Rare disease
CASE REPORT
Rheumatoid meningitis: a rare complication of rheumatoid arthritis Lin Lu,1,2 Bart Chwalisz,3 Rolf Pfannl,4 Pushpa Narayanaswami3 1
School of Medicine, Imperial College London, London, Greater London, UK 2 William Harvey Hospital, Ashford, Kent, UK 3 Department of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA 4 Department of Pathology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA Correspondence to Dr Lin Lu, [email protected] Accepted 8 June 2015
SUMMARY We present a case of a 60-year-old Caucasian woman with a 23-year history of rheumatoid arthritis, who presented with a 2-week history of headache and cognitive/behavioural changes. On the basis of clinical features, radiology, laboratory data and meningeal biopsy, a diagnosis of rheumatoid meningitis was performed. High-dose intravenous methylprednisolone was used as initial treatment followed by oral prednisone. The patient’s symptoms improved and repeat MRI scans confirmed resolution of the meningeal lesions. The clinical diagnosis of rheumatoid meningitis is difficult, but it must be considered in patients with longstanding rheumatoid arthritis presenting with neurological symptoms. Glucocorticoids or other immunomodulatory therapy are the mainstay of treatment.
affect, pressured speech, flight of ideas, paranoia, disorganised thoughts, inattention, perseveration and poor short-term memory without focal sensory or motor deficits. Rheumatology review detected no acute joint inflammations, no rheumatoid nodules and no extra-articular manifestations of RA. There were no features of destructive arthritis on the X-rays of the hands. An X-ray of the right foot showed narrowed joint spaces between the first interphalangeal and fifth metatarsophalangeal joints, and mild joint subluxation at the third proximal interphalangeal joint without clear features of erosions. The X-ray of the left foot demonstrated narrowed third and fifth metatarsophalangeal joint spaces with erosive changes. These findings were consistent with inflammatory arthropathy.
INVESTIGATIONS BACKGROUND Rheumatoid meningitis (RM) is a rare manifestation of rheumatoid arthritis (RA). The non-specific clinical presentations of RM make its diagnosis difficult, and diagnosis is based on a combination of clinical, radiological and histopathological features. Prompt treatment is critical due to the high mortality rate of untreated RM. No standardised treatment regimen has been established but steroids and steroid-sparing immunosuppressive agents have both been used.
CASE PRESENTATION
To cite: Lu L, Chwalisz B, Pfannl R, et al. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2014208745
A 60-year-old Caucasian woman with a 23-year history of seropositive RA, on auranofin and prednisone, was admitted to an outside hospital for acute-onset frontal headache, photophobia and chills 6 days following a tooth extraction. Head CT at the time of presentation showed only microvascular disease. She had insomnia and multiple ‘panic attacks’ during her first admission. Symptoms resolved with tramadol and lorazepam. She was diagnosed with panic disorder and was discharged home 5 days later. Over the following 2 weeks, she developed symptoms of mania and delirium, with impaired shortterm memory and visual hallucinations, and was admitted to our hospital. Aside from the medical history of RA resistant to treatment with diseasemodifying antirheumatic drugs, she also had a history of positive PPD ( purified protein derivative) (tuberculosis/TB skin test). On examination, the patient was dishevelled and agitated; there was no fever or meningismus. Neurological examination demonstrated labile
Routine blood tests revealed an elevated white cell count (WCC) 18.6×109/L (neutrophils 66.5%), minimally raised C reactive protein (CRP) 7 mg/L (normal 0–5 mg/L) and erythrocyte sedimentation rate (ESR) was mildly elevated at 31 (normal 0–20 mm/h). Rheumatoid factor (RF) titre was >1:160 and cyclic citrullinated peptide antibody (anti-CCP) was strongly positive; other autoimmune work up was negative (antinuclear antibody, antidouble-stranded DNA, anti-Smith, antiribonucleoprotein, anti-Ro/La, thyroid peroxidase antibodies and paraneoplastic panel including antivoltage-gated potassium channel antibody). Quantiferon Gold test for TB was positive. Blood and urine bacterial cultures, serum and urine toxicology screens, and HIV and syphilis testing were negative. Cerebrospinal fluid (CSF) revealed: two WCCs (lymphocytes), three red blood cells, normal glucose (58 mg/dL) and normal protein (26 mg/dL); CSF Cryptococcus antigen, rapid plasma reagin, bacterial and fungal cultures, herpes simplex PCR and arbovirus panel were negative. MRI of the brain with gadolinium contrast revealed pachymeningeal and leptomeningeal enhancement along the left frontal and temporal lobes, with an area of adjacent parenchymal FLAIR (fluid attenuation inversion recovery) signal abnormality (figure 1A, B). EEG showed generalised slowing, most prominent over the left frontal area. CT of the torso did not reveal any systemic abnormality. Bone marrow immunophenotyping showed a non-specific T-cell-dominant lymphoid profile without clonal proliferation.
DIFFERENTIAL DIAGNOSIS The initial diagnosis was mania secondary to an organic aetiology, with speculation of possible
Lu L, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208745
1
Rare disease
Figure 1 Brain MRI with gadolinium. Axial and coronal T-1 postgadolinium brain MRI 3 weeks after symptom onset revealing abnormal pachymeningeal and sulcal enhancement along the left frontal and parietal lobes (arrows, A and B). There is resolution of the enhancement after 8 weeks of treatment with corticosteroids (arrows, C and D). Evidence of craniotomy for the brain biopsy is noted in D. infectious causes such as brain abscess, given the recent tooth extraction history; RM was considered a clinical diagnosis of exclusion. Treatment was initiated with empirical antibiotics and antiviral agents (vancomycin, ceftriaxone, metronidazole and acyclovir). Haloperidol and valproic acid were used for the behavioural symptoms, without much improvement. The patient developed partial complex seizures during her stay, despite adequate levels of valproic acid; they were controlled with the addition of phenytoin. Given the normal blood results, negative cultures/viral studies, lack of response to antibiotics and no evidence for systemic malignancy, infectious and neoplastic causes of meningitis were considered unlikely. This lack of an infectious cause of aetiology was further demonstrated by the normal CSF cell count and protein level. A left frontal meningeal biopsy was performed. On inspection, the dura was thickened, yellow and covered with friable granular tissue; the brain itself appeared intact. Histopathology revealed diffuse infiltration by lymphocytes, 2
histiocytes, plasma cells and multinucleated giant cells (figure 2). There were numerous granulomas with focal central necrosis. Fungal, treponemal and acid-fast bacilli stains were negative. The histopathological findings were felt to be consistent with rheumatoid or infectious pachymeningitis. Bacterial, fungal and acid-fast cultures were negative. TB-specific and general mycobacterial tissue PCR studies were negative, making tuberculous pachymeningitis unlikely. Therefore a diagnosis of granulomatous meningitis secondary to the RA was performed.
TREATMENT We treated this patient with intravenous pulse steroids (methylprednisolone 1000 mg daily for 5 days), followed by prednisone 60 mg tapered over several months.
OUTCOME AND FOLLOW-UP The patient had near-complete improvement in her symptoms after completing high-dose corticosteroids, with minimal residual Lu L, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208745
Rare disease
Figure 2 Histopathology (H&E stain) of the meningeal biopsy. Granulomatous meningitis with diffuse, deep infiltration of the dura by inflammatory cells (A, magnification ×40); higher power view (B, magnification ×100) showing lymphocytes, plasma cells and scattered histiocytic granulomas with multinucleated giant cells. Some granulomas reveal central necrosis (C, ×100). Multinucleated giant cells are clearly seen (D, ×200). memory impairment. Repeat blood tests showed that CRP had gone up further to 9.7 mg/L, but decreased to a normal level of 3.6 mg/L within a week of methylprednisolone administration, and had remained in the normal range since. ESR had also increased further to 56 mm/h during the patient’s hospital admission, but following the initiation of methylprednisolone it reduced to 35 mm/h and later to 0 mm/h 6 weeks post-steroid use, and subsequently remained normal. The elevated WCC at presentation was thought to be caused by the patient’s chronic steroid use before her hospital admission; the WCC increased further to 25×109/L after highdose steroids and has subsequently remained high normal/mildly elevated, ranging between 8.1 and 17.8×109/L. This is likely due to the very slow, extended steroid taper. Follow-up MRI 3 months later showed a resolution of meningeal enhancement and parenchymal FLAIR hyperintensities (figure 1C, D). This improvement of the patient’s symptoms, serum blood tests and MRI results, further support our diagnosis of RM.
DISCUSSION Neurological complications of RA are uncommon. They include atlantoaxial subluxation causing spinal cord compression, central nervous system vasculitis and RM.1–3 We present a case of a 60-year-old Caucasian woman with longstanding seropositive RA with an acute psychiatric presentation that evolved into encephalopathy and seizures, with biopsy-proven granulomatous meningitis and strongly positive RA serology, most consistent with a diagnosis of RM. RM is a rare complication of RA, and usually occurs in longstanding RA.1 4 5 However, it can be an early6 or even the presenting feature.2 7 There may be dissociation between the peripheral disease activity and the RM,3 5 as in the present case. Confusion and disorientation are common:3 6 7 in one review of 19 cases, 47% patients presented with altered mental status.3 Seizures are reported in up to 21% of cases.3 5 Pachymeningeal involvement Lu L, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208745
can cause headaches1 3 6 and cranial neuropathies.7 Gait imbalance, mental status change and depression are more commonly seen in leptomeningitis.8 Focal deficits may occur,6 7 such as hemiplaegia, and optic and vestibulocochlear cranial neuropathies.3 4 Serum RF and anti-CCP are usually positive.2 3 5–7 CSF findings may be normal,5 7 show leucocytosis, elevated protein or hypoglycorrhachia.1 3 4 6 MRI of the brain may show pachy and leptomeningeal contrast enhancement and parenchymal FLAIR hyperintensity,1 2 4 5 7 but can be normal at initial presentation.6 In contrast to the typical appearance of chronic granulomatous meningeal infections such as TB and sarcoidosis, this abnormal signal is often seen over the brain convexity rather than the skull base.6 RM is difficult to diagnose and was historically often established at autopsy.1 3 Recent literature reports, however, have suggested that MRI scan and meningeal biopsy together help to establish the diagnosis.3–7 Pathological features include chronic inflammation of the meninges,4 5 7 often with a perivascular component and vasculitis;4 5 there may be necrotising granulomas with a giant cell reaction.4 6 Our patient showed strongly positive RA serology, convexal pachymeningeal enhancement on MRI and histopathological features of meningeal lymphocytic infiltration with granulomas. To date, no definitive treatment regimen has been established. There are case reports of complete remission5 or significant clinical improvements following treatment with high-dose steroids,1 4 6 7 sometimes in combination with cyclophosphamide.2 3 6 Other immunosuppressive agents such as azathioprine and methotrexate have also been reported as efficacious.6 7 Very slow tapering of steroids is generally recommended, sometimes in combination with steroid-sparing agents.3 4 6
CONCLUSIONS We present a case of RM, an extremely rare neurological complication of long standing RA. The diagnosis was based on a 3
Rare disease combination of clinical, radiological and pathological features. Clinical and radiological improvement was noted after highdose intravenous corticosteroid treatment. Clinical and pathological features of this rare condition are reviewed.
intellectual content. BC was involved in the analysis or interpretation of the data; drafting or revising the manuscript for intellectual content. PN was involved in the design and conceptualisation of the study; analysis or interpretation of the data; drafting or revising the manuscript for intellectual content. RP was involved in the acquisition, analysis and interpretation of imaging. PN and LL are responsible for the overall content as guarantors. PN identified and managed this case. Competing interests None declared.
Learning points
Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
▸ Rheumatoid meningitis is an extremely rare neurological complication of long-standing rheumatoid arthritis. ▸ The diagnosis of rheumatoid meningitis is based on a combination of clinical, radiological and pathological features. ▸ In general, if rheumatoid meningitis is suspected, high-dose steroids should be started as the initial management.
REFERENCES 1 2 3 4
Acknowledgements The authors acknowledge the assistance of Rafeeque Bhadelia, MD, Clinical Director in Neuroradiology, Associate Professor of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical, in interpreting the MRI findings. Contributors LL was involved in the design and conceptualisation of the study; analysis or interpretation of the data; drafting or revising the manuscript for
5 6 7 8
Kato T, Hoshi K, Sekijima Y, et al. Rheumatoid meningitis: an autopsy report and review of the literature. Clin Rheumatol 2003;22:475–80. Jones SE, Belsley NA, McLoud TC, et al. Rheumatoid meningitis: radiologic and pathologic correlation. AJR Am J Roentgenol 2006;186:1181–3. Bathon JM, Moreland LW, DiBartolomeo AG. Inflammatory central nervous system involvement in rheumatoid arthritis. Semin Arthritis Rheum 1989;18:258–66. Matsushima M, Yaguchi H, Niino M, et al. MRI and pathological findings of rheumatoid meningitis. J Clin Neurosci 2010;17:129–32. Krysl D, Zamecnik J, Senolt L, et al. Chronic repetitive nonprogressive epilepsia partialis continua due to rheumatoid meningitis. Seizure 2013;22:80–2. Duray MC, Marchand E, Gohy S, et al. Granulomatous meningitis due to rheumatoid arthritis. Acta Neurol Belg 2012;112:193–7. Starosta MA, Brandwein SR. Clinical manifestations and treatment of rheumatoid pachymeningitis. Neurology 2007;68:1079–80. Servioli MJ, Chugh C, Lee JM, et al. Rheumatoid meningitis. Front Neurol 2011;2:84.
Copyright 2015 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact [email protected] Visit casereports.bmj.com for more articles like this and to become a Fellow
4
Lu L, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208745
CASE REPORT
Rheumatoid meningitis: a rare complication of rheumatoid arthritis Lin Lu,1,2 Bart Chwalisz,3 Rolf Pfannl,4 Pushpa Narayanaswami3 1
School of Medicine, Imperial College London, London, Greater London, UK 2 William Harvey Hospital, Ashford, Kent, UK 3 Department of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA 4 Department of Pathology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA Correspondence to Dr Lin Lu, [email protected] Accepted 8 June 2015
SUMMARY We present a case of a 60-year-old Caucasian woman with a 23-year history of rheumatoid arthritis, who presented with a 2-week history of headache and cognitive/behavioural changes. On the basis of clinical features, radiology, laboratory data and meningeal biopsy, a diagnosis of rheumatoid meningitis was performed. High-dose intravenous methylprednisolone was used as initial treatment followed by oral prednisone. The patient’s symptoms improved and repeat MRI scans confirmed resolution of the meningeal lesions. The clinical diagnosis of rheumatoid meningitis is difficult, but it must be considered in patients with longstanding rheumatoid arthritis presenting with neurological symptoms. Glucocorticoids or other immunomodulatory therapy are the mainstay of treatment.
affect, pressured speech, flight of ideas, paranoia, disorganised thoughts, inattention, perseveration and poor short-term memory without focal sensory or motor deficits. Rheumatology review detected no acute joint inflammations, no rheumatoid nodules and no extra-articular manifestations of RA. There were no features of destructive arthritis on the X-rays of the hands. An X-ray of the right foot showed narrowed joint spaces between the first interphalangeal and fifth metatarsophalangeal joints, and mild joint subluxation at the third proximal interphalangeal joint without clear features of erosions. The X-ray of the left foot demonstrated narrowed third and fifth metatarsophalangeal joint spaces with erosive changes. These findings were consistent with inflammatory arthropathy.
INVESTIGATIONS BACKGROUND Rheumatoid meningitis (RM) is a rare manifestation of rheumatoid arthritis (RA). The non-specific clinical presentations of RM make its diagnosis difficult, and diagnosis is based on a combination of clinical, radiological and histopathological features. Prompt treatment is critical due to the high mortality rate of untreated RM. No standardised treatment regimen has been established but steroids and steroid-sparing immunosuppressive agents have both been used.
CASE PRESENTATION
To cite: Lu L, Chwalisz B, Pfannl R, et al. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2014208745
A 60-year-old Caucasian woman with a 23-year history of seropositive RA, on auranofin and prednisone, was admitted to an outside hospital for acute-onset frontal headache, photophobia and chills 6 days following a tooth extraction. Head CT at the time of presentation showed only microvascular disease. She had insomnia and multiple ‘panic attacks’ during her first admission. Symptoms resolved with tramadol and lorazepam. She was diagnosed with panic disorder and was discharged home 5 days later. Over the following 2 weeks, she developed symptoms of mania and delirium, with impaired shortterm memory and visual hallucinations, and was admitted to our hospital. Aside from the medical history of RA resistant to treatment with diseasemodifying antirheumatic drugs, she also had a history of positive PPD ( purified protein derivative) (tuberculosis/TB skin test). On examination, the patient was dishevelled and agitated; there was no fever or meningismus. Neurological examination demonstrated labile
Routine blood tests revealed an elevated white cell count (WCC) 18.6×109/L (neutrophils 66.5%), minimally raised C reactive protein (CRP) 7 mg/L (normal 0–5 mg/L) and erythrocyte sedimentation rate (ESR) was mildly elevated at 31 (normal 0–20 mm/h). Rheumatoid factor (RF) titre was >1:160 and cyclic citrullinated peptide antibody (anti-CCP) was strongly positive; other autoimmune work up was negative (antinuclear antibody, antidouble-stranded DNA, anti-Smith, antiribonucleoprotein, anti-Ro/La, thyroid peroxidase antibodies and paraneoplastic panel including antivoltage-gated potassium channel antibody). Quantiferon Gold test for TB was positive. Blood and urine bacterial cultures, serum and urine toxicology screens, and HIV and syphilis testing were negative. Cerebrospinal fluid (CSF) revealed: two WCCs (lymphocytes), three red blood cells, normal glucose (58 mg/dL) and normal protein (26 mg/dL); CSF Cryptococcus antigen, rapid plasma reagin, bacterial and fungal cultures, herpes simplex PCR and arbovirus panel were negative. MRI of the brain with gadolinium contrast revealed pachymeningeal and leptomeningeal enhancement along the left frontal and temporal lobes, with an area of adjacent parenchymal FLAIR (fluid attenuation inversion recovery) signal abnormality (figure 1A, B). EEG showed generalised slowing, most prominent over the left frontal area. CT of the torso did not reveal any systemic abnormality. Bone marrow immunophenotyping showed a non-specific T-cell-dominant lymphoid profile without clonal proliferation.
DIFFERENTIAL DIAGNOSIS The initial diagnosis was mania secondary to an organic aetiology, with speculation of possible
Lu L, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208745
1
Rare disease
Figure 1 Brain MRI with gadolinium. Axial and coronal T-1 postgadolinium brain MRI 3 weeks after symptom onset revealing abnormal pachymeningeal and sulcal enhancement along the left frontal and parietal lobes (arrows, A and B). There is resolution of the enhancement after 8 weeks of treatment with corticosteroids (arrows, C and D). Evidence of craniotomy for the brain biopsy is noted in D. infectious causes such as brain abscess, given the recent tooth extraction history; RM was considered a clinical diagnosis of exclusion. Treatment was initiated with empirical antibiotics and antiviral agents (vancomycin, ceftriaxone, metronidazole and acyclovir). Haloperidol and valproic acid were used for the behavioural symptoms, without much improvement. The patient developed partial complex seizures during her stay, despite adequate levels of valproic acid; they were controlled with the addition of phenytoin. Given the normal blood results, negative cultures/viral studies, lack of response to antibiotics and no evidence for systemic malignancy, infectious and neoplastic causes of meningitis were considered unlikely. This lack of an infectious cause of aetiology was further demonstrated by the normal CSF cell count and protein level. A left frontal meningeal biopsy was performed. On inspection, the dura was thickened, yellow and covered with friable granular tissue; the brain itself appeared intact. Histopathology revealed diffuse infiltration by lymphocytes, 2
histiocytes, plasma cells and multinucleated giant cells (figure 2). There were numerous granulomas with focal central necrosis. Fungal, treponemal and acid-fast bacilli stains were negative. The histopathological findings were felt to be consistent with rheumatoid or infectious pachymeningitis. Bacterial, fungal and acid-fast cultures were negative. TB-specific and general mycobacterial tissue PCR studies were negative, making tuberculous pachymeningitis unlikely. Therefore a diagnosis of granulomatous meningitis secondary to the RA was performed.
TREATMENT We treated this patient with intravenous pulse steroids (methylprednisolone 1000 mg daily for 5 days), followed by prednisone 60 mg tapered over several months.
OUTCOME AND FOLLOW-UP The patient had near-complete improvement in her symptoms after completing high-dose corticosteroids, with minimal residual Lu L, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208745
Rare disease
Figure 2 Histopathology (H&E stain) of the meningeal biopsy. Granulomatous meningitis with diffuse, deep infiltration of the dura by inflammatory cells (A, magnification ×40); higher power view (B, magnification ×100) showing lymphocytes, plasma cells and scattered histiocytic granulomas with multinucleated giant cells. Some granulomas reveal central necrosis (C, ×100). Multinucleated giant cells are clearly seen (D, ×200). memory impairment. Repeat blood tests showed that CRP had gone up further to 9.7 mg/L, but decreased to a normal level of 3.6 mg/L within a week of methylprednisolone administration, and had remained in the normal range since. ESR had also increased further to 56 mm/h during the patient’s hospital admission, but following the initiation of methylprednisolone it reduced to 35 mm/h and later to 0 mm/h 6 weeks post-steroid use, and subsequently remained normal. The elevated WCC at presentation was thought to be caused by the patient’s chronic steroid use before her hospital admission; the WCC increased further to 25×109/L after highdose steroids and has subsequently remained high normal/mildly elevated, ranging between 8.1 and 17.8×109/L. This is likely due to the very slow, extended steroid taper. Follow-up MRI 3 months later showed a resolution of meningeal enhancement and parenchymal FLAIR hyperintensities (figure 1C, D). This improvement of the patient’s symptoms, serum blood tests and MRI results, further support our diagnosis of RM.
DISCUSSION Neurological complications of RA are uncommon. They include atlantoaxial subluxation causing spinal cord compression, central nervous system vasculitis and RM.1–3 We present a case of a 60-year-old Caucasian woman with longstanding seropositive RA with an acute psychiatric presentation that evolved into encephalopathy and seizures, with biopsy-proven granulomatous meningitis and strongly positive RA serology, most consistent with a diagnosis of RM. RM is a rare complication of RA, and usually occurs in longstanding RA.1 4 5 However, it can be an early6 or even the presenting feature.2 7 There may be dissociation between the peripheral disease activity and the RM,3 5 as in the present case. Confusion and disorientation are common:3 6 7 in one review of 19 cases, 47% patients presented with altered mental status.3 Seizures are reported in up to 21% of cases.3 5 Pachymeningeal involvement Lu L, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208745
can cause headaches1 3 6 and cranial neuropathies.7 Gait imbalance, mental status change and depression are more commonly seen in leptomeningitis.8 Focal deficits may occur,6 7 such as hemiplaegia, and optic and vestibulocochlear cranial neuropathies.3 4 Serum RF and anti-CCP are usually positive.2 3 5–7 CSF findings may be normal,5 7 show leucocytosis, elevated protein or hypoglycorrhachia.1 3 4 6 MRI of the brain may show pachy and leptomeningeal contrast enhancement and parenchymal FLAIR hyperintensity,1 2 4 5 7 but can be normal at initial presentation.6 In contrast to the typical appearance of chronic granulomatous meningeal infections such as TB and sarcoidosis, this abnormal signal is often seen over the brain convexity rather than the skull base.6 RM is difficult to diagnose and was historically often established at autopsy.1 3 Recent literature reports, however, have suggested that MRI scan and meningeal biopsy together help to establish the diagnosis.3–7 Pathological features include chronic inflammation of the meninges,4 5 7 often with a perivascular component and vasculitis;4 5 there may be necrotising granulomas with a giant cell reaction.4 6 Our patient showed strongly positive RA serology, convexal pachymeningeal enhancement on MRI and histopathological features of meningeal lymphocytic infiltration with granulomas. To date, no definitive treatment regimen has been established. There are case reports of complete remission5 or significant clinical improvements following treatment with high-dose steroids,1 4 6 7 sometimes in combination with cyclophosphamide.2 3 6 Other immunosuppressive agents such as azathioprine and methotrexate have also been reported as efficacious.6 7 Very slow tapering of steroids is generally recommended, sometimes in combination with steroid-sparing agents.3 4 6
CONCLUSIONS We present a case of RM, an extremely rare neurological complication of long standing RA. The diagnosis was based on a 3
Rare disease combination of clinical, radiological and pathological features. Clinical and radiological improvement was noted after highdose intravenous corticosteroid treatment. Clinical and pathological features of this rare condition are reviewed.
intellectual content. BC was involved in the analysis or interpretation of the data; drafting or revising the manuscript for intellectual content. PN was involved in the design and conceptualisation of the study; analysis or interpretation of the data; drafting or revising the manuscript for intellectual content. RP was involved in the acquisition, analysis and interpretation of imaging. PN and LL are responsible for the overall content as guarantors. PN identified and managed this case. Competing interests None declared.
Learning points
Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
▸ Rheumatoid meningitis is an extremely rare neurological complication of long-standing rheumatoid arthritis. ▸ The diagnosis of rheumatoid meningitis is based on a combination of clinical, radiological and pathological features. ▸ In general, if rheumatoid meningitis is suspected, high-dose steroids should be started as the initial management.
REFERENCES 1 2 3 4
Acknowledgements The authors acknowledge the assistance of Rafeeque Bhadelia, MD, Clinical Director in Neuroradiology, Associate Professor of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical, in interpreting the MRI findings. Contributors LL was involved in the design and conceptualisation of the study; analysis or interpretation of the data; drafting or revising the manuscript for
5 6 7 8
Kato T, Hoshi K, Sekijima Y, et al. Rheumatoid meningitis: an autopsy report and review of the literature. Clin Rheumatol 2003;22:475–80. Jones SE, Belsley NA, McLoud TC, et al. Rheumatoid meningitis: radiologic and pathologic correlation. AJR Am J Roentgenol 2006;186:1181–3. Bathon JM, Moreland LW, DiBartolomeo AG. Inflammatory central nervous system involvement in rheumatoid arthritis. Semin Arthritis Rheum 1989;18:258–66. Matsushima M, Yaguchi H, Niino M, et al. MRI and pathological findings of rheumatoid meningitis. J Clin Neurosci 2010;17:129–32. Krysl D, Zamecnik J, Senolt L, et al. Chronic repetitive nonprogressive epilepsia partialis continua due to rheumatoid meningitis. Seizure 2013;22:80–2. Duray MC, Marchand E, Gohy S, et al. Granulomatous meningitis due to rheumatoid arthritis. Acta Neurol Belg 2012;112:193–7. Starosta MA, Brandwein SR. Clinical manifestations and treatment of rheumatoid pachymeningitis. Neurology 2007;68:1079–80. Servioli MJ, Chugh C, Lee JM, et al. Rheumatoid meningitis. Front Neurol 2011;2:84.
Copyright 2015 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact [email protected] Visit casereports.bmj.com for more articles like this and to become a Fellow
4
Lu L, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208745
