Uncommon Presentation of Systemic Lupus Erythematosus: Intracranial Mass Lesions as the First Manifestation

Introduction

Systemic lupus erythematosus (SLE) is characterized by damage to organs and tissues caused by pathogenic autoantibodies and immune complexes. Neurological and psychiatric manifestations of SLE are collectively referred to as neuropsychiatric SLE (NPSLE) [1]. The typical initial symptoms of SLE are arthritis and dermatosis [2]. The reported prevalence of neuropsychiatric syndromes in SLE is approximately 56% [1], of which 6% to 12% occur in the first year of newly diagnosed SLE [3]. Approximately 20% of NPSLE cases present with neuropsychiatric symptoms as the first manifestation [4]. However, most brain magnetic resonance images do not show any abnormalities or only white matter hyperintensity or atrophy [4]. The most common brain magnetic resonance imaging (MRI) abnormality is cerebrovascular disease, accounting for approximately 8% of neuropsychiatric lupus cases [1]. Intracranial mass lesions are uncommon as the initial presentation of SLE, and these lesions can easily be mistaken for tumors or intracranial infections, thus delaying treatment. The diagnosis of SLE can be challenging, and no single clinical feature or lab abnormality can confirm SLE diagnosis [5]. The American College of Rheumatology (ACR) first developed the SLE classification criteria in 1971. These criteria were further revised by the Systemic Lupus International Collaborating Clinics (SLICC) group in 2012 [5]. In September 2019, the European League Against Rheumatism (EULAR) and the ACR published new criteria for the classification of SLE [5]. The EULAR/ACR-2019 criteria have a specificity of 93.4% and sensitivity of 96.1%, as opposed to the 83.7% specificity and 96.7% sensitivity of the 2012 SLICC classification criteria [5,6]. Here we report a case of a patient who presented with intracranial mass lesions as the first manifestation of SLE, and who was hospitalized twice. The final clinical diagnosis of SLE was made after careful exclusion of other diseases and consideration of the whole clinical presentation as well as serological and imaging tests.

Case Report

FIRST HOSPITALIZATION:

In August 2021, an 18-year-old woman was admitted to the hospital because of headache for 3 days, weakness in her left arm and blurred vision for 1 day. Before this sickness, she was in good health and denied any history of smoking or alcohol or substance abuse. There was no fever. Blood pressure was 94/63 mmHg, and left arm muscle strength was grade IV. Her electroencephalogram (EEG) showed slow and sustained activity on the right side, marked by delta waves (Figure 1A). MRI revealed multiple abnormal lesions in the right frontoparietal lobe (Figure 2A–2D). Magnetic resonance spectroscopy (MRS) did not show a tumor spectrum. No abnormalities were detected in the cerebrospinal fluid (CSF) by multiple laboratory tests, including routine, biochemical, culture, cytology, and second-generation sequencing virus tests. White blood cells, neutrophils, C-reactive protein (CRP), the treponema pallidum particle (TPPA), and syphilis antibodies by enzyme-linked immunosorbent assay (ELISA) were all negative. Mannitol and furosemide were administered to reduce intracranial pressure. After 20 days, the patient’s headache and muscle strength completely improved. A follow-up brain MRI revealed partially absorbed lesions with liquefied necrosis (Figure 2E–2H). MRS revealed a reduced N-acetyl-aspartate (NAA) peak and abnormal lactate peak, suggesting neuronal damage. Subsequently, the patient refused treatment and was discharged for follow-up.

SECOND HOSPITALIZATION:

One month after discharge, the patient was readmitted to the hospital due to symptoms including headache, fever (maximum 39°C), weakness of the right limbs, and aphasia for 1 day. Nervous system examination showed consciousness, mixed aphasia, right central facial paralysis, right limb muscle strength grade 0, left limb muscle strength grade III, and negative pathological signs. EEG showed continuous low voltage in the anterior head leads, most obviously on the right side (Figure 1B). No obvious abnormalities were found in computed tomography angiography and computed tomography venography of the head and neck (Figure 2L–2P). Brain MRI showed that, compared with the previous MRI, there were obvious and new abnormal signal shadows in the right parietal lobe and left frontotemporal and parieto-occipital lobes (Figure 2I–2K). These unique signal shadows may indicate inflammation, although antibody-mediated autoimmune encephalitis antibody testing in CSF revealed no significant findings. However, the patient tested positive for serum antinuclear antibodies at a dilution of 1: 1000, as well as anti-dsDNA, anti-SSA, and anti-ribosomal P protein antibodies. According to a repeat blood test, leukocytes (2.73×106 cells/L), hemoglobin (103 g/L), complement C3 (0.67 g/L) and complement C4 (0.12 g/L) were all decreased. The patient finally met guidelines developed by SLICC and EULAR/ACR indicating a diagnosis of NPSLE, following the exclusion of other potential diseases [5]. The SLE disease activity index (SLEDAI) score of 12 indicated active disease [7]. Dexamethasone 10 mg/d was prescribed, plus an appropriate amount of mannitol for intravenous infusion. The patient’s speech and limb muscle strength improved after 15 days. Brain MRI showed the smaller focus with signs of necrolysis and liquefaction (Figure 2M–2O), indicating the possibility of thrombosis or inflammation in small blood vessels, leading to tissue necrosis. After discharge, she started taking oral prednisone tablets (40 mg per day) and the dosage was gradually reduced during outpatient follow-up. No recurrence was found during 1 year of follow-up. She looks after herself and is now able to interact with people fluently.

Discussion

Neuropsychiatric complications can manifest at any point during the course of SLE, and may even be the initial presentation [4]. In cases where women of reproductive age have unexplained neurological complaints and cranial imaging shows mass lesions, a diagnosis should not be based solely on intracranial occupancy. To avoid treatment delays and rule out other possible disorders, it is critical to establish the diagnosis as soon as possible by testing for autoantibodies related to SLE. Our patient was admitted to the hospital due to non-specific manifestations such as recurring headaches and fever, as well as neurological manifestations such as limb weakness. Dynamic follow-up brain MRI showed that multiple space-occupying lesions involving both cerebral hemispheres appeared in a short period of time. After treatment, the space-occupying effect of the lesion gradually weakened. MRS found no tumor spectrum and no heterotypic cells were found in the CSF, thus ruling out the possibility of tumor. There was no significant increase in inflammatory markers in the blood, and no abnormalities were found in routine, biochemical, culture, and second-generation sequencing virus tests in the CSF. In addition, without anti-infective treatment, the patient’s symptoms improved, so intracranial infectious disease and infection-induced intracranial vasculitis were eliminated. For this patient, despite the lack of a brain biopsy, the combination of focal neurological symptoms, abnormal autoantibodies and positive response to immunotherapy strongly indicated a diagnosis of NPSLE. It is necessary to continue to follow up the patient in case of complications with other systemic injuries.

Both central (CNS) and peripheral (PNS) nervous systems may be involved in SLE in addition to several psychiatric manifestations, although the diagnosis can be difficult [8]. Currently, the diagnosis of SLE remains a clinical diagnosis [9]. Although new classification criteria including 2012 SLICC and EULAR/ ACR-2019 criteria are more sensitive, patients still experience diagnostic delays [5,9]. In 2023, a rare case of cerebral vasculitis mimicking a brain tumor in a woman with SLE was reported [10]. Despite a previous definitive diagnosis of lupus nephritis, this patient underwent a thorough work-up following the development of atypical neurological complications, and intracranial tumor-like manifestations were eventually attributed to SLE [10]. Our patient was different in that there was no previous history of lupus, which led to delayed screening for SLE and the initiation of immunotherapy without a clear basis for diagnosing tumor or infection.

The pathogenesis of neuropsychiatric events in lupus patients remains unclear, making diagnosis and treatment challenging. Complex mechanisms such as blood-brain barrier disruption, vascular occlusion, neuroendocrine immune imbalance, tissue and neuronal damage mediated by autoantibodies and inflammatory mediators, and direct neuronal cell death may be involved [11]. Focal neurological symptoms are more common in NPSLE patients because SLE is more prone to endothelial dysfunction caused by autoimmune or ischemic complications, including vasculitis and thrombosis [12]. For active neuropsychiatric disease caused by SLE, it is recommended to consider glucocorticoids and immunosuppressants to treat inflammatory manifestations. In addition, the use of antiplatelet agents/anticoagulants is recommended for atherothrombosis/ antiphospholipid antibody-related manifestations [9]. For patients who achieve long-term remission, consider tapering the corticosteroid dose. There is no doubt that SLE requires multi-disciplinary, individualized management, including patient education and shared decision-making, taking into account costs to the patient and society [9].

Conclusions

It is uncommon for SLE to present with intracranial mass lesions as the initial presentation. When mass lesions of the brain occur rapidly in young adults, inflammatory lesions such as SLE should also be taken into account in addition to considering tumors, especially metastatic tumors. The pathogenesis of neurological symptoms in SLE patients may involve thrombosis or vasculitis leading to cerebral necrosis. Early initiation of immunotherapy and personalized management can improve prognosis in these cases.