Article Text

Original research
Multidisciplinary re-evaluation of neuropsychiatric events to confirm the neuropsychiatric lupus diagnosis at an Indonesian tertiary hospital
  1. Riwanti Estiasari1,2,
  2. Syairah Banu1,2,
  3. Alvina Widhani2,3,
  4. Fitri Octaviana1,2,
  5. Kartika Maharani1,2,
  6. Tiara Aninditha1,2,
  7. Muthia Huda Islami1,
  8. Darma Imran1,2 and
  9. Diatri Nari Lastri1,2
  1. 1Faculty of Medicine, Department of Neurology, Universitas Indonesia, Jakarta, Indonesia
  2. 2Rumah Sakit Umum Pusat Nasional Dr Cipto Mangunkusumo, Central Jakarta, Indonesia
  3. 3Faculty of Medicine, Department of Internal Medicine, Universitas Indonesia, Jakarta, Indonesia
  1. Correspondence to Dr Riwanti Estiasari; riwanti.estiasari04{at}ui.ac.id

Abstract

Objective Neuropsychiatric SLE (NPSLE) has a broad spectrum and to date, there is no gold-standard biomarker. The diagnosis relies on clinical assessment, supporting examinations and exclusion of other possible aetiologies. One method that can be used to establish NPSLE is to conduct a re-evaluation by involving several fields of medical science. This study aims to reassess SLE cases with neuropsychiatric (NP) manifestations through multidisciplinary re-evaluation and determine the final diagnosis of NPSLE or non-NPSLE.

Methods This retrospective cross-sectional study used medical record data from patients with SLE with NP manifestations. Inclusion criteria included patients diagnosed with SLE, who had clinical manifestations of NP and were >18 years old. Multidisciplinary re-evaluation was conducted and agreed upon the diagnosis of NPSLE or non-NPSLE.

Results We included 94 subjects with a total of 132 NP events consisting of 69 NPSLE and 63 non-NPSLE. After re-evaluating NPSLE events, 33.3% were still concluded to be NPSLE. Meanwhile, from the non-NPSLE group, 22.2% were then declared as NPSLE. There were no significant differences in demographic characteristics between the NPSLE and non-NPSLE groups. The proportion of NP events in both groups was almost the same except for cerebrovascular disease manifestations which were more common in the NPSLE group. Higher Mexican SLE Disease Activity Index scores with (p<0.001) or without NP (p=0.02) were observed in the NPSLE group compared with the non-NPSLE group, as well as higher proportion of active disease (p=0.03), higher anti-double-stranded DNA titres (p<0.001) and lower values of C3 (p=0.018) and C4 (p=0.001).

Conclusions Multidisciplinary re-evaluation can be used as a method to confirm the diagnosis of NPSLE. There is a tendency for overdiagnosis of NPSLE when clinicians are faced with NP events in patients with SLE. Complete clinical and supporting data are needed to determine the final diagnosis of NPSLE.

  • Lupus Erythematosus, Systemic
  • Autoimmune Diseases
  • Inflammation

Data availability statement

Data are available upon reasonable request.

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WHAT IS ALREADY KNOWN ON THIS TOPIC

  • The symptoms of neuropsychiatric SLE (NPSLE) are highly variable. There is no satisfactory biomarker to diagnose NPSLE.

WHAT THIS STUDY ADDS

  • This study found a trend towards overdiagnosis of NPSLE. Of the 69 events that were initially classified as NPSLE, only 23 (33.3%) were diagnosed as NPSLE after re-evaluation.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • Our study highlights the role of multidisciplinary evaluation in establishing the diagnosis of NPSLE.

Introduction

Neuropsychiatric SLE (NPSLE) is defined as a syndrome that includes central nervous system manifestation as well as peripheral nervous system and/or psychiatric manifestation that ranges from mild to severe abnormality spectrum in patients with SLE after other aetiologies are excluded.1 Its pathogenesis mechanism is related to SLE progression. The American College of Rheumatology (ACR) described and classified NPSLE criteria spectrum into 19 syndromes of central nervous system and peripheral nervous system.2 3 Therefore, not all neuropsychiatric (NP) manifestations in SLE can be concluded as NPSLE.

The prevalence of NPSLE was reported variably across the world, ranging from 14% to 95%.3 The national data in Indonesia regarding its prevalence are still limited as it has been reported more often as case reports or small studies in short duration. A study conducted at Dr Cipto Mangunkusumo Hospital in 2011 found 63.8% of patients with SLE had cognitive impairment with executive and visuospatial function as the most frequently impaired functions.4 However, this study did not evaluate other possible causes of the cognitive impairment found, so it cannot be concluded that all cognitive disorders were attributable to SLE.

Diagnosing NPSLE remains an arduous challenge due to its widely variant and non-specific manifestation, thus creating a hindrance to differentiate the NP manifestation caused by other aetiologies. Furthermore, up to this point, the gold standard or the definite in vivo biomarker of NPSLE has not been discovered. Another difficulty in diagnosing NPSLE is that attribution process of NP manifestation in SLE is complex and time-consuming.5

Currently, the multidisciplinary consensus remains the reference standard of NPSLE diagnosis even though this approach has some disadvantages such as the high variability in diagnosis between healthcare centres, and the low accuracy of diagnostic criteria due to its inability to precisely portray NPSLE.6 Diagnostic criteria that are commonly used are the 1999 ACR criteria, although a validation study by Ainiala et al found that the specificity of the criteria was low.7 Diagnostic criteria have also been formulated by the Italian Society of Rheumatology (ISR).8 However, the criteria are also considered to be inaccurate.7 A study by Magro-Checa et al emphasised the importance of multidisciplinary re-evaluation regarding NP manifestation in SLE to minimise the potential of misclassification and to improve diagnosis accuracy.6

Thus far, not all of SLE cases with NP manifestation at Dr Cipto Mangunkusumo Hospital, Jakarta, Indonesia have been multidisciplinary re-evaluated to confirm the NPSLE diagnosis. Therefore, this study was conducted to highlight the pivotal role of multidisciplinary re-evaluation of NP manifestation in SLE and to compare the clinical and diagnostic test characteristics between the group of NPSLE and NP manifestations caused by other aetiologies (non-NPSLE).

Methods

This cross-sectional study was conducted using secondary data collected from medical records in Dr Cipto Mangunkusumo Central Hospital, Jakarta, which were recorded from January 2022 until December 2022. Patients who meet inclusion criteria—patients with SLE,1 more than 18 years old and presented with NP manifestation—were recruited using consecutive sampling.

Organ involvement was defined according to a recommendation by the Indonesian Rheumatological Association regarding SLE diagnosis and treatment in 2019.1 The clinical syndrome of NPSLE was classified based on ACR criteria in 1999.2 The SLE disease activity was assessed using the Mexican SLE Disease Activity Index (MEX-SLEDAI).9 A multidisciplinary re-evaluation of NP manifestation in patients with SLE was done by a team that included neurologists subspecialised in neuroimmunology and neurophysiology and internists subspecialised in allergy and clinical immunology. During re-evaluation, analyses of the aetiologies of NP manifestations in SLE were thoroughly discussed. NPSLE was defined as the case in which NP manifestation was associated with SLE, whereas non-NPSLE was defined as the case in which NP manifestation was caused whether by other aetiologies or unknown aetiologies.

Statistical analysis was done using IBM SPSS V.22 for Windows. The categorical data were presented as frequency and percentage, and bivariate analysis was done using Χ2 or Fisher’s exact test. When not normally distributed, numerical data were presented as median value and then analysed with Mann-Whitney test. The association between variables would be considered significant if p<0.05. Multivariate analysis was performed using logistic regression.

Results

There were 94 patients with SLE with NP syndromes included in this study. About 64 of them (68.1%) had a single NP manifestation and 30 of them (31.9%) displayed multiple manifestations. Among 30 subjects with multiple manifestations, 23 of them (76.7%) presented with two NP manifestations, whereas 6 of them (20%) presented three and only 1 of them (3.3%) exhibited four NP manifestations.

Initially, there were 133 NP events from 94 patients with SLE with 69 NP events suspected as NPSLE and 64 NP events as non-NPSLE. One case was not analysed because it was determined as a case of SLE with musculoskeletal manifestation during re-evaluation; consequently, there were 132 events in total (69 NPSLE events and 63 non-NPSLE events). Most NP events (124 of 132 (93.9%)) were classified as central nervous system manifestation, while only seven cases (5.3%) were classified as peripheral nervous system manifestation. The proportion of NPSLE events after having undergone re-evaluation was 28% (37 of 132 events) (figure 1). There was a tendency to overdiagnose NPSLE. Of the 69 events that were initially classified as NPSLE, only 23 (33.3%) were diagnosed as NPSLE after re-evaluation. There was a distinctive difference in the numbers of NPSLE at initial diagnosis and after re-evaluation (69 events vs 37 events).

Figure 1

Profile of neuropsychiatric manifestation before and after re-evaluation. NPSLE, neuropsychiatric SLE.

After re-evaluation, in the group with final diagnosis as non-NPSLE, 60 of 95 events (63.2%) were caused by aetiologies other than SLE. The most common other aetiology identified in this study was metabolic disorder (25%), whereas 36.8% of non-NPSLE cases resulted from undetermined aetiologies (online supplemental data). There were 82.8% (29 of 35 cases) of cases that did not have adequate supporting data to determine its attribution of the NP manifestation to SLE or other aetiologies.

Supplemental material

The most common symptom of NP in this study was headache (49 events), followed by seizures (20 events) and acute delirium syndrome (9 events) (figure 2). Of all these NP symptoms, the headache group had the most changes from NPSLE as initial diagnosis (30 events) to non-NPSLE after re-evaluation (19 events) (online supplemental data). On the other hand, in the cerebrovascular group, from eight non-NPSLE events, after re-evaluation, five events were concluded as NPSLE.

Figure 2

Neuropsychiatric syndrome after re-evaluation (non-NPSLE group includes undetermined events). GBS, Guillain-Barré syndrome; NPSLE, neuropsychiatric SLE.

There was no statistically significant difference in the subjects’ characteristics between the NPSLE and non-NPSLE patient groups after re-evaluation (table 1). Median (minimum–maximum) of SLE duration in the NPSLE patient group (6.5 months (0–168 months)) was shorter compared with non-NPSLE patient group (24 months (0–300 months)), but the result was not statistically significant.

Table 1

Characteristics of patients with neuropsychiatric (NP) manifestations

Almost all of the subjects in this study were on combination therapy, particularly in the NPSLE group. A history of pulse steroid use and immunosuppressant dose changes was more common in the NPSLE group than in the non-NPSLE group. The most common type of immunosuppressant used was mycophenolate mofetil (table 1).

Table 2 shows the comparison of clinical parameters between the NPSLE and the non-NPSLE groups after re-evaluation. MEX-SLEDAI score was significantly higher in the group with NPSLE events compared with the group with non-NPSLE events. Furthermore, active SLE (MEX-SLEDAI >5) had more tendency to develop NPSLE compared with inactive SLE (OR 2.64, 95% CI 1.1 to 6.1, p=0.02). Moreover, median ISR score was higher in the NPSLE group compared with the non-NPSLE group (OR 1.63, 95% CI 1.2 to 2.1, p<0.001) (table 2).

Table 2

Clinical characteristics of NPSLE and non-NPSLE groups after re-evaluation

There were 12 NP syndromes from our study (table 2), with headache (32.7% in NPSLE and 38.9% in non-NPSLE groups) as the most common clinical NP syndrome. The second most common symptom in the NPSLE group was cerebrovascular disease (18.9%), whereas in the non-NPSLE group was epileptic syndrome (13.3%). Both groups showed no significant diffrence in percentage of cognitive impairment or psychosis, and all of them had previously taken steroid medication. There were 12 cases that could not be classified according to ACR classification (1999) which were neuropathic pain (41.7%), conversion impairment (33.3%), vestibular syndrome (16.7%) and autonomic syndrome (8.3%).

In terms of the characteristics of diagnostic test results, the NPSLE group was more likely to have higher anti-double-stranded DNA (dsDNA) (median 317.3 (3.4–1438.4)), and lower C3 value (median 47 (12–148) mg/dL) and C4 value (median 8 (3–49) mg/dL) (table 3). However, there was no significant difference between the two groups in the positive antiphospholipid (aPL) status, median of erythrocyte sedimentation rate (ESR), median of C reactive protein (CRP) and the ratio of ESR/CRP >15. Of the 14 patients with NPSLE with a positive aPL, 3 people had a cerebrovascular disease and only 1 person received anticoagulant therapy. In the non-NPSLE group, 31 people tested positive for aPL, 3 people had a cerebrovascular disease and 2 people were on anticoagulation treatment.

Table 3

Comparison of laboratory test results between NPSLE and non-NPSLE groups

Among the cases with NP manifestation, lumbar puncture was performed in 16 out of 132 cases (12.1%). From the lumbar puncture data, the glucose in cerebrospinal fluid (CSF) was more likely to be lower in the non-NPSLE group (p=0.02). There was no significant difference in the other parameters of lumbar puncture result between the two groups (p>0.05) (table 3). Despite so, there was one case with myelopathy syndrome in which lumbar puncture was performed and high protein in the CSF was found (cells: 2, protein: 436 mg/dL).

Brain imaging was performed in 56.8% of cases (34 NPSLE cases and 41 non-NPSLE cases). An MRI brain scan with contrast was performed in 61.3% of cases (46 of 75), whereas MRI without contrast was performed in 10.6% of cases (8 of 75). CT brain imaging was also performed in which a CT scan with contrast was performed in 12% of cases (9 of 75) and a CT scan without contrast was performed in 16% of cases (12 of 75). From brain imaging results, a difference in the proportion of the abnormal results between NPSLE and non-NPSLE groups was found both in MRI and CT scans. From the MRI brain scan, a proportion of abnormal results in the NPSLE group accounted to 55.6% (18 of 27 cases), whereas in the non-NPSLE group 40% (12 of 27 cases). From CT brain scan results, a proportion of abnormal results in the NPSLE group accounted to 28.6% (2 of 7 cases), whereas in the non-NPSLE group accounted to 42.9% (6 of 14 cases). The most frequent pathological finding in this study was white matter hyperintensities followed by infarct. Other abnormal findings in this study were pathological enhancement, vasogenic oedema, sclerosis, encephalomalacia and extracranial tumour.

The undetermined case group consisted of the subgroups as follows: likely to be caused by NPSLE or likely to be caused by other aetiologies. NP manifestations were included in this group because both SLE disease activity and other comorbidities parameters were similarly not adequate enough to explain the aetiology of NP manifestations. Therefore, no conclusion could be made during re-evaluation. In this group, 34.4% of undetermined cases were caused by other aetiologies (online supplemental data), 28.6% cases were more inclined to NPSLE diagnosis and 37.1% did not have any tendency towards any aetiology due to the presence of external factors that obscure the clarity of its attribution to SLE.

When the undetermined case group was compared with the NPSLE group, the median MEX-SLEDAI score with NP manifestations was lower in the undetermined group compared with the NPSLE group. The proportion of active SLE was higher in the NPSLE group compared with the undetermined case group, but the difference was not statistically significant. Anti-dsDNA was significantly higher and C3 and C4 levels were significantly lower in the NPSLE group compared with the undetermined case group (table 4).

Table 4

Comparison of clinical parameters and laboratory test results between NPSLE and undetermined groups

Discussion

This study had recruited 94 subjects with SLE with a total of 132 cases with NP manifestation. Of all 132 cases, this study found 68.1% of subjects presented with a single NP manifestation, whereas 31.9% of subjects displayed multiple NP manifestations. This proportion of multiple NP manifestations is similar to the study conducted by Zhang et al.10 Higher proportion was found in other studies conducted by Hanly et al (40.3%) and Pawlak-Bus et al (53.8%).11 12 After having undergone thorough re-evaluation, the proportion of NPSLE cases from our study was 28% which is similar to the studies by Pawlak-Bus et al (23%, 34 of 143 cases) and Hanly et al (30.6%, 258 of 843 cases) despite the variability in population, location, facilities and study designs.11 12

The drastic change in the number of NPSLE cases as an initial diagnosis and NPSLE after re-evaluation shows a likelihood of overdiagnosis or underdiagnosis in some syndromes. This might be because the recommended and rapid diagnostic tests at the onset of the manifestation were not available. Also, not all NP manifestations were discussed by team which results in discrepancy between clinician judgement and the diagnosis.

We did not detect a significant difference in the demographic characteristics between NPSLE and non-NPSLE groups; however, the duration of the disease in the NPSLE group tends to be shorter. This contributes to the higher numerical score of ISR in the NPSLE group compared with the non-NPSLE group, particularly when NP manifestation presented in the first 6 months of SLE.13

In other studies, the predominant female gender was also found by Zhang et al, Hanly et al and Pawlak-Bus et al.10–12 Compared with the studies by Zhang et al and Pawlak-Bus et al, the median of age of the first SLE diagnosis and onset of NP manifestation was lower.10 12 This distinction may be caused by the variance in population.

In terms of organ involvement, half of the cases (53%) involve <2 organs. The most frequently involved organs are musculoskeletal, mucocutaneous, haematology and renal. No significant difference was found in the proportion of all organ involvements in NPSLE and non-NPSLE groups, unlike in Zhang et al’s study that found a significant difference in the organ involvement10 and Pawlak-Bus et al’s study that reported a significantly higher proportion in vasculitis involvement in the NPSLE group.12

High SLE disease activity is 2.6 times more likely to occur in the NPSLE than in the non-NPSLE group (OR 2.64 (1.1 to 6.1), p=0.036). Disease activity was measured using MEX-SLEDAI which is a recommended tool to evaluate SLE activity when immunological parameters are not available.9

The score of MEX-SLEDAI in the NPSLE group is likely to be higher than in the non-NPSLE group. Moreover, the wide variability of MEX-SLEDAI score in non-the NPSLE group might be due to the other aetiologies causing active SLE, hence creating an NP manifestation at the same time. Other studies by Zhang et al and Pawlak-Bus et al using SLEDAI and SLEDAI-2K to evaluate disease activity showed that both parameters were higher in the NPSLE group compared with the non-NPSLE group.10 12

We also found a significant difference in the median score of numerical ISR evaluated during multidisciplinary re-evaluation, which was 7 (3–10) in the NPSLE group and 6 (0–9) in the non-NPSLE group. The disadvantage of using this algorithm is that it does not take into account some possibly ambiguous conditions in clinical practice that may mask the NP manifestation such as COVID-19, severe electrolyte abnormality (sodium <115 mg/dL, serum calcium <5 mg/dL, serum magnesium <0.8 mg/dL), severe anaemia and hypertension crisis, thus increasing the score in some cases to more than 7 (NPSLE cut-off), even though they were considered as non-NPSLE during multidisciplinary re-evaluation.

Our study also identified central nervous system as the most frequent manifestation in NPSLE, which reaches 84.8% of all NP manifestations (91.9% in the NPSLE group and 83% in the non-NPSLE group). Nonetheless, only 12 of 19 clinical NP syndromes were identified (nine central nervous system and three peripheral nervous system manifestations). In addition, the only clinical syndrome that was significantly different between the NPSLE and the non-NPSLE groups was cerebrovascular disease. Psychosis was higher in the NPSLE group compared with the non-NPSLE group and headache and epilepsy were higher in the non-NPSLE group compared with the NPSLE group, but the results were not significantly different. Other NPSLE studies showed various proportions of NP syndrome, which might be related to the variance in population and study designs.14 15 Regarding the treatment, we are unable to analyse the association between cognitive impairment, psychosis or other NP syndromes and steroid use since nearly all subjects in both groups had taken steroids. In addition, the treatment data in this study are only limited to the time of data collection and not long-term data.

Peripheral nervous system manifestation in NPSLE barely occurs, which in this study was only found in 8.1% of cases. No mononeuropathy, plexopathy or autonomic impairment was reported. There was only one polyneuropathy case and one myasthenia gravis case that were considered as non-NPSLE, while there was one Guillain-Barré syndrome (GBS) that was considered as NPSLE after re-evaluation. Oomatia et al’s study reported peripheral neuropathy in 5.9% of patients with SLE (123 out of 2097 patients) with 66.7% associated with lower SLE disease activity and organ damage. However, the study was part of a long-term large-scale cohort study with a 25-year evaluation period. This explains the large number of peripheral neuropathy cases obtained.16 On the other hand, our study did not conduct long-term observations as supportive examinations of the peripheral nervous system were limited to electrodiagnostic testing. Skin biopsies were not performed, so no small fibre neuropathy was found. Additionally, another study also reported myasthenia gravis in NPSLE, but only about less than 1–2%.17

Among other NP manifestations, 80% cases (four of five cases) with neuropathic pain are classified as non-NPSLE due to the presence of degenerative spinal disease which was associated with one case of vestibular syndrome (benign paroxysmal positional vertigo).

This study also found a higher median value of dsDNA and lower C3 and C4 values in the NPSLE group, whereas no significant difference was detected in ESR and CRP. The proportion of ESR/CRP ratio >15 did not indicate any significant difference between NPSLE and non-NPSLE groups even though there is a tendency of higher proportion in the NPSLE group. This might be due to the low number of simultaneously performed ESR and CRP examination (of 18 cases in total, 4 NPSLE and 14 non-NPSLE cases), hence imprecisely affecting an interpretation of ESR/CRP ratio.

There is a significant difference in anti-dsDNA value between this study and Zhang et al’s study that may result from different anti-dsDNA grouping. Zhang et al’s study only grouped the value qualitatively into the positive anti-dsDNA which was high and slightly over normal.10 In addition, such difference is also found in ESR value. Even though there seems to be a distinction in ESR value between this study and Zhang et al’s study, overall, the ESR value tends to be similar. However, this might not indicate any significance due to the small size of the sample in this study.

aPL antibody positivity in this study is similar to other studies. It is well-known that cerebral infarction is a common complication in antiphospholipid syndrome (APS). Infarcts on brain imaging were also more common in patients with aPL-positive SLE (75% vs 53%) compared with APL-negative patients.18 Both positive and negative aPLs had similar rates of cerebrovascular disease, but there were too few cases for further analysis. Other studies have also found other factors that contribute to the incidence of thrombosis in SLE, such as smoking and disease activity other than APS.19

In this study, lumbar puncture was performed in 16 of 112 cases with NP manifestation (12.1%) and only in 124 cases with central nervous system manifestation (12.9%). The CSF glucose in the non-NPSLE group was likely to be lower, which might be due to the presence of neuroinfection as an aetiology in two non-NPSLE subjects. This suggests that lumbar puncture can benefit in diagnosing other NP manifestations such as GBS and myelopathy.

The studies regarding myelopathy SLE in CSF were mostly conducted in forms of serial cases or small scale with various results. Das et al’s study found a higher protein and pleocytosis in 50% of cases (10–40 cells) with high dsDNA (median 247 IU/mL (166.75–501.5)), C3 (median 47.5 mg/dL (22–62.75)) and C4 (median 9 mg/dL (3.38–10)) as the features of myelopathy SLE in CSF.20

In terms of brain imaging, previous studies found various MRI brain scan abnormalities in NPSLE such as atrophy, inflammation-like lesion, infarcts or demyelination.21 Other findings that lean towards small vessel disease such as hyperintense white matter lesions, atrophy, microbleed, lacunar infarct and/or large vessel disease were also reported in patients with NPSLE.22 This reveals similarities to this study’s finding.

This study confirmed limitations of a CT brain scan to detect abnormalities in NPSLE; therefore, CT scans performed in patients with NPSLE should focus more on excluding emergent neurological condition. In stable patients, MRI of the brain with contrast is preferable. Nonetheless, the main downside of an MRI brain scan is the long queue of the scheduled imaging, particularly in an outpatient setting.

The undetermined non-NPSLE group consisted of 35 cases that did not have any confirmed association with SLE. No significant differences in clinical factors and diagnostic test between NPSLE and undetermined groups were present. There is a likelihood of C3 value being lower in the NPSLE group, even though this was not significantly different.

Most cases in the undetermined group did not have complete data to conclude whether they were NPSLE or non-NPSLE due to several limitations such as financial limitation, long wait of diagnostic test result and high number of referral cases. In the conditions when such limitation exists, it is recommended evaluating the clinical NP manifestation at visit, previous therapy and its response, comorbidities that may result in NP syndrome and the trend of laboratory results before the onset of NP manifestation to consider the case as NPSLE or non-NPSLE. These components should be well recorded in medical records as baseline for the next follow-up.

This study is limited by incomplete data of laboratory results and brain imaging, disorganised documentation of NP manifestation reports, inadequate number of subjects with complete data and unbalanced number of subjects in the NPSLE and non-NPSLE groups. To overcome this limitation, it is recommended implementing total sampling, to extend the duration of discussion and not to exclude the subjects with incomplete diagnostic test results from re-evaluation. The multidisciplinary re-evaluation in this study was also only done by neurologists and clinical immunologists. Ideally, the re-evaluation should involve more disciplines. The cross-sectional design, with observations made only at the time of the most recent data collection and not over time, is another weakness of this study.

However, such limitation does not deter this study to inform the proportion of NPSLE and the comparison between NP manifestation in NPSLE and non-NPSLE. Nonetheless, further study still needs to focus more thoroughly on every clinical NP syndrome to portray the clinical characteristics of each syndrome in NPSLE more in depth.

In conclusion, NPSLE comprises a rather wide variability of syndromes; therefore, a consensus between clinicians has been the reference standard of NPSLE diagnosis. With various limitations in healthcare facilities, this hinders a precise accuracy in NPSLE diagnosis. One of the ways to overcome this obstacle is by performing multidisciplinary re-evaluation of NP manifestation in SLE. Thus, this study was conducted to highlight the importance of multidisciplinary re-evaluation of NP events along with addressing the differences across clinical and diagnostic test result characteristics between the NPSLE and non-NPSLE groups.

Data availability statement

Data are available upon reasonable request.

Ethics statements

Patient consent for publication

Ethics approval

This study involves human participants and was approved by the Ethics Committee of the Medicine Faculty, Universitas Indonesia, and the Research Committee of RSUPN Dr Cipto Mangunkusumo (KET-87/UN2.F1/ETIK/PPM.00.02/2023). Participants gave informed consent to participate in the study before taking part.

Acknowledgments

We thank all the patients with SLE and families, our neurology residents and all the nurses involved in the management of NPSLE cases in Dr Cipto Mangunkusumo Hospital, Jakarta.

References

Supplementary materials

  • Supplementary Data

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Footnotes

  • Contributors The study was designed by RE. The acquisition of data was performed by RE, SB, FO and AW. The interpretation and analysis of the data were performed by all authors. The work was drafted by RE. SB, as the guarantor, accepts full responsibility for the work and/or the conduct of the study, had access to the data and controlled the decision to publish. MHI, DI, KM, TA and DNL reviewed the manuscript. All authors critically reviewed or revised the manuscript, approved the submitted version and agree to be accountable for all aspects of the work.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.