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Sjögren syndrome (SS) is a systemic autoimmune disorder predominantly affecting the exocrine glands, involving the CNS in 20%–25% of cases. Previous neuropathologic specimens in Sjögren myelopathy have suggested a vasculitic pathophysiology.
A 66-year-old woman developed sicca symptoms followed by subacutely evolving neck pain, paraparesis, and paresthesias below her neckline. She had 5 similar attacks over ensuing months, partially improved by IV methylprednisolone, but gradually became cane dependent and noted anesthesia below her chest. Her only regular medication was benazepril.
One year later, her symptoms recurred, and she presented to our institution. On examination, there was flaccid hyporeflexic upper extremity paresis with areflexic paraplegia. A T5 sensory level was noted. There was no optic disc pallor, dysmetria, or dyssynergia.
Brain MRI was unremarkable except for small vessel disease. Spinal MRI showed multiple patchily enhancing, longitudinal white matter lesions (several extending over 3 corresponding vertebral body segments) from the medullary spinal junction to the conus medullaris.
CSF showed protein 208, glucose 79, 9 erythrocytes, and 9 leukocytes, including 6 lymphocytes, 2 histiocytes, and 1 neutrophil. CSF de novo immunoglobulin G (IgG) synthesis was 45.6 (−9.9 to 3.3 mg/day) and CSF IgG index was 0.8 (0.0–0.7). Possible matching IgG bands in serum and CSF were seen. SSA, SSB, antinuclear antibodies (1:320, normal 1:40), Smith (1:50), and RNP (1:100) were positive. Serum NMO IgG antibody was negative.
A biopsy of dura, epidura, and (T8–T10) spinal cord revealed extensive demyelination without evidence of vasculitis or malignancy (figure). A minor salivary gland biopsy was consistent with SS. The patient was subsequently treated with cyclophosphamide and hydroxychloroquine for 6 months without improvement.
Our patient presented with relapsing inflammatory myelopathy initially responsive to steroid therapy. While MS or NMO were considered, we believed a diagnosis of Sjögren myelopathy was more likely due to the clearcut associated SS diagnosis (serology and biopsy proven), older patient age, and lack of NMO antibodies or historical optic neuritis. However, the possibility of a primary form of NMO in evolution, or of overlapping comorbid NMO spectrum disorder, remains possible since serum NMO antibody positivity is not invariably present in patients with clinically established NMO, and given that NMO seropositivity is less frequent in those with isolated recurrent longitudinally extensive transverse myelitis (LETM).1 CSF NMO antibody testing is occasionally diagnostic in seronegative NMO patients without optic nerve involvement, but was not obtained in our patient.2
SS is an autoimmune connective tissue disorder characterized by lymphocytic infiltration of exocrine glands and B-lymphocyte hyperactivity. CNS involvement has been estimated to affect 10%–25% of SS patients.3 Common associated neurologic manifestations of SS are sensory neuropathy and trigeminal neuropathy. Spinal cord presentations may include acute transverse myelopathy, chronic progressive myelopathy, and Brown-Sequard syndrome.3,4
Peripheral nerve biopsies in patients with SS with peripheral nervous system symptomatology have revealed vasculitis or perivascular mononuclear cell infiltration.4
The pathogenesis of CNS SS has remained unclear. CNS involvement by SS has been postulated to have a vasculitic pathophysiology similar to previously reported pathologic specimens from peripheral nerve and other organs. Previous pathology in CNS SS has shown vasculitis or a perivascular mononuclear infiltration. Microinfarcts and microhemorrhages with hypertrophic or damaged endothelial cells have also been seen.3,4
CNS involvement in SS could also arise from autoimmune demyelination. Recently published cases have linked SS to Devic neuromyelitis.5 Another case of SS revealed necrosis and demyelination of the cerebellar white matter postmortem.6
A longitudinal study suggested that anti-CNS antibodies may be an important marker for cerebral involvement in connective tissue diseases.7 Demyelination could represent one stage of pathogenesis in a vasculitic myelopathy. However, the biopsy in our patient was performed following subacute deterioration after months of illness, and no evidence of active or previous blood vessel involvement such as areas of infarctions, hemorrhage, or perivascular lymphocytic infiltrates were seen, making a vasculitic pathophysiology unlikely.
SS should be considered in the differential diagnosis of inflammatory myelopathy, especially in the presence of sicca symptoms. The intramedullary demyelination unassociated with NMO antibodies seen in our case expands the spectrum of known pathophysiology seen in CNS SS. Additional tissue from future biopsies and autopsies are needed to clarify the pathogenesis of Sjögren myelopathy and hopefully guide more specific treatments.
Disclosure: Dr. Chahin and Dr. Garwood report no disclosures. Dr. St. Louis served on a scientific advisory board for Lundbeck Inc./Ovation Pharmaceuticals, Inc.; has served as a consultant for and received speaker honoraria from GlaxoSmithKline, Ortho-McNeil-Janssen Pharmaceuticals, Inc., Shire plc, Impax Laboratories, Inc., and UCB; and has received research support from SCHWARZ PHARMA AG, Marinus Pharmaceuticals, Inc., NeuroVista Corporation, the CDC [Award 5 R49 CE721682-05 (PI)], the NIH [K12 510 17 3220 04000 11812015 (PI)], and the University of Iowa. Dr. Shivapour has served as a consultant for and received speaker honoraria from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Merck Serono. Dr. Kelkar has received speaker honorarium from Biogen Idec. Dr. Granner served as a consultant for Lundbeck Inc./Ovation Pharmaceuticals, Inc.; served on speakers’ bureaus for UCB and GlaxoSmithKline; and received research support from Marinus Pharmaceuticals, Inc. and NeuroVista Corporation.
Received October 30, 2008. Accepted in final form September 16, 2009.
Address correspondence and reprint requests to Dr. Salim Chahin, Department of Neurology, UIHC, 2RCP, 200 Hawkins Drive, Iowa City, IA 52242; ude.awoiu@nihahc-milas