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Neuropathology of the Brainstem and Spinal Cord in End Stage Rheumatoid Arthritis: Implications for Treatment

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Neuropathology of the Brainstem and Spinal Cord in End Stage Rheumatoid Arthritis: Implications for Treatment Annals of the Rheumatic Diseases 1993; 52: 629-637 629 EXTENDED REPORTS Ann Rheum Dis: first published as 10.1136/ard.52.9.629 on 1 September 1993. Downloaded from Neuropathology of the brainstem and spinal cord in end stage rheumatoid arthritis: implications for treatment Fraser C Henderson, Jennian F Geddes, H Alan Crockard Abstract Methods Objective-To study the detailed histo- This study includes nine patients with sero- pathological changes in the brainstem and positive rheumatoid arthritis (eight women, spinal cord in nine patients with severe one man) from our ongoing prospective study, end stage rheumatoid arthritis, all with who underwent necropsy at the National clinical myelopathy and craniocervical Hospitals for Neurology and Neurosurgery compression. between 1987 and 1991. All patients were Methods-At necropsy the sites of bony evaluated by rheumatologists, a neurosurgeon pathology were related exactly to cord (HAC), two neuroradiologists, a physio- segments and histological changes, and therapist, and a research nurse. The clinical correlated with clinical and radiological assessment included a full neurological exam- findings. ination and a detailed questionnaire about Results-Cranial nerve and brainstem neurological symptoms. In addition, all pathology was rare. In addition to the patients were graded according to Ranawat obvious craniocervical compression, there et al'9 and Steinbrocker et al.20 The radiological were widespread subaxial changes in assessment included plain lateral films of the the spinal cord. Pathology was localised cervical spine and high definition computed primarily to the dorsal white matter and myelotomography with multiplanar refor- there was no evidence of vasculitis or matting.2' All operations were carried out by or ischaemic changes. under the direction of the same surgeon http://ard.bmj.com/ Conclusions-Myelopathy in rheumatoid (HAC). Necropsies were performed by or arthritis is probably caused by the effects under the supervision of the same neuro- of compression, stretch, and movement, pathologist (JFG). The necropsy technique not ischaemia. The additional subaxial used to remove the foramen magnum and compression may be an important com- cervical spine with the cord and medulla intact ponent in the clinical picture, and may has been described previously.22 explain why craniocervical decompression Multiple transverse blocks of the cord on September 24, 2021 by guest. Protected copyright. alone may not alleviate neurological signs. were taken, and sections stained with haema- Department of toxylin and eosin, luxol fast blue, Woelche, Neurosurgery, (Ann Rheum Dis 1993; 52: 629-637) Heidenhain, and modified Bielchowsky stains. National Naval Reticulin, Nissl, van Gieson, periodic acid- Medical Center, Bethesda, Schiff, and glial fibrillary acidic protein (Dako; MD 20814-5011, USA Rheumatoid arthritis is a systemic disease 1:400) stains were performed on selected F C Henderson affecting the cervical spine in 16-88% of blocks. Department of patients. 1-6 Progressive subluxation is com- Morbid Anatomy, mon,7-9 associated with increasing compression London Hospital Medical College, of the spinal cord and brain stem,5 1'15 and Pre-operative results Turner Street, may cause clinical myelopathy and even CLINICAL FINDINGS London El 1BB, sudden death.3 1617 Despite these clinical The table gives a summary of the principal United Kingdom J F Geddes effects, the pathophysiology and histopath- clinical details. of cord and brain stem to Department of ology injury due this The nine patients presented in this study Surgical Neurology, type of compression are poorly understood, were all white with longstanding seropositive The National Hospital and there are only two studies available in rheumatoid arthritis, aged 47-72 years for Neurology and which changes in the cord are described in any Neurosurgery, (average age 60 years, median age 64 years). Queen Square, detail.4 '8 As part of our wider study of cervical The only man in the study was the youngest London WClN 3BG, myelopathy in over 250 patients with patient. United Kingdom rheumatoid arthritis we performed a detailed All patients had been treated with steroids H A Crockard histopathological study of the spinal cord during the course of the disease, three with Correspondence to: Dr Crockard. and brain stem in nine patients, and compared gold and one with the addition of azathioprine. Accepted for publication the findings with clinical and radiological One other patient had azathioprine without 20 May 1993 features. gold. 630 Henderson, Geddes, Crockard Six of the nine patients presented with OPERATIVE FINDINGS AND COMPLICATIONS rapid neurological deterioration over three to All patients were referred for surgery because Ann Rheum Dis: first published as 10.1136/ard.52.9.629 on 1 September 1993. Downloaded from 32 weeks (average 11 weeks, median 12 of craniocervical junction compression or weeks). Patients 1, 6, and 9 had longstanding instability, or both, and, according to criteria myelopathy. outlined elsewhere,24 had transoral odon- Symptoms on presentation included neck toidectomy and decompression of the dura. pain (8/9), occipital neuralgia (8/9), hand Under the same anaesthesia a posterior numbness (7/9), weakness-usually arms occipitocervical stabilisation with a Ransford weaker than legs-(8/9), incontinence or loop and sublaminar wire fixation was carried urinary retention (4/9), dysphagia (3/9), and out. One patient (patient 5) was so ill because dyspnoea (2/9). of respiratory insufficiency that an operation Cranial nerve examination was normal in was never considered. None of the patients in all patients. A comeal ulcer was found in this study required only posterior stabilisation patient 5, but the trigeminal nerve function was without anterior decompression. Thus our normal. patients had the most severe atlantoaxial Somatosensory evoked potentials and motor compression. evoked potentials were attempted in six In three patients there were problems related patients and results obtained in four. Sleep to the passage of sublaminar wires. Two were studies of respiratory function were obtained weaker after the operation (patients 1 and 4), in three. These are the subject of another a third patient (patient 8) improved initially, study. but was readmitted six weeks later as a quadriplegic; radiographs revealed 'cut out' of the sublaminar wire at several levels and a RADIOLOGICAL FINDINGS severe subaxial cord compression at C5/6. The atlantodental interval varied from 1 to Other causes of death included haemorrhage 11 mm (average 4*7 mm, median 3 mm). There (patients 2 and 7), abscess (patient 6), was, however, marked vertical subluxation pneumomediastinitis (patient 3), and myo- of the axis in all nine patients, measuring cardial infarction (patient 9). 9-26 mm using the technique described by Redlung-Johnell and Pettersson.23 The tip of the odontoid process impinged on the upper GROSS PATHOLOGICAL FINDINGS medulla in patients 1, 8, and 9. Prominent The vertebral artery was patent in all backward tilting of the dens was present in specimens. In seven of the eight patients in patients 2 and 5 with compression of the whom an operation was performed, the medulla and upper cord at the level of C1. odontoid process and variable amounts of C2 Patient 6 had medullospinal compression only had been resected. In five of the nine patients during flexion (fig 1). The remaining patients the upper cervical cord was compressed and the dens at the flattened by the residual body of C2, and the showed cord compression by http://ard.bmj.com/ C 1 level. Major posterior compression from anteroposterior diameter of the upper two the neural arch of C 1 was apparent only in cervical segments was correspondingly much patient 7. reduced. In patient 1 the arch of C 1 was Subaxial bony changes were present in 8/9 assimilated to the occiput. In patient 7 the patients. Only patient 6 had a normal subaxial foramen magnum diameter was reduced. In spine (see table). three patients there was a markedly reduced on September 24, 2021 by guest. Protected copyright. Figure I Coronal and sagittal reformatting through the craniocervicaljunction in patient 6 after myelotomography. The broken line indicates the plane ofcoronal reformat on the sagitally reformatted image. (A) The odontoid process and lateral masses ofthe atlas and axis are eroded. (B) The brainstem is angulated and compressed by the subluxed axis. There is also mild neuraxial deformity caused by subluxation ofthe axis on the body ofC3. (C) The neuraxis is compressed on the right by granulation tissue. (D) The neuraxis has 'telescoped' through the ring of Cl. The posterior ring ofthe atlas is tilted upward, and the anterior arch tilted downward causing a 'pseudo-reduction' ofthe atlantodental interval. Neuropathology of the brainstem and spinal cord in end stage RA 631 Summary ofclinical and radiologicalfindings Patient Age Duration of Findings before Ranawatl mm Vertical Subaxial changes Operative Findings after Timefrom Ann Rheum Dis: first published as 10.1136/ard.52.9.629 on 1 September 1993. Downloaded from No (years)! disease (years)! operation American axial findings operation operation sex drugs received Rheumatism subluxation! to death Association ADI (mm)/ (days) grades CSA cord (mm2) * 1 47/M 25/gold Normoreflexia, IIIb/4 23/11/60 Fibrous, Fibrous pannus, Neurologically 56 quadriparesis, ankylosis C2-C6 C1 fracture, unchanged, normal sensation anterior Cl tetraplegic on day 2 fused to clivus 2
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