk of PEG placement

• Normalization of total cholesterol after PEG confirms stabilization of nutritional status

Supplementary Information

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Brylev, L., Fominykh, V., Chernenkaia, V. et al. Stress load and neurodegeneration after gastrostomy tube placement in amyotrophic lateral sclerosis patients. Metab Brain Dis (2021). https://doi.org/10.1007/s11011-021-00837-x

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Keywords

  • ALS
  • Gastrostomy
  • Sedation
  • Neurodegeneration
  • Stress
  • Neuroinflammation