Q J Med 2004; 97: 241-242
QJM vol. 97 no. 4 (c) Association of Physicians 2004; all rights reserved.
Correspondence |
Painful arm in syringomyelia and Fabry disease
Sir,A 28-year-old male patient with a previous diagnosis of Fabry disease presented with new-onset, severe paroxysmal shooting pain affecting his left arm. This was different from his previous experience of intermittent pain in the extremities (acroparaesthesias), which was reasonably controlled on carbamazepine therapy. The painful paroxysms were acute and unpredictable, and involved his left arm, left shoulder and left side of his chest, lasting for several minutes to hours. These were considered to be due to ‘Fabry crises’.1 On physical examination, he had diminished left arm reflexes with absent left triceps jerk, and sensory loss of pain and temperature, extending to left shoulder and trunk in a hemicape distribution. Ophthalmic examination showed vortex keratopathy but preserved corneal reflexes. He had angiokeratoma in the characteristic bathing suit distribution (Figure 1).
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MRI scans of his brain and spinal cord showed syringomyelia extending from C2 to D10 segments, associated with type 1 Chiari malformation (Figure 2a and b). There was no ischaemic brain lesion. His renal function and echocardiography were normal. He was subsequently treated with recombinant enzyme replacement therapy (ERT) with agalsidase beta 1 mg/kg every fortnight. There was a significant remission of his painful paroxysms on ERT. His syringomyelia was unchanged clinically and on serial MRI scans during two years’ of follow up.
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Fabry disease is an X-linked systemic metabolic disorder where glycosphingolipids accumulate in the vascular endothelial tissues, due to the deficiency of lysosomal enzyme alpha-galactosidase A.1 While cerebrovascular disease and progressive renal failure are considered to be the late complications of the untreated disease, pain is considered to be the most debilitating symptom in the early decades of life.2 Acroparaesthesia typically begins in childhood or adolescence, and episodic pain due to Fabry crises are common1. Pain in Fabry disease is considered to be due to the involvement of small myelinated peripheral nerve fibres and the dorsal root ganglion.3
The literature of Fabry disease mostly consists of single or small case studies, and the association of Fabry disease and syringomyelia with type I Chiari malformation has not been previously reported. It is possible that the co-occurrence of the two rare disorders is purely coincidental in the present case. Association of syringomyelia and Chiari malformation is, however, well recognized. It has been hypothesized that the enlarged perivascular (Virchow-Robin) space is the portal of entry of fluid from the spinal subarachnoid space into the spinal cord, leading to the formation of syrinx in syringomyelia associated with Chiari malformation.4 Glycolipid accumulation in Fabry disease is known to affect vascular function, but whether it might have directly contributed to the development of syrinx in this case is speculative.
At the time of presentation, the patient had frequent, painful paroxysms affecting his left arm (Fabry crises) with markedly reduced pain perception in the same region due to syringomyelia. Segmentally dissociated anaesthesia is a characteristic feature of syringomyelia, and is considered to be the result of progressive destruction of the central projections of the afferent sensory neurons by the fluid-filled cavity (syrinx) within the spinal cord. Painful crises are not known in syringomyelia. The episodic segmental pain in the left arm of our patient with sensory loss and cervical syrinx suggests that pain in Fabry crises could not have been due to the involvement of peripheral afferent sensory pathways,3 and might have a central origin. Brain pathology in Fabry disease consists of both vascular lesions and neuronal lipid accumulation.5 Clinical observation in this patient seems to suggest that a central, neurovascular mechanism may be responsible for paroxysmal pain in Fabry crises. Therapeutic experience in the present case also shows that the ERT is effective in relieving painful crises in Fabry disease.
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Department of Neurology Institute of Neurological Sciences University of Glasgow e-mail: ac54p{at}udcf.gla.ac.uk
References
1. Desnick RJ, Brady R, Barranger J, Collins AJ, Germain DP, Goldman M, et al. Fabry disease, an under-recognised multisystemic disorder: Expert recommendations for diagnosis, management and enzyme replacement therapy. Ann Intern Med 2003; 138:338–46.
2. McGovern MM. Lysosomal storage diseases. In: Fauci AS, Martin JB, Braunwald E, et al., eds. Harrison's Principles of Internal Medicine, 14th edn. New York, McGraw-Hill, 1997:2169–76.
3. Ball MJ, Dayan AD. Pathogenesis of syringomyelia. Lancet 1972; ii:799–801.
4. Kahn P. Anderson-Fabry disease: a histological study of three cases with observations on the mechanism of production of pain. J Neurol Neurosurg Psychiatry 1973; 36:1053–62.[ISI][Medline]
5. Kaye EM, Kolodny EH, Logigian EL, Ullman MD. Nervous system involvement in Fabry disease: clinicopathological and biochemical correlation. Ann Neurol 1988; 23:505–9.[CrossRef][ISI][Medline]
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