1. Rheumatoid arthritis in the brain- a diagnosis of exclusion
Dr Suzanne O’Leary
SpR Neuroradiology
Frenchay Hospital
Bristol UK

2. Bristol case 59 year old female patient
Known diagnosis of Rheumatoid arthritis
RA affecting joints only. Inactive at time of this presentation
Otherwise well
No previous neurological condition

3. Presentation Severe headache that had persisted for 2 weeks
Headache had been sudden in onset and very severe.
Initially a diagnosis of SAH was considered

4. CT head
NO ICH
Bifrontal low attenuation consistent with oedema. Callosal splenium thickening.
? Intrinsic tumour
? Inflammatory process
? infection
MRI advised

5. Deterioration
Patient becoming increasingly confused and absent episodes.
Acyclovir started
ECG, CXR,FBC, MSU normal.
No evidence of infection.
ESR elevated
ANA positive
RhF positive

6. MRI
FLAIR
T1W
DWI
T2W

7. MRI- T1W + GAD

8. MRI findings
Post  contrast  images  show  leptomeningeal  enhance ment  either side  of  the  falx  in  the  anterior  interhemispheric  fissu re, with  enhancement  of  the  dura  over  the  falx  at  this  site. There  is  reactive  oedema  in  the  adjacent  anteromed ial frontal  lobes.
Appearances  are  unusual  but  clearly  demonstrate  a  meningeal process  which  may  be  inflammatory,  reactive  or  mal ignant. Is  there  any  abnormality  on  lumbar  puncture?

9. CT angiogram

10. CTA The medial frontal lobes demonstrate paucity of vessels.
The vessels that are visible are irregular in outline. 10

11. Catheter angiogram

12. Catheter angiogram findings
There  is abnormality  in  the  vasculature  supplying the  medial  frontal  lobes  bilaterally  where  there  is  slight reduction  in  vascularity  and  evidence  of  vascular irregularity  including  general  stenosis  with  pruning  and beading  in  places.  There  is  no  arteriovenous  shunting.  T here does  not  appear  to  be  involvement  of  any  of  the  more proximal  vessels.  No  other  territories  appear  to  be involved.
The  abnormal  vasculature  corresponds  to  the abnormality on the CT and MRI.   This raises  the  possibility  of  a  vasculitic  process accounting  for  the  changes  on  the  CT  and  in  the  anteri or cerebral  artery  distribution  predominantly  callosal  marginal .

13. Lumbar puncture Lymphocytosis Protein increase Glucose reduced
Gram stain, ZN stain, India ink, mycobacterium and fungal cultures were negative.
Treated with Acyclovir on admission

14. Brain biopsy- Rheumatoid meningitis and vasculitis
Fibrinoid necrosis
Surrounded by histiocytes
Dense infiltrate of plasma cells within the subarachnoid space
Vasculitis of the leptomeninges and underlying cortex
Staining for bacteria, acid-fast bacillii, fungi and spirochetes was negative.

15. Diagnosis
Definite diagnosis of Rheumatoid meningitis and vasculitis made
Patient started on steroids and immunosuppressants
Clinical improvement within days
Discharged home after 7 days.

16. Rheumatoid Arthritis
Systemic inflammatory disorder, usually affecting the joints.
Extra-articular sites affected, including skin, lungs, eyes and blood vessels.
Blood vessels are involved, it is medium and small vessels of the skin and peripheral nervous system which are more commonly affected.
There are case reports of it affecting the brain, causing a cerebral vasculitis and rarely causes meningitis or pachymeningitis.
The neurological sequelae of RA cause death in 18.6% of cases.
This is often a diagnosis of exclusion, and brain biopsy may be required.

17. Rheumatoid arthritis and the brain
Nervous system involvement with RA is uncommon.
Neurologic complications are usually due to mass effect on the spinal cord or peripheral nerves from synovitis, pannus formation or subluxation
Direct involvement of the CNS includes pachymeningitis, leptomeningitis and vasculitis.
Rarer complications include organic brain syndrome and progressive multifocal leukoencephalopathy.
CNS involvement can occur without typical extracranial patterns of RA.
Neurologic symptoms of rheumatoid meningitis include cranial nerve dysfunction, seizure, mental status change, and hemiparesis or paraparesis.
CSF analysis are usually abnormal, with an elevated protein level, occasional pleocytosis and a low glucose level.
The diagnosis is one of exclusion, and all other causes of leptomeningitis and pachymeningitis must be considered
Diagnosis is aided by a clinical diagnosis of RA, positive serologic results for rheumatoid factors, and the pathologic visualization of rheumatoid nodules.

18. Leptomeningitis/ Pachymeningitis
Lepto/Pachymeningitis contains a nonspecific infiltrate of mononuclear cells, particularly plasma cells. Less frequently seen are areas of necrosis and multinucleated giant cells. Although they may be present in 60% of cases, rheumatic nodules often do not cause symptoms. The presence of epithelioid granulomas typically in the cranial meninges or choroid plexus confirms the diagnosis of rheumatoid meningitis but is not a specific finding.
CNS symptoms can be caused by a CNS vasculitis due to a lymphoplasmacytic infiltrate in the vessel walls. This involves both parenchymal and meningeal vessels. Large vessels, such as the middle cerebral artery, are usually spared.

19. Leptomeningitis/ Pachymeningitis
Infection-TB, fungal, cysticercosis, pyogenic
Tumour- lymphoma, leukaemia, carcinomatosis, meningioma
Inflammation- sarcoid, Whipples, Behcets, Sjogrens, Wegners, Temporal arteritis, RA
Idiopathic pachymeningitis
Intracerebral hypotension. 19

20. Conclusion Rare complication of RA
Need to exclude all other causes of lepto/pachymeningitis.
Brain biopsy may be necessary
Poor prognosis- 6 months 20

21. References
1. Jones SE, Belsley NA, Mcloud TC,Mullins ME. Rheumatoid Meningitis: Radiologic and Pathologic correlation. AJR 2006;186:
2. Tan HJ,Raymond AA, Phadke PP, Rozman Z. Rheumatoid pachymeningitis. Singapore Med J 2004;45(7):337
3. Agildere AM, Tutar NU, Yucel E, Coskun M. Case report. Pachymeningitis and optic neuritis in rheumatoid arthritis: MRI findings. BR J Radiol 1999;72:404-7
4.William TC, Drew JM, Rizzo M, Ryals TJ, Sato Y, Bell WE. Evaluation of pachymeningitis by contrast-enhanced MR imaging in a patient with rheumatoid disease. AM J Neuroradiol 1990: 11: 21

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