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Abstract

Objective: Deep neck space abscess (DNSA) is a serious infection associated with immune response. Magnesium has fundamental multifunctions in the body. Its insufficiency is involved in immüne weakness and susceptibility to infectious diseases. The present study addressed serum magnesium status in patients with DNSA. Herein, we hypothesized that patients with DNSA may have decreased serum magnesium concentration.

Materials and Methods: In the study, 23 patients with DNSA and 23 matched healthy individuals were included. The atomic absorption spectrometry was used to measure serum magnesium concentration. The groups were compared statistically for demographics and serum magnesium concentration.

Results: Patients with DNSA and healthy controls were statistically similar in age (p = .625), gender (p = 1.0), and smoking status (p = 1.0). However, patients with DNSA had significantly decreased serum magnesium concentration (µg/dL) than healthy controls [25.23 ± 4.98 (19.9-42.2) versus 31.98 ± 5.36 (26.8-40.8)], (p < .001).

Conclusion: This study demonstrated that decreased serum magnesium concentration is associated with DNSA. It is the first report on the research topic, and may inspire future studies.

Keywords

magnesium deep neck abscess immunodeficiency infection

Introduction

Deep neck space abscess (DNSA) is a severe infection that may cause life-threatening conditions.^1,2 The most common origin is odontogenic etiopathogenesis.³ Despite the general acceptance that DNSA originates from infection, the rate of positive bacterial culture is 30%–50%.² It has been reported that Streptococcus pyogenes and Staphylococcus aureus are predominant bacteria according to positive cultures.⁴ However, the bacterial positivity rate seems low therefore other factors, along with infections, may play a role in the pathogenesis of DNSA. The bacterial positivity rate seems low, and therefore it is thought that other factors, along with infections, may play a role in the pathogenesis of DNSA. In patients with DNSA, the most serious adverse consequences are respiratory and vascular complications, and sepsis.⁵ Due to its potentially severe consequences, the evaluation and treatment of DNSA should be started as quickly as possible.⁶ The combination of amoxicillin and clavulanate is the most commonly used antibiotherapy,^4,7 and the efforts to find more appropriate antibiotics continue.⁵

Magnesium is the second most abundant intracellular cation (K+ > Mg2+) and more than 99% of total body Mg2+ is stored intracellularly. This intracellular cation is necessary for various cellular functions such as energy production, oxidative phosphorylation and glycolysis, the synthesis of Deoxyribonucleic acid, Ribonucleic acid, and antioxidant glutathione. Magnesium also plays critical roles in the structural development of bone, maintenance of the electrical potential of nerve and heart tissues, and muscle contraction. Therefore, magnesium is needed for the maintenance of many fundamental biochemical reactions in the body.⁸

Magnesium deficiency may occur due to decreased intake and/or absorption, renal excretion and polypharmacotherapy interactions with age. Chronic magnesium deficiency can cause increased oxidative stress⁹ and low-degree inflammatory response.¹⁰ Thus, a susceptibility to infection and inflammation may occur, especially in the elderly. Magnesium can play a role in the immune response as a cofactor for immunoglobulin synthesis and other processes tightly associated with the function of T and B cells.¹¹ Magnesium is also required to biosynthesize, transport, and activate vitamin D, which is an important factor in the fight against infectious diseases.¹²

It is observed that the elderly are prone to both magnesium deficiency and DNSA.^1,5,6,9 In magnesium deficiency, it is possible that many of the protective biochemical reactions mentioned above slow down and the immune system weakens. This situation is likely to be associated with infection related diseases such as DNSA. Besides, chronic magnesium deficiency is associated with augmented baseline inflammatory reaction related to oxidative stress.^10,11 Considering the infection-predisposing^1,2,11 and inflammation-enhancing^9–11 effects of magnesium deficiency, as well as the infection origin and inflammatory nature of DNSA, it is reasonable and scientific to hypothesize that there may be an important relationship between magnesium deficiency and DNSA. Taking all together, the importance of magnesium for immune reactions and infectious diseases and the association of magnesium deficiency with various infections are worth considering.^9–13

However, to date, it has not been investigated whether magnesium deficiency is present in patients with DNSA. Therefore, the present study aimed to test the hypothesis that magnesium deficiency may be associated with DNSA, and to compare serum magnesium concentrations between patients with DNSA and healthy controls.

Materials and methods

This was a retrospective case-control study. Sample collection was conducted between January 2023 and December 2023. The local ethical approval was received retrospectively (date: January 12, 2024), no: 2024/01-16). This study was conducted following the ethical standards of the Declaration of Helsinki. A written informed consent was routinely obtained from all patients and healthy controls before any procedure was initiated.

In this study, 23 patients with DNSA and 23 matched healthy controls for age, gender, and smoking status were included. The frequency of affected deep neck spaces and the most frequently isolated bacteria in the patients with DNSA were recorded. Healthy controls were recruited from among the patients’ relatives or companions from the same geographical area. Healthy controls were also evaluated in terms of general symptoms and signs of infections or diseases such as pain, fever, sweating, high blood pressure, increased pulse as well as the blood cells including leukocytes, neutrophyles, lymphocytes, monocytes, and thrombocytes.

On the other hand, cases aged <18 and >65 years were excluded from this study. Also, pregnancy or lactation, fasting, mental illness or lack of cooperation, malignant diseases, immunodeficiency, penetrating neck injuries, gastrointestinal disabsorption, consuming immunosuppressive drugs or magnesium supplementation were exclusion reasons. In addition, normal individuals who had mentioned symptoms or signs suggestive of infection, inflammation, or diseases were excluded from the control group.

While samples were taken, participants were ensured to be in a resting and lying position after a 12-hour overnight fast and in the morning. Abscess drainage and multiple antibiotics were applied to all patients with DNSA.

Measurement of serum magnesium levels

The atomic absorption spectrometry (Thermo Scientific C103500100, Beijing, China) was used to determine serum magnesium concentrations. This is accepted as the reference method for the measurement of magnesium, since it provides the most accurate magnesium levels. However, it is not practical and has negative features such as expensiveness and technical difficulties.¹⁴ This method is based on the principle of absorbing electromagnetic rays of the element atoms gasified by increasing the temperature and calculating the absorbed beam according to the Lambert-Beer law.¹⁵ Accordingly, venous blood (4 mL) taken from participants was placed in a biochemistry tube. This blood sample was centrifuged at 3000 rpm for 10 minutes in a Nuve NF-800 brand centrifuge. Then, the serum was separated and kept at −20°C. On the day of processing, the stored samples were brought to room temperature (15 °C–18 °C) by carefully mixing and swirling. Then, 1 mL of serum and 1 mL of 20% TCA were taken into falcon tubes. These tubes were closed, vortexed, and kept in an oven at 90°C for 15 minutes. Then the samples were cooled and centrifuged. The obtained supernatant was taken into new tubes and analyzed.¹⁵

Statistical analyses

In the statistical analyses, the patient and control groups were compared in terms of clinical features including age, gender, smoking status, and laboratory features including magnesium levels, blood cells, and CRP levels. In addition, statistical correlations between magnesium and other laboratory parameters were analyzed.

The variables obtained from the groups were assessed and compared using statistical analyses performed with IBM SPSS version 20.0 (IBM Corp., Armonk, NY, USA). The Kolmogorov-Smirnov test was used to determine whether continuous variables had a normal distribution. Accordingly, CRP and monocyte scores in the DNSA group; and magnesium scores in the control group were found to be non-normally distributed. Parametric and non-parametric tests were applied for normally and non-normally distributed variables, respectively. The Mann-Whitney U test was used in the comparison of CRP, monocyte, and magnesium scores between the two groups. For the comparison of normally distributed continuous variables, the student t-test was used. The Fisher’s exact test was used to compare the categorical variables. In addition, the Pearson’s (for normal distributed variables) or the Spearman’s (for non-normal distributed variables) correlation tests were used in the statistical analyses of correlations between magnesium levels and other laboratory values. A p-value of <0.05 was considered statistically significant.

Results

The affected deep neck spaces were anterior triangle (n = 8), parapharyngeal (n = 4), retropharyngeal (n = 4), submandibular (n = 2), peritonsillar (n = 2), submental (n = 1), posterior triangle (n = 1), and parotid (n = 1) (Figure 1).

Figure 1.

Affected deep neck spaces. A: Anterior triangle (n = 8), B: Parapharyngeal (n = 4), C: Retropharyngeal (n = 4), D: Submandibular (n = 2), E: Peritonsillar (n = 2), F: Submental (n = 1), G: Posterior triangle (n = 1), and H: Parotid (n = 1).

The most commonly isolated bacteria were Staphylococcus aureus (21.74%) following by Streptococcus pyogenes (17.39%), and other rare bacterial agents (Table 1).

Table 1.

The bacteria isolated from DNSA.

Isolated bacteria	Patients n (%)
Staphylococcus aureus	5 (21.74)
Streptococcus pyogenes	4 (17.39)
Streptococcus constellatus	1 (4.35)
Staphylococcus hominis	1 (4.35)
Streptococcus viridans	1 (4.35)
Streptococcus oralis	1 (4.35)
Negative culture	10 (43.48)

Table 2 presents the comparison between the two groups regarding demographic features. The two groups had statistical similarity in terms of matched parameters including age (p = .625), gender (p = 1.0), and smoking status (p = 1.0). However, patients with DNSA had significantly elevated scores of leukocyte (p < .001), neutrophil (p < .001), monocyte (p < .012), and CRP (p < .001) compared to healthy controls (Table 1).

Table 2.

The characteristics of patients and healthy controls.

	Patients with deep neck abscess (n = 23)	Healthy controls (n = 23)	p
Age, years	34.82±11.43 (18-65)	33.04±13.07 (18-60)	0.625^a
Gender			1.0^b
Male	14 (61%)	14 (61%)
Female	9 (39%)	9 (39%)
Smoking status			1.0^b
Smoker	13 (57%)	13 (57%)
Non-smoker	10 (43%)	10 (43%)
Leukocyte, 10³/mL	12.83±4.22 (5.0-21.0)	6.60±1.59 (4.0-9.1)	<0.001^a
Neutrophil, 10³/mL	9.82±4.12 (2.75-19.0)	3.34±0.92 (1.30-4.87)	<0.001^a
Lymphocyte, 10³/mL	2.03±0.68 (1.0-2.80)	2.36±0.78 (1.16-3.75)	0.133^a
Monocyte, 10³/mL	0.89±0.38 (0.40-1.90)	0.65±0.41 (0.30-1.52)	0.012^c
Platelet, 10³/mL	294.6±72.1 (195-450)	258.9±58.5 (185-385)	0.072^a
CRP, mg/L	66.3±89.39 (3.2-297.0)	4.06±1.72 (1.0-7.26)	<0.001^c

^aThe student t-test.

^bThe Fisher’s exact test.

^cThe Mann-Whitney U test.

Figure 2 demonstrates the distribution of serum magnesium levels in the groups, and Figure 3 presents the comparison between the two groups in terms of serum levels of magnesium. Accordingly, serum magnesium concentrations showed a statistically significant difference between the two groups. More specifically, patients with DNSA had significantly decreased serum magnesium levels (µg/dL) compared to healthy controls [25.23 ± 4.98 (19.9–42.2) versus 31.98 ± 5.36 (26.8-40.8)], (p < .001).

Figure 2.

Distribution of serum magnesium levels in the groups.

Figure 3.

Serum magnesium levels (µg/dL) in the groups. Values were presented as mean ± SD (min.-max.).

Table 3 shows the statistical correlations of serum magnesium levels with other laboratory values. Accordingly, serum magnesium level was significantly and inversely correlated with CRP level in the DNSA group (r = −458, p = .028). However, there were no significant correlations between serum magnesium level and other laboratory values in healthy controls (p > .05, for all).

Table 3.

Correlations of magnesium with other laboratory values.

		Leukocyte	Neutrophil	Lymphocyte	Monocyte	Platelet	CRP
Patients with DNSA (n = 23)	r	−0.020	−0.042	0.204	−0.107	−0.206	−0.458
Patients with DNSA (n = 23)	p	0.928^a	0.847^a	0.351^a	0.627^a	0.346^a	0.028 ^b
Healthy controls (n = 23)	r	0.008	−0.241	0.278	0.090	−0.230	0.070
Healthy controls (n = 23)	p	0.970^b	0.268^b	0.199^b	0.682^b	0.290^b	0.750^b

^aThe Pearson’s correlation test.

^bThe Spearman’s correlation test.

Discussion

Herein, serum magnesium levels in patients with DNSA were addressed in a retrospective case-control study. As a result, patients with DNSA had lower serum magnesium concentrations than matched healthy controls. In addition, magnesium was significantly and inversely correlated with CRP in patients with DNSA. Therefore, from an etiopathogenetic perspective, decreased serum magnesium levels may be associated with DNSA. However, this was the first study to evaluate the research topic in the literature, and its results need to be confirmed.

Given the pivotal multifunctions of magnesium in the body,^8–13 it is possible that the insufficiency of magnesium can be involved in immune system weakness and susceptibility to infections. In light of this sensible and scientific hypothetical inference, the present study addressed serum magnesium status in patients with DNSA which represents a serious infection and is also related to immunodeficiency.^16,17 The results obtained in this study indicated that DNSA was associated with lower serum magnesium concentrations, manifesting in inverse correlation with CRP. Although no study to date has investigated the relationship between DNSA and magnesium, previous studies have displayed a significant inversely correlation of magnesium with CRP in various inflammatory disorders,^18–21 in consistent with our correlation findings in patients with DNSA. On the other hand, Coşkun Benlidayı et al²² have reported no significant correlation between serum magnesium level and CRP in patients with knee osteoarthritis. Similarly, we found no significant correlation between magnesium and CRP in healthy controls. These compatible findings suggest that magnesium and CRP are not correlated with each other in non-inflammatory conditions.

However, it is challenging to establish the causative factors of decreased serum magnesium levels in patients with DNSA that were detected in this study. Also, considering the case-control design of the study, it is not clear if this finding is a cause or consequence of DNSA. Therefore, several thoughts can be put forward regarding the emergence of this finding. For example, given various interactions between electrolytes,²³ reduced magnesium intake and other electrolytes due to appetite loss and pain or their increased use resulting from the disease may have caused decreased serum magnesium concentrations in patients with DNSA.

To date, serum magnesium concentrations in various disorders have been examined.²⁴ However, no studies have investigated the status of this fundamental element in patients with DNSA. Therefore, a detailed and in depth discussion section including comparative results from different studies could not be generated. Nevertheless, in parallel to our findings, Wang et al²⁵ have shown a strong association between magnesium deficiency and sepsis which is a similar condition to DNSA.

On the other hand, the limitations of this study should be considered. This was a planned retrospective case-control study limited to a certain period. Thus, the number of patients was 23 when the specified time expired. Thus, the study’s features including a small sample size, data from a single center, and a case-control design, are its main limitations. However, this is the first study on the relationship between DNSA and magnesium, and its limitations can be eliminated in further studies.

Conclusion

The results of this study showed that patients with DNSA have decreased serum magnesium levels. This finding suggests that magnesium insufficiency may be associated with DNSA etiopathogenesis. This was the first study on the research topic, and its results need to be confirmed. Also this study may inspire and guide the discovery of new motivations in future research.

Footnotes

Acknowledgments

The authors would like to extend their gratitude and acknowledgements to all patients and controls for their participation.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research,authorship,and/or publication of this article.

Funding

The author(s) received no financial support for the research,authorship,and/or publication of this article.

Ethical statement

ORCID iD

Canser Yilmaz Demir

Data availability statement

Data supporting the findings of this study are available. *

References

Treviño-Gonzalez

Maldonado-Chapa

González-Larios

, et al. Deep neck infections: demographic and clinical factors associated with poor outcomes. ORL J Otorhinolaryngol Relat Spec 2022; 84(2): 130–138.

Gao

Lin

Yue

, et al. Bacteriological analysis based on disease severity and clinical characteristics in patients with deep neck space abscess. BMC Infect Dis 2022; 22: 280.

Velhonoja

Lääveri

Soukka

, et al. Deep neck space infections: an upward trend and changing characteristics. Eur Arch Oto-Rhino-Laryngol 2020; 277(3): 863–872.

Beka

Lachanas

Doumas

, et al. Microorganisms involved in deep neck infection (DNIs) in Greece: detection, identification and susceptibility to antimicrobials. BMC Infect Dis 2019; 19(1): 850.

Sheikh

Heywood

, et al. The assessment and management of deep neck space infections in adults: a systematic review and qualitative evidence synthesis. Clin Otolaryngol 2023; 48(4): 540–562.

Loperfido

Stasolla

Giorgione

, et al. Management of deep neck space infections: a large tertiary center experience. Cureus 2023; 15(2): e34974.

Brito

Hazboun

Fernandes

, et al. Deep neck abscesses: study of 101 cases. Braz J Otorhinolaryngol 2017; 83: 341–348.

Fiorentini

Cappadone

Farruggia

, et al. Magnesium: biochemistry, nutrition, detection, and social impact of diseases linked to its deficiency. Nutrients 2021; 13(4): 1136.

Dominguez

Veronese

Guerrero-Romero

, et al. Magnesium in infectious diseases in older people. Nutrients 2021; 13(1): 180.

10.

Maier

Castiglioni

Locatelli

, et al. Magnesium and inflammation: advances and perspectives. Semin Cell Dev Biol 2021; 115: 37–44.

11.

Ashique

Kumar

Hussain

, et al. A narrative review on the role of magnesium in immune regulation, inflammation, infectious diseases, and cancer. J Health Popul Nutr 2023; 42(1): 74. doi: 10.1186/s41043-023-00423-0.

12.

Uwitonze

Razzaque

. Role of magnesium in vitamin D activation and function. J Am Osteopath Assoc 2018; 118(3): 181–189.

13.

Arancibia-Hernández

Hernández-Cruz

Pedraza-Chaverri

. Magnesium (Mg2+) deficiency, not well-recognized non-infectious pandemic: origin and consequence of chronic inflammatory and oxidative stress-associated diseases. Cell Physiol Biochem 2023; 57(S1): 1–23.

14.

Reddy

Soman

Yee

. Magnesium balance and measurement. Adv Chron Kidney Dis 2018; 25: 224–229.

15.

Olson

Hamlin

. A new method for serum iron and total iron-binding capacity by atomic absorption spectrophotometry. Clin Chem 1969; 15(6): 438–444.

16.

Srivanitchapoom

Sittitrai

Pattarasakulchai

, et al. Deep neck infection in Northern Thailand. Eur Arch Oto-Rhino-Laryngol 2012; 269(1): 241–246.

17.

Meher

Agarwal

Singh

. Tuberculous retropharyngeal abscess in an HIV patient. Hong Kong Med J 2006; 12(6): 483–485.

18.

Sadeghi

Khademi

Saneei

, et al. Dietary magnesium intake is inversely associated with ulcerative colitis: a case-control study. Crohns Colitis 360 2024; 6(1): otae009.

19.

Shahi

Aslani

Ataollahi

, et al. The role of magnesium in different inflammatory diseases. Inflammopharmacology 2019; 27(4): 649–661.

20.

Mazidi

Rezaie

Banach

. Effect of magnesium supplements on serum C-reactive protein: a systematic review and meta-analysis. Arch Med Sci 2018; 14(4): 707–716.

21.

Dong

Chen

Gutin

, et al. Magnesium intake, C-reactive protein, and muscle mass in adolescents. Nutrients 2022; 14(14): 2882.

22.

Coşkun

Bİ

Gökçen

Sarpel

. Serum magnesium level is not associated with inflammation in patients with knee osteoarthritis. Turk J Phys Med Rehabil 2017; 63(3): 249–252.

23.

Ab Rahim

Nordin

Wan

OWFA

, et al. The laboratory and clinical perspectives of magnesium imbalance. Cureus 2023; 15(12): e49835.

24.

Barbagallo

Veronese

Dominguez

. Magnesium in aging, health and diseases. Nutrients 2021; 13(2): 463.

25.

Wang

Zheng

, et al. Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis. Cell Death Differ 2020; 27(2): 466–481.