rheumatoid meningoencephalitis ( rm ) is a rare extra - articular complication of rheumatoid arthritis ( ra ) . rm usually develops in patients with a long history of ra , regardless of disease activity of systemic arthritis . the diagnosis of rm is difficult because the etiology of meningitis varies and there are no definite criteria for the diagnosis of rm . nevertheless , early diagnosis of rm is important because immunosuppressive therapies can significantly improve patient prognosis [ 2 , 3 , 4 ] . magnetic resonance imaging ( mri ) of the brain has been reported to be helpful for the diagnosis of rm , even during early stages . because of its high specificity , the presence of anti - cyclic citrullinated peptide ( ccp ) antibody is useful for the early diagnosis of ra , as well as for the prediction of future ra development in asymptomatic individuals . this report describes the development of anti - ccp antibody - positive meningoencephalitis in a patient lacking a history of ra , suggesting that rm may have developed prior to the onset of ra in this patient . a healthy 63-year - old man was admitted to our hospital with headache , vomiting , and vertigo for several days . on admission , his body temperature was 38.5c , and he was slightly confused , but with normal orientation . he showed nuchal rigidity , but presented neither neurological deficits nor any signs of ra . laboratory examinations showed a slight elevation in erythrocyte sedimentation rate ( 18 mm / h ) and c - reactive protein concentration ( 0.4 mg / dl ) . examination of his cerebrospinal fluid ( csf ) showed mild lymphocytic pleocytosis ( 37 cells / mm ) and elevated protein concentration ( 98 mg / dl ) , but a normal glucose level . his csf was negative for pathogens , including viruses , bacteria , mycobacteria , and fungi . immunological tests , including antinuclear antibody , anti - neutrophil cytoplasmic antibodies against myeloperoxidase and protease 3 , antibodies to double - stranded dna , anti - ssa , and anti - ssb were all negative . fluid - attenuated inversion recovery ( flair ) images showed high - intensity lesions in the subarachnoid spaces ( fig . an electroencephalogram showed theta waves in the bilateral frontoparietal region without epileptic discharges . following a preliminary diagnosis of aseptic meningoencephalitis , he was started on empirical treatment with acyclovir ( 10 mg / kg / day ) . however , his high - grade fever persisted , and he became further disoriented and began behaving abnormally . mri on day 8 showed that the high - intensity lesions in the bilateral frontoparietal meninges and the subarachnoid space had worsened ( fig . the serum concentrations of both rheumatoid factor ( rf ) ( 140 iu / ml ; normal < 15 iu / ml ) and anti - ccp antibody ( 472 u / ml ; normal the csf concentration of anti - ccp antibody was 4.4 u / ml and that of interleukin-6 ( il-6 ) was 482 pg / ml ( normal < 12.1 pg / ml ) . although he did not fulfill the diagnostic criteria for ra at that time , he was diagnosed with rm based on the presence of anti - ccp antibody and mri results . he was started on intravenous high - dose methylprednisolone treatment ( 1,000 mg / day ) for 3 days . by day 12 , this treatment had resulted in drastic improvements in his symptoms and reduced his high - intensity lesions on mri . on day 13 , however , he again displayed disturbed consciousness and high - grade fever , with the level of anti - ccp antibody in csf further elevated to 26.2 u / ml . he was re - treated with intravenous methylprednisolone therapy for 3 days , followed by oral administration of 50 mg / day prednisolone , with the latter subsequently tapered . his symptoms gradually resolved along with reductions in csf concentrations of anti - ccp antibody ( 8.5 u / ml ) and il-6 ( 15.2 pg / ml ) as well as serum concentrations of rf ( 60 iu / ml ) and anti - ccp antibody ( 248 u / ml ) . two months later the patient , while continuing on 30 mg / day prednisolone , was re - admitted due to metacarpophalangeal arthritis . laboratory data demonstrated increases in white blood cell count ( 13,720/l ) , c - reactive protein ( 5.7 mg / dl ) , rf ( 568 iu / ml ) , as well as anti - ccp antibody in serum ( 877 u / ml ) and csf ( 10.7 u / ml ) . this report describes a patient with aseptic meningoencephalitis developing 2 months before the onset of ra . mri findings and the presence of anti - ccp antibody highly suggested that the meningoencephalitis was rm . pathophysiologically , rm is thought to be caused by microvasculitis associated with ra [ 6 , 7 ] . microscopic examination demonstrated rheumatoid nodules , nonspecific meningeal inflammation , and vasculitis , as well as lymphocyte and plasma cell infiltration of small vessel walls . most patients with rm have long - standing ra before the onset of rm [ 2 , 3 , 4 ] and show elevated rf in serum and csf [ 8 , 9 ] . however , there are no definitive diagnostic criteria or specific diagnostic markers for rm . although a brain biopsy is usually required to diagnose this condition , limited tissue sampling can not always show the specific pathological features of rm , such as rheumatoid nodules . our patient could not be diagnosed with rm on admission because he had no history of ra or articular manifestations . to our knowledge , there has been only one case report describing a patient with rheumatoid pachymeningitis preceding the onset of ra . that patient was a 67-year - old man who presented with acute sensorineural hearing loss . his serum was positive for high - titer rf , but negative for anti - ccp antibody . although that patient was treated with prednisolone and methotrexate , he manifested ra 3 months later without recovery of hearing loss . although both this patient and ours showed elevated serum rf and abnormal mri findings , the previous patient was negative for anti - ccp antibody , whereas ours was positive . rm may be considered in the differential diagnosis of aseptic meningitis in patients with ra and the following features : ( 1 ) high - intensity lesions are present in the subarachnoid spaces on flair or diffusion - weighted images , ( 2 ) leptomeningeal abnormalities are focal , ( 3 ) the basal cisterns are usually not affected , ( 4 ) the response to corticosteroid is rapid , and ( 5 ) serum is positive for anti - ccp antibody . the presence of anti - ccp antibody may be particularly important for the diagnosis of ra because of its high specificity ( 96% ) . anti - ccp antibody can also be useful in the diagnosis of the preclinical period of ra [ 5 , 13 ] . the presence of autoantibody prior to articular manifestations of ra may indicate that immune dysregulation occurs prior to symptom onset . the presence of anti - ccp antibody can predict the development of articular ra in patients with lung disorders , such as interstitial lung disease and certain diseases of the airways . thus , the combination of anti - ccp antibody in serum and mri findings may be useful in diagnosing rm prior to the onset of ra . in conclusion , the findings in this patient suggest that rm can develop in patients without a history of ra . the presence of anti - ccp antibody in serum , along with mri , is helpful for the diagnosis of rm .
rheumatoid meningoencephalitis ( rm ) is a rare complication of rheumatoid arthritis ( ra ) . 
 this report describes a 63-year - old man with complaints of high - grade fever , headache , and vomiting for several days before admission . 
 both his serum and cerebrospinal fluid were positive for anti - cyclic citrullinated peptide ( ccp ) antibody and rheumatoid factor , and contrast - enhanced fluid - attenuated inversion recovery magnetic resonance imaging ( mri ) showed abnormal gadolinium enhancement of the meninges and high - intensity lesions in the subarachnoid spaces . 
 the patient was diagnosed with rm despite lack of signs suggesting ra . 
 his symptoms drastically improved with intravenous infusion of high - dose methylprednisolone . 
 two months later , he developed ra . 
 the findings in this patient suggest that rm could develop prior to the onset of ra . 
 anti - ccp antibody and mri findings may be useful for the diagnosis of rm , regardless of ra history .