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The patient was a woman whose illness had begun at the age of 40 with Raynaud’s phenomenon, progressing to distal necrosis and ulceration of fingertips, with sclerosis of the hands, feet and face. The results of investigation were consistent with systemic sclerosis (SS). Subsequently she reported heartburn and regurgitation, and oesophageal manometry revealed a defect compatible with SS. Findings on oesophagogastroscopy and echocardiography were normal; respiratory function tests showed slight ventilatory dysfunction. At age 46 she sought advice after six months of progressive unsteadiness and ataxia. On examination her gait was broad-based and she had cephalic and intention tremors with bilateral dysmetria. Motor and sensory nerve function was normal. Tests for antinuclear, anticentromere and anti-SSA antibodies were positive; those for anti-SSB, anti-dsDNA, anti-Jo1, anti-Scl70 and anti-RNP were negative. She did not report dry eyes or dry mouth and Schirmer’s test was negative. The echocardiogram and the respiratory function tests had not changed. Cranial CT (Figure 1) revealed severe diffuse symmetrical cerebellar atrophy without evidence of demyelination or infarction; no lacunae (basal or cortical) were present and the supratentorial subarachnoid space was normal; there were no features suggestive of vascular disease and the carotid and vertebral arteries showed no calcifications. The patient did not use alcohol and did not recall any exposure to toxic substances; investigations for possible underlying occult neoplasia were negative. After methylprednisolone pulse therapy (1 g per day for three days) the cerebellar signs improved and she became able to walk without assistance, though the ataxia and unsteadiness did not resolve completely. A year later, pulmonary hypertension was diagnosed (pulmonary artery systolic pressure 58 mm Hg) with depression of right ventricular function, dilatation of the right atrium and tricuspid insufficiency. Helical thoracic CT showed no evidence of vascular thrombi or pulmonary fibrosis and the ventilation–perfusion scan did not support the diagnosis of pulmonary embolism. The pulmonary hypertension was interpreted as secondary to the pulmonary microvascular disease of systemic sclerosis. Intravenous Iloprost (a prostacyclin analogue) decreased the pulmonary systolic pressure to 41 mm Hg and she improved clinically. She was then switched to inhaled Iloprost and the improvement continued after discharge. The cerebellar ataxia was no worse than it had been a year before. A month after discharge, she was readmitted severely hypoxic with pneumonia and had an irreversible cardiorespiratory arrest.
This patient had typical systemic sclerosis with skin and oesophageal involvement and progressive pulmonary hypertension. The unusual clinical feature was the ataxia due to cerebellar atrophy. The diagnosis of systemic sclerosis was supported by the finding of anticentromere antibodies (associated with the development of non-fibrotic pulmonary hypertension in that condition3) and antinuclear antibodies (present in more than 70% of patients3,4); the anti-SSA antibodies were also consistent with the diagnosis.3,5 Progressive subacute cerebellar degeneration can be part of a paraneoplastic syndrome, but there was no evidence of neoplasia on investigation or subsequent follow-up.
In SLE, central nervous system disease is frequent whereas in systemic sclerosis it is rare6 and apparently unrelated to systemic vascular damage.7 We have found no previous reports of cerebellar atrophy associated with systemic sclerosis. The features resembled those in occasional cases of SLE, as did the response to treatment. Al Arfaj and Naddaf1 saw one patient with cerebellar ataxia in a series of 150 with SLE and this patient responded to high-dose steroids and azathioprine; Singh et al.2 detected cerebellar signs in 3 of 350 SLE patients, and these patients too improved on steroid therapy. The mechanism in some patients may be immunological. Tomita8 identified in an animal model of SLE a specific cytokine profile with enhanced gene expression of interleukin (IL)-6, interferon-gamma, IL-1β and IL-10 associated with the development of cerebellar signs. We likewise speculate that the cerebellar involvement in our patient with systemic sclerosis was a manifestation of autoimmunity.