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Transverse myelopathy is a rare complication of mixed connective tissue disease (MCTD). To date there have been relatively few reports, all in females.1-6 We describe a case of transverse myelopathy in a man with MCTD and review the previous cases, comparing them with transverse myelopathy related to systemic lupus erythematosus (SLE).
A 46 year old man with a history of a squamous cell carcinoma of his right upper lobe bronchus and a 2 year history of MCTD was admitted to hospital with a 3 month history of subacute progressive lower limb weakness, sensory loss, and sphincter disturbance. He had been diagnosed with MCTD on the basis of Raynaud's phenomenon, polyarthralgia, synovitis, acrosclerosis, raised muscle enzymes, biopsy established myositis, dysphagia for solids, positive test for antinuclear factor (ANF) (speck1ed 1/2560), negative DNA binding, and high titre antiribonuclear protein (anti-RNP). His bronchial carcinoma had been treated surgically with a right pneumonectomy and radiotherapy to the bronchial stump at a low dose of 3000 cgrad over 10 days. No lymph node involvement was identified either at operation or on CT. He had recently been prescribed a reducing course of prednisolone for active myositis. There was no history of recent infections.
On examination he was systemically well. There was no clinical evidence of tumour recurrence. He had an asymmetric spastic paraparesis (power of 4–4+ MRC grading) with a sensory level at D10. The remainder of the neurological examination was normal. Brain and spinal cord MRI with gadolinium enhancement showed mild atrophy of the cord at D9/D10 but was otherwise normal. Routine haematology (full blood count, vitamin B12, and folate), inflammatory markers, and biochemistry were normal. ANF remained at high titre with anti-RNP antibody positivity. All other autoimmune markers and serum angiotensin converting enzyme were normal. A thrombophilia screen (protein C, protein S, and antithrombin III, lupus anticoagulant, and anticardiolipin) was unremarkable. Complement, creatinine phosphokinase, and immunoglobulins were normal, and a venereal disease research laboratory test was negative. Examination of CSF excluded infection and standard indices were normal. Oligoclonal bands were negative and visual evoked potentials were normal.
He received high dose steroid therapy (1g/day intravenous prednisolone for 3 days followed by an oral reducing dose) and was started on 125 mg azathioprine. There was no further deterioration in his condition and at 6 year follow up his neurological condition remains stable. No recurrence of carcinoma was detected over the same time period and we think that a paraneoplastic cause can be excluded. Similarly, radiation myelopathy is unlikely, as no vertebral abnormalities were seen on MRI and the patient had only a small radiation dose to a localised field.
Transverse myelopathy is a rare complication of MCTD and has not been previously reported in a male. Postulated mechanisms include vasculitis of small arachnoid arteries of the cord and arterial thrombosis causing microinfarction of the spinal cord because of necrotising vasculitis or the presence of a circulating antiphospholipid antibody. The patient presented after an interval of several months from onset of symptoms. It is possible that the initial pathology was related to a vasculitis that had resolved by the time of presentation. Magnetic resonance findings in transverse myelopathy depend on the timing of the examination and the stage of disease. In this case the delay to presentation may explain the fact that MRI demonstrated atrophy of the cord only.
The table shows features of this patient, and of other reports of transverse myelopathy related to MCTD. Transverse myelopathy was noted to occur relatively early in the evolution of MCTD, although in no patient was it a presenting feature. By contrast, retrospective studies of patients with SLE and transverse myelopathy found that transverse myelopathy was a presenting feature in 50%.7 8 All cases of MCTD related transverse myelopathy involved the thoracic region. One patient also had a cervical myelopathy. In SLE, a retrospective analysis7 found the cervical cord to be the most commonly affected site (50%). The onset was reported as progressive in all cases with MCTD, although the duration of symptom onset was not precisely identified in every report. By contrast, however, a review of 20 cases of transverse myelopathy related to SLE,9 showed that 50% evolved over less than a day. Neurological improvement or resolution with only mild sequelae followed treatment with high dose prednisolone and azathioprine in five of the seven cases of transverse myelopathy related to MCTD. In this case and one other in which there was a delay in presentation of over 4 weeks, neurological features were stabilised but did not improve. The clinical course of transverse myelopathy related to SLE is variable, although historically prognosis is relatively poor. In one series in which 70% of patients received steroid treatment, 50% died in less than 6 weeks, 35% had permanent neurological deficits, and 15% had a near normal recovery.9 Another study8 described seven patients with transverse myelopathy and SLE. Four died and one remained wheelchair bound. In SLE, early aggressive therapy with high dose steroids and cytotoxic agents has been associated with a satisfactory outcome.7 8 10
Considering this patient together with previous reports suggests that, by contrast with SLE, transverse myelopathy is unlikely to be a presenting feature of MCTD. Onset is progressive rather than acute, and cervical areas are less often involved.Transverse myelopathy associated with MCTD would seem intrinsically to have a better prognosis, as improvement or resolution occurred in 70% of cases treated with prednisolone and azathioprine. In this and one other patient there was a delay to presentation of over 4 weeks and no neurological improvement was noted. We therefore suggest that whereas high dose prednisolone and azathioprine generally seems sufficient to treat MCTD associated transverse myelopathy, if there is a delay to presentation more aggressive immunosuppression may be appropriate.
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