Syphilis is a chronic sexually transmitted disease caused by an infection with Treponema pallidum. Neurosyphilis is an irreversible disease caused by the invasion of Treponema pallidum into the central nervous system, leading to brain parenchyma destruction and central nervous system impairment [1, 2]. Lumbar puncture (LP) remains the gold-standard diagnostic procedure for neurosyphilis. However, post-LP adverse reactions, particularly post-dural puncture headache (PDPH), remain a significant clinical challenge across various populations, with reported incidence rates ranging from 10% to 40% [3, 4].

At present, the risk factors for post-LP adverse reactions remain undetermined in existing literature. Among the key determinants for the post-LP adverse reactions that have been investigated are needle size [5, 6], patient positioning [7, 8], body mass index (BMI) [5, 9, 10], and fluid replacement volume [11]. Notably, there is limited data specifically addressing syphilis patients, who may present unique characteristics due to potential central nervous system involvement. Given this knowledge gap, the current study aims to systematically evaluate the incidence, clinical manifestations, and risk factors of post-LP adverse reactions in syphilis patients.

LP is an essential diagnostic tool for neurological diseases, with primary diagnostic indications including infectious diseases, inflammation, and related conditions affecting the central nervous system [13, 14]. In our department, syphilis patients constitute 95% of the inpatients, and thus, LP stands as an essential approach to distinguishing patients with syphilis from those with neurosyphilis. PDPH is a widely recognised common complication after LP, with symptoms including neck stiffness, lower back soreness, nausea, vomiting, as well as ear and eye symptoms [15]. PDPH is a typical positional headache that worsens when the patient is upright and improves or resolves when lying flat, typically lasting for several days with severity ranging from mild to debilitating; in severe cases, medical intervention may be required [16, 17, 18]. Post-procedural lower back soreness and pain refer to pain around the puncture site in the spine [19]. According to several studies, the occurrence rates of PDPH range from 3% to 30% [11, 20]. Meanwhile, our research findings indicate that 24.8% of syphilis patients experienced adverse reactions following an LP, with headache/dizziness being the most common adverse reaction, occurring in 59.2% of cases, followed by back pain noted in 47.9% of the cases.

Our research results indicated that the thickness of the puncture needle influences the occurrence of post-LP adverse reactions. Specifically, the use of an 18G puncture needle (1.2 mm) relative to a 20G needle (0.9 mm) increased the risk of post-procedural adverse reactions, consistent with the findings of Azzi et al. [3] and Destrebecq et al. [21], who recommended that smaller needles could significantly reduce the incidence of PDPH. This may be attributed to reduced dural trauma associated with a smaller skin puncture created by a finer needle [22, 23, 24], which can result in slower cerebrospinal fluid outflow during the procedure and a lower risk of post-procedural leakage at the puncture site. Therefore, smaller-gauge needles are recommended for use during the LP procedures in order to reduce the occurrence of adverse reactions in patients.

This study demonstrated that the likelihood of adverse reactions following LP decreased with advancing age. This finding contrasts with several previous reports indicating a lower rate of PDPH in patients with cognitive impairment and a higher incidence of post-procedural adverse reactions in younger populations—patterns that align with the observed rarity of such reactions in both infants and the elderly [25, 26, 27]. This trend may be attributed to the decline in cognitive impairment or the gradual onset of brain atrophy with advancing age. Additionally, it has been reported that older age acts as a protective factor against post-LP headaches [11, 28, 29].

Patients with paralytic dementia exhibit abnormal mental and behavioural symptoms, such as lack of concentration, forgetfulness, reduced judgment and memory, cognitive impairment, dementia, mood swings, depression, personality changes, delusions, mania, or psychosis [2, 30]. The results of this study indicate that symptoms of paralytic dementia act as a protective factor against adverse reactions after LP. El-Mallakh et al. [31] reported that post-LP headaches are less frequent and severe in patients with schizophrenia compared to normal individuals, due to the reduced pain perception in mentally ill patients (i.e., higher pain threshold) [32] and decreased ability to verbally express pain (i.e., reduced tendency to complain) [33]. This aligns with our research findings, although the exact mechanisms remain unclear.

In the current clinical practice, patients are typically advised to lie flat without a pillow for 4–6 hours after LP for the reason of reducing the risk of adverse reactions. However, our study found that bed rest exceeding 6 hours was associated with an increased incidence of postoperative adverse reactions.

The adverse reaction may arise from prolonged immobilisation, coupled with anxiety toward postoperative complications, which eventually causes sleep disruptions. Extended bed rest can also lead to muscle tension, hindering relaxation and resulting in lower back pain and soreness. Furthermore, patients who remain supine without pillows for more than 6 hours typically exhibit decreased water intake compared to their more active counterparts, and the production rate of cerebrospinal fluid is also diminished. In contrast to other studies, our findings suggest that post-LP bed rest, regardless of the duration, does not contribute to lowered incidence of PDPH [34, 35]. Specifically, our results contradict the findings of Zhang [36], which indicate that haematology patients who took rest for $\le$2 hours after LP are more likely to experience post-procedural headaches, which can be caused by the higher volume of cerebrospinal fluid collected during diagnostic LP in syphilis patients.

There are several limitations in this study. Firstly, this was a single-center study with a small sample size; therefore, additional multi-center studies with larger cohorts are needed in the future. In addition, several critical variables, such as syphilis stage, patient complications, disease course, and type of treatment, were not considered in our analysis, and it is currently unknown if the collection speed of cerebrospinal fluid during LP would affect the incidence of postoperative complications. Therefore, an in-depth study of the above-mentioned factors is warranted in the future.

Our study provides several novel insights into post-LP adverse reactions, which impact approximately one-quarter (24.8%) of syphilis patients. These reactions primarily manifest as headache/dizziness (59.2%) or back pain (47.9%), possibly indicating unique pathophysiological changes in the meninges of syphilis patients. The use of small-gauge needles (20G), age $>$30 years, paralytic dementia, and a bed rest period 6 hours are protective factors in the context of adverse reactions affecting syphilis patients after receiving LP. These findings highlight the need for personalised post-LP management in specific patient populations. Healthcare providers should apply evidence-based practices while remaining vigilant for individual patient variations.

$\bullet$ The incidence of adverse reactions after lumbar puncture in patients with syphilis was as high as 24.8%, with headache/dizziness (59.2%) and back pain (47.9%) being the most common adverse reactions.

$\bullet$ Key factors that contribute to reduced incidence of these adverse reactions include the use of small-gauge needles (20G), age $>$30 years, paralytic dementia, and a bed rest period 6 hours.

$\bullet$ The risk factors identified in this study form the clinical basis for assessing patients who may be susceptible to adverse reactions and implementing measures to minimise their occurrence, thereby enhancing clinical practice.

The datasets generated during and/or analysed during the current study are available from the corresponding authors upon reasonable request.

Conceptualization: JY, LZ, YW, FL; Methodology: LZ, FL; Formal analysis and investigation: JY, YW, XX; Writing—original draft preparation: JY, LZ, YW, FL; Writing—review and editing: LZ. All authors contributed to the important editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study adhered to the Declaration of Helsinki and received approval from the Ethics Committee of Shanghai Skin Disease Hospital (approval number: 2024-37). Written informed consent was obtained from all participants, and all data used for research analyses were anonymised.

Not applicable.

This research received no external funding.

The authors declare no conflict of interest.