Rheumatoid Meningitis Research Articles

Rheumatoid meningitis sine arthritis: An emerging cause of isolated pachymeningitis and leptomeningitis with typical features

Background and purposeRheumatoid meningitis (RM) is a meningeal inflammation rarely occurring during the course of rheumatoid arthritis (RA). Anti-citrullinated protein antibodies (ACPA), which are highly specific biomarkers of RA, may allow RM sine arthritis (RMSA) to be diagnosed as an extra-articular early lesion of RA. MRI typically displays pachymeningitis and/or leptomeningitis predating convexity, and CSF diffusivity is focally restricted. Blood ACPA is a strong clue and intrathecal synthesis of ACPA is characteristic although rarely reported. MethodsWe report two cases of RMSA that were confirmed by meningeal biopsy and intrathecal synthesis. ResultsRMSA abated after steroids alone or associated with rituximab. No arthritis occurred during the follow-up. ConclusionRM can occur in the absence of RA.

Rheumatoid meningitis: a case series report and review of modern therapeutic schemes and outcome.

Rheumatoid meningitis (RM) is an extremely rare extra-articular complication of rheumatoid arthritis (RA), with approximately 165 cases reported world-wide. RM exhibits a broad range of symptoms, with stroke-like episodes and seizures being the most common manifestations. The primary differential diagnoses include vascular and infectious diseases. The influence of immunomodulatory medications on the pathophysiology of RM remains unclear. There are no consensus guidelines on therapeutic regimen. We present four patients with prior history of RA that developed different neurological syndromes in correlation to radiological leptomeningitis. Clinical presentations, comorbid conditions, supplementary diagnostic assessments, treatments, and prognosis are provided. A literature review of recent immunosuppressive management in RM patients was performed. Three patients presented to hospital with recurrent focal seizures. Only two suffered meningism, reporting headache and fever. Magnetic resonance imaging (MRI) showed different grades of leptomeningitis across all cases. Notably, three cases demonstrated bilateral involvement extending to the pachymeninges. Two patients exhibited pronounced CSF mononuclear inflammation while extended microbiological evaluations yielded negative results. Two patients required biopsy for confirmation. The initiation of immunosuppressive therapy marked a turning point for three patients who previously exhibited progressive deterioration. Mortality was absent in all cases. Our experience remarks the elusive nature of RM. Rigorous exclusionary diagnostics are imperative to differentiate RM from mimicking conditions. Clinical manifestations oscillate between transient episodes and progressive neurological impairments, punctuated by frequent epileptic seizures. In scenarios where clinical worsening persists or where clinical and radiological evaluations are inconclusive, aggressive immunosuppressive therapy is recommended.

Rheumatoid meningitis in the absence of rheumatoid arthritis: 2 cases

Rheumatoid meningitis (RM) is a rare extra-articular manifestation of rheumatoid arthritis (RA) that has been increasingly recognized by neurologists. However, the diversity of its clinical manifestations makes its diagnosis difficult. RM does not have a unified diagnostic standard, and its link with RA needs to be studied further. Here we report two cases of RM without a history of RA. The first patient, an 80-year-old woman, presented with sudden unilateral limb weakness, with brain MR showing abnormal signals in the leptomeningeal of the right frontal parietal. Subarachnoid hemorrhage was excluded after imaging examination, and infectious meningitis was ruled out after cerebrospinal fluid (CSF) examination. The patient was diagnosed as having RM, she had increased levels of CCP and AKA, the markers of RA, but no history of the disease or other clinical manifestations of it. Another case, a 65-year-old man, was hospitalized with Bell’s palsy. We found that he had intracranial imaging changes highly consistent with those characteristic of RM during his routine examination. Except for the left peripheral facial palsy, the patient had no other neurological signs or symptoms and no RA history. After a careful physical examination, we found no joint or other manifestations or serological abnormalities consistent with RA (RF, CCP, AKA, etc.). However, after excluding infection meningitis and considering the patient’s unique imaging results, we diagnosed him as having RM. We report these two cases as references for clinical diagnosis and treatment of RM, providing a discussion of our rationale.

Radiological insights into rheumatoid meningitis - a rare central nervous system manifestation of rheumatoid arthritis: a retrospective review of six cases.

The objective is to analyze and review the clinical, laboratory, and neuroimaging characteristics of rheumatoid meningitis (RM) in six patients with known rheumatoid arthritis (RA). We performed a retrospective review of patients diagnosed with RM from August 2012 to June 2023. To identify the cases, we used medical term search engines and the hospital´s radiology case database. Clinical information and laboratory findings were gathered from the medical records. A neuroradiologist with five years of experience reviewed and analyzed the RM to determine the characteristics findings of RM. Six patients with RM are included. Seizures along with headaches were among the clinical signs that were documented. All the patients had high levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptides (ACPA) in the peripheral blood. Biopsy in two cases confirmed typical rheumatoid nodules. Leptomeningeal enhancement was found bilaterally in all cases and was predominantly found in the frontoparietal region. "Mismatch DWI/FLAIR" was found in five patients. Bilateral subdural collections could be found in two patients. Brain PET scan revealed increased metabolism in two cases. Rheumatoid meningitis is a rare complication of rheumatoid arthritis (RA) with challenging clinical diagnosis due to non-specific symptoms. This study highlights the importance of MR in detecting characteristic neuroimaging patterns, including "mismatch DWI/FLAIR", to aid in early diagnosis. Increased awareness of this condition may facilitate timely intervention and improve prognosis. These results still need to be verified by large studies.

Three-year follow-up of rheumatoid meningitis with matrix metalloprotease-9 levels in the serum and cerebrospinal fluid as indicators of disease activity: A case report

Rheumatoid meningitis (RM) is an extra-articular complication of rheumatoid arthritis (RA). Although reports of RM sine arthritis exist, most patients with this presentation were diagnosed with RA within one year of RM onset. There are no established biomarkers reflecting the disease activity of RM. This case report highlights the elevation of matrix metalloprotease (MMP)-9 levels during the acute phase of RM and decline during remission. Additionally, this is the first case report of RA diagnosed three years after the onset of RM. It is important to further validate the utility of MMP-9 and conduct long-term follow-up of RM sine arthritis.

A Case Report of Rheumatoid Meningitis – A Rare Condition Presenting with Neurological Deficits

Rheumatoid meningitis (RM) is a rare condition seen in patients with longstanding rheumatoid arthritis (RA). It can present with a variety of neurological symptoms and is often mistaken for other neurological conditions, especially in the setting of immune suppression in these patients. We present a rare case of RM in an elderly woman with RA that presented with focal neurological symptoms and was eventually diagnosed on brain biopsy. Our case serves to highlight the diagnostic dilemmas faced while evaluating and treating patients presenting with such an exceedingly rare condition and the importance of multidisciplinary collaboration in the management of such complex patients.

OA17 Rheumatoid meningitis - a rare complication of rheumatoid arthritis

Abstract Introduction A wide spectrum of neurological complications can occur in rheumatoid arthritis (RA) including peripheral neuropathy, mononeuritis multiplex and rheumatoid vasculitis. Cerebrovascular disease is also common. We describe a rare neurological complication of RA. Case description The patient was first diagnosed with seropositive RA in 2015 at the age of 68. His rheumatoid factor at presentation was 144 kIU/L and CCP antibodies >340 U/mL. His background include alcohol excess and obstructive sleep apnoea with peripheral neuropathy attributed to alcohol. Nerve conduction studies demonstrated axonal neuropathy. By 2016, he had achieved good disease control with combination methotrexate and sulfasalazine. In 2018, he was admitted to stroke services with right arm weakness and focal neurological deficit on examination. An urgent CT head showed possible right parietal extra dural haemmorhage. His CRP was <5, ESR 24 with a normal ANA. Borrelia, syphilis and HIV screening were normal. Anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Hu, anti-Yo and anti-Ri antibodies were all negative. Lumbar puncture revealed a normal glucose and red blood cells count but the CSF protein was raised at 851 mg/L with a lymphocyte count of 9/ul. Gram stain, culture, viral PCR for HSV, VZV, enterovirus, parechovirus and adenovirus were normal and CSF cytology demonstrated a lymphocyte pleocytosis. Subsequent contrast MRI head scan showed leptomeningeal enhancement with gadolinium contrast. MRI of the cervical spine and brachial plexus was normal and an EMG/NCS of the upper limb demonstrated an incidental ulnar nerve compression at the elbow. Following neurology input, the leptomeningeal enhancement was thought to represent rheumatoid meningitis (RM). He was treated with 1 mg/kg prednisolone and rituximab with prompt and complete recovery. He remains well from both the perspective of his RA and RM. Discussion RM is a rare form of aseptic meningitis. Aseptic meningitis is commonly defined as clinical and CSF evidence of meningeal inflammation in the absence of an infectious aetiology. The vast differential includes malignancies, drug-induced and autoimmune diseases, for example lupus and sarcoidosis. The diagnosis of RM requires a high index of suspicion as well as exclusion of other causes. Historically RM was diagnosed at post-mortem but MRI scanning means pre-mortem diagnosis is possible. It is considered rare but serious manifestation of RA. Case reports suggest RM usually occurs in those with long standing seropositive RA but RM has been described in the early stages of RA and even as a presenting feature. Peripheral disease activity does not correlate with occurrence of RM. The clinical presentations vary depending on the brain structure involved and can include motor or sensory deficits, cognitive disturbance and seizures. It may mimic many other conditions. Radiological findings will not distinguish RM from other causes of aseptic meningitis. CSF finding of lymphocytosis and rheumatoid factor (if available) may help distinguish RM from other causes. Meningeal biopsy can confirm the diagnosis. Due to the rarity of RM, there are no current guidelines on treatment. Historically, corticosteroids are the main induction agent. There are case reports highlighting possible success from the addition of cyclophosphamide and rituximab. Case series also highlight a significant mortality rate in excess of 60% even despite treatment. This may represent publication and historical bias. Key learning points Rheumatoid meningitis (RM) is a rare but serious complication of rheumatoid arthritis. RM may not correlate with disease activity nor disease duration. Diagnosis is a challenge due to its wide clinical phenotype as well as the non-specificity of imaging, lumbar puncture and serological findings. Treatment options are based on case reports and series and include corticosteroids, rituximab and cyclophosphamide.

Rheumatoid meningitis: a rare neurological complication of rheumatoid arthritis.

To describe the clinical and neuroimaging characteristics of rheumatoid meningitis (RM) in Chinese patients. The patients admitted to our hospital with the diagnosis of RM in the past 8 years were retrospectively analyzed. Six patients with RM were identified among 933 patients admitted with rheumatoid arthritis (RA). The symptoms of meningitis occurred after onset of arthritis in five patients and before onset in one. Headache (n=6), hyperacute focal neurological deficits (n=4) and seizures (n=3) were the most prevalent symptoms. The nadir modified Rankin Scale score was ≥3 in five patients. Rheumatoid factor was elevated in all patients, and interleukin-6 levels in cerebrospinal fluid were dramatically elevated in three of four tested patients. Magnetic resonance imaging of the brain revealed that the meninges were affected in all patients and the cerebral parenchyma was affected in one patient. The lesions were generally located in the frontoparietal region and showed restricted diffusion along the adjacent subarachnoid space. RM occurred during disease-modifying therapy in four patients. In the acute episode, three patients improved on tocilizumab and the other three improved on pulse corticosteroids. For maintenance therapy, two patients received combined therapy of tocilizumab and other immunosuppressive agents, one received adalimumab and methotrexate, and two received low-dose oral corticosteroids with an immunosuppressive agent. Five patients had a good outcome, and one died of Pneumocystis jirovecii pneumonia after stabilization of his neurologic conditions. No relapse of RM occurred on immunotherapy during follow-up. Chinese patients with RM share some remarkable clinical and neuroimaging features and respond well to appropriate immunotherapy. Tocilizumab could be a treatment option for this severe complication of RA.

A Rare Case of Rheumatoid Meningitis (P9-5.024)

<h3>Objective:</h3> To increase awareness of this rare and underrecognized form of aseptic meningitis. <h3>Background:</h3> Rheumatoid meningitis (RM) is a rare disorder that is historically difficult to diagnose given its diverse range of reported clinical presentations and lack of clear pathognomonic findings. RM is typically a diagnosis of exclusion, made only after ruling out alternative infectious and malignant disease. Common laboratory findings include elevated rheumatoid factor (RF) and anti-citrullinated peptide (anti-CCP) antibody. MRI may show leptomeningeal or pachymeningeal involvement, primarily in a frontoparietal location pattern. CSF analysis typically reveals a pleocytosis with a moderate elevation in protein level. Treatment generally consists of high dose steroids followed by immunotherapy. <h3>Design/Methods:</h3> A 69-year-old male with a history of longstanding rheumatoid arthritis on immunosuppressive therapy with methotrexate and recent addition of abatacept presented to our tertiary referral center with progressive neurologic deficits. He initially developed sudden, bilateral sensorineural hearing loss and dizziness with reported normal brain imaging. Six months later, he developed seizures and rapid functional decline with severe cognitive impairment. <h3>Results:</h3> An MRI brain revealed multifocal leptomeningeal and pachymeningeal enhancement with a relatively unremarkable appearance of the subjacent parenchyma, primarily focused in the right frontoparietal region. CSF studies were remarkable for a mild pleocytosis and a moderate elevation in CSF protein. RF was markedly elevated at 227 IU/mL as was anti-CCP antibody at &gt;200 units. Extensive serum and CSF infectious and oncologic testing were negative. He was treated with 5 days of IV methylprednisolone with a rapid improvement in his cognition. Alternative immunosuppressive therapy for RA with methotrexate and rituximab has resulted in sustained functional stability. <h3>Conclusions:</h3> While rare, RM should be considered in the differential of a patient with aseptic meningitis of unclear etiology, with or without a history of rheumatoid arthritis. Early detection and treatment are essential to the prevention of long-lasting sequela of the disease. <b>Disclosure:</b> Dr. Schmoll has nothing to disclose. Dr. Rodenbeck has nothing to disclose. Dr. Graner has nothing to disclose.

A review of rheumatoid meningitis with case studies.

Rheumatoid arthritis (RA) is an autoimmune disease involving synovial joints, and it is known that extra-articular manifestations that may affect the central and peripheral nervous systems may develop during its course. Rheumatoid meningitis is very rare among all neurological involvements. In this study, cases diagnosed as rheumatoid meningitis with clinical, imaging, laboratory, and histopathological features are presented, and the aim of the study is to present current approaches in the diagnosis and treatment of rheumatoid meningitis in the light of case studies and current literature. The data of the patients who were followed up with the diagnosis of rheumatoid meningitis in neurology clinic between 2017 and 2021 were reviewed retrospectively. Three cases diagnosed with rheumatoid meningitis are presented in detail. In the first case, the diagnosis was reached by clinical, imaging, and laboratory findings as well as treatment response, while the diagnosis was made by histopathological verification in the second case. The third case shows that spontaneous remission can be observed in the course of rheumatoid meningitis. Rheumatoid meningitis, which is one of the rarest involvements in the course of RA, may present with headaches, focal neurological deficits, seizures, and altered consciousness. A meningeal biopsy is recommended when the differential diagnosis cannot be ruled out with imaging and laboratory findings. In the differential diagnosis Mucobacterium tuberculosis, syphilis, neuro-sarcoidosis, immunoglobulin G4-related disease, lymphoproliferative diseases, and systemic metastasis should be kept in mind. Aggressive RA management is recommended for treatment.

Anti-Cyclic Citrullinated Peptide Antibody Index in the Cerebrospinal Fluid for the Diagnosis and Monitoring of Rheumatoid Meningitis.

Rheumatoid meningitis (RM) is a rare but often aggressive neurological complication of rheumatoid arthritis. The diagnosis of RM, besides the clinical, radiological, and laboratory criteria, usually requires a cerebral biopsy. Based on the two cases presented in this paper, we propose a new laboratory marker. Cerebrospinal fluid and serum anti-cyclic citrullinated peptide (CCP) IgG were measured, and the intrathecal synthesis of anti-CCP antibodies (anti-CCP antibody index) was calculated using the hyperbolic function. The anti-CCP antibody index was positive in both cases at first diagnosis and progressively decreased after treatments. Together with clinical and radiological criteria, the calculation of the anti-CCP intrathecal synthesis, more than the simple measurement of serum or cerebrospinal fluid anti-CCP antibody titers, may represent a useful tool for RM diagnosis and, possibly, for treatment response.

A Case of Rheumatoid Meningitis

Rheumatoid meningitis, a very rare complication, is not well-recognised, and there are few reports describing its treatment. We report the case of a 74-year-old Japanese woman who was diagnosed with rheumatoid meningitis by characteristic brain magnetic resonance imaging (MRI) and was successfully treated with glucocorticoids. We observed fluid-attenuated inversion recovery and diffusion-weighted imaging hyperintensity, which had a meningeal gadolinium-enhancing characteristic of rheumatoid meningitis. We suggest that it is possible to diagnose this disease based on characteristic MRI findings and treat patients early using glucocorticoids.

Editors' Note: Teaching NeuroImage: Palindromic Rheumatoid Meningitis: A Tale of 2 Hemispheres

In “Teaching Neuroimage: Palindromic Rheumatoid Meningitis: A Tale of 2 Hemispheres,” Itrat et al. demonstrated MRI findings due to palindromic rheumatism in a patient who initially had isolated right-sided cortical hyperintensities/enhancement in 2004 and then had isolated left-sided cortical hyperintensities/enhancement in 2016. They describe the enhancement pattern as “pachymeningeal.” Hung notes that the term “pachymeningeal” should be used to describe enhancement of the dura and that the pattern of enhancement in these MRIs should be described as “leptomeningeal” because it follows the pial surface of the brain and fills the subarachnoid spaces. Itrat agreed that the published images show leptomeningeal enhancement but noted that the patient also had pachymeningeal enhancement in images not included in their publication. In “Teaching Neuroimage: Palindromic Rheumatoid Meningitis: A Tale of 2 Hemispheres,” Itrat et al. demonstrated MRI findings due to palindromic rheumatism in a patient who initially had isolated right-sided cortical hyperintensities/enhancement in 2004 and then had isolated left-sided cortical hyperintensities/enhancement in 2016. They describe the enhancement pattern as “pachymeningeal.” Hung notes that the term “pachymeningeal” should be used to describe enhancement of the dura and that the pattern of enhancement in these MRIs should be described as “leptomeningeal” because it follows the pial surface of the brain and fills the subarachnoid spaces. Itrat agreed that the published images show leptomeningeal enhancement but noted that the patient also had pachymeningeal enhancement in images not included in their publication.

Rheumatoid Meningitis as an Extra-articular Manifestation of Rheumatoid Arthritis.

Rheumatoid Meningitis as an Extra-articular Manifestation of Rheumatoid Arthritis.

Unilateral rheumatoid meningitis presenting with headache in a patient with absent history of rheumatoid arthritis

Rheumatoid arthritis is a chronic systemic autoimmune disorder, leading to joints` inflammation and their destruction. Extra articular manifestations are described in about 20% of patients with rheumatoid arthritis. Rheumatoid meningitis (RM) is a very rare severe complication with CNS involvement. The severity and lethality of rheumatoid meningitis is determined by its challenging diagnosing due to multiplicity of clinical symptoms and takes 60% by Mélanie Trabelsi et al., in spite of treatment.

Rheumatoid meningitis: A systematic review and meta-analysis.

Rheumatoid meningitis (RM) is a neurological complication of rheumatoid arthritis (RA). Current evidence is based on case reports and partial reviews. This is a systematic review and meta-analysis following the PRISMA statement. The aim is to describe the characteristics of the disease, including clinical, imaging and laboratory findings, treatment, outcomes and prognosis reported in the literature. In all, 103 studies with 130 cases were included. RM affected adults with an average age of 62years, with or without a previous RA diagnosis. RA activity and time with the disease were associated with a worse prognosis. Most common clinical manifestations were transient focal neurological signs (64.6%), systemic symptoms (51.3%), episodic headache (50.4%) and neuropsychiatric alterations (47.7%). Joint manifestations were present in only 27.4% of cases. Brain magnetic resonance imaging showed unilateral or bilateral involvement, predominantly frontoparietal. Both pachymeninges and leptomeninges were affected, the latter more frequently (82.88%). The laboratory findings included increased levels of rheumatoid factor (89.71%), anti-cyclic citrullinated peptide (89.47%), C-reactive protein (82.54%) and erythrocyte sedimentation rate (81.81%). Cerebrospinal fluid analysis showed an increase in the protein level (76.14%), with pleocytosis (85.19%) of mononuclear predominance (89.19%). Biopsy was performed in 72.52% of the patients. Corticosteroid pulse therapy was the main induction therapy. Disease relapse occurred in 31.17% of patients, whilst 54.54% had a full recovery. Rheumatoid meningitis must be considered in adult patients with or without RA diagnosis, high-dose corticosteroid induction therapy should be installed and maintenance therapy plays a key role. It is not recommended to use anti-TNF as an induction therapy. Nowadays, RM has a significantly better outcome. These findings may aid clinicians in timely RM diagnosis and treatment, thus improving its outcomes.

Teaching NeuroImage: Palindromic Rheumatoid Meningitis: A Tale of 2 Hemispheres

A 61-year-old man presented with right-sided somatosensory seizures and evidence of left-sided pachymeningeal enhancement on a cerebral MRI (figure, A–C). The patient had a seizure 12 years prior. Upon review of the previous MRI, similar inflammatory changes in the contralateral hemisphere were seen (figure, D–E). Serologic and cerebrospinal fluid analysis and a brain PET scan demonstrated no abnormality. Brain biopsy revealed chronic lymphohistiocytic meningitis. His episodic arthropathy prompted rheumatological workup that revealed elevated cyclic citrullinated peptide and rheumatoid factor, suggestive of palindromic rheumatism, with corresponding imaging findings reminiscent of those described with rheumatoid meningitis.1,2 He improved after a brief course of steroids with resolution of meningeal enhancement (figure, F).

A case of rheumatoid meningitis with elevated antibody titer indices of anti‐cyclic citrullinated peptide antibody and anti‐galactose‐deficient IgG antibody

AbstractRheumatoid meningitis (RM) is a rare central nervous system manifestation of rheumatoid arthritis (RA). A meningeal biopsy is useful for diagnosis but is invasive and not very sensitive. We report about a patient with RM who was diagnosed using indices of anti‐cyclic citrullinated peptide (CCP) antibody and anti‐galactose‐deficient IgG antibody (carbohydrate in rheumatoid factor [CARF]) and who had refused to undergo biopsy. The patient's antibody titer indices of anti‐CCP antibody and CARF were 21.01 and 4.44, respectively. The patient's symptoms and abnormalities on brain magnetic resonance imaging improved after steroid therapy. Antibody titer indices of the anti‐CCP antibody and CARF can be used to diagnose RM in cases where biopsy is unavailable.

Rheumatoid Meningitis

Rheumatoid meningitis, a central nervous system complication of rheumatoid arthritis, has low morbidity but poor prognosis without treatment. Contrast-enhanced meningeal lesions on one side of the brain on MRI and hyperintensity of the pia mater on FLAIR image are characteristic features and should trigger the suspicion of rheumatoid meningitis. Steroids are effective for treatment, and good outcomes can be obtained through early diagnosis and intervention.

Aseptic meningitis in rheumatoid arthritis after anti-TNF administration: a case-based literature review

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular and extra-articular manifestations. Among extra-articular involvement, rheumatoid meningitis (RM) is a rare condition, which may exhibit variable symptoms including headache, focal and/or generalized neurologic deficits. It may develop as the preceding manifestation of RA or occur at any time of the disease course. Some drugs used for the treatment of RA may give rise to aseptic meningitis or create a tendency to infectious meningitis due to their immunosuppressive effect. All these possibilities may lead to difficulties in the differential diagnosis. Achieving a diagnosis in a short time is crucial in terms of prognosis. Here, we would like to report a case with longstanding RA manifested by left-sided weakness and seizure shortly after initiating etanercept (ETA) therapy. ETA-induced meningitis was confirmed with appropriate diagnostic tools. Our aim with this case-based review is to attract the attention of this rare condition and discuss diagnostic challenges.