Clinical Rheumatology

, Volume 30, Issue 4, pp 485–490

Clinical manifestations of neurological involvement in primary Sjögren’s syndrome

  • Takahisa Gono
  • Yasushi Kawaguchi
  • Yasuhiro Katsumata
  • Kae Takagi
  • Akiko Tochimoto
  • Sayumi Baba
  • Yuko Okamoto
  • Yuko Ota
  • Hisashi Yamanaka
Original Article

Abstract

The aim of this study was to evaluate neurological manifestations of primary Sjögren’s syndrome (pSS) and investigate the etiology and pathogenesis of peripheral and central nervous complications in pSS. Thirty-two patients with pSS were enrolled in the present study, 20 of whom had neurological involvement plus sicca symptoms. The clinical features were evaluated by neurological examinations including nerve conduction study, magnetic resonance imaging, cerebrospinal fluid, and electroencephalogram. The frequency of fever was significantly higher (P = 0.006) in pSS with neurological involvement than in pSS without neurological involvement. There was no statistical significance in other factors between the two groups. Peripheral nervous system (PNS), central nervous system (CNS), and both PNS and CNS involvements were revealed in 14, 3, and 3 patients, respectively. Optic neuritis and trigeminal neuralgia were revealed frequently in cranial neuropathy. Anti-aquaporin 4 antibody was detected in one patient with optic neuritis. Of the nine patients with polyneuropathy, eight patients presented pure sensory neuropathy including small fiber neuropathy (SFN). pSS with SFN appeared to have no clinically abnormal features, including muscle weakness and decreasing deep tendon reflex. Skin biopsy revealed epidermal nerve fiber degenerated in one pSS patient with pure sensory neuropathy who was diagnosed as having SFN. Our observations suggest that a number of mechanisms can be attributed to neurological involvements in pSS rather than just the mechanisms previously described (i.e., vasculitis and ganglioneuronitis). Presumably, specific autoantibodies may directly induce injury of the nervous system.

Keywords

Aquaporin 4 Sjögren’s syndrome Small fiber neuropathy 

References

  1. 1.
    Alexander E, Provost T, Stevens M, Alexander G (1982) Neurologic complications of primary Sjögren’s syndrome. Medicine (Baltimore) 61(4):247–257Google Scholar
  2. 2.
    Griffin J, Cornblath D, Alexander E, Campbell J, Low P, Bird S et al (1990) Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjögren’s syndrome. Ann Neurol 27(3):304–315PubMedCrossRefGoogle Scholar
  3. 3.
    Mellgren S, Conn D, Stevens J, Dyck P (1989) Peripheral neuropathy in primary Sjögren’s syndrome. Neurology 39(3):390–394PubMedGoogle Scholar
  4. 4.
    Hebbar M, Hebbar-Savean K, Hachulla E, Brouillard M, Hatron P, Devulder B (1995) Participation of cryoglobulinaemia in the severe peripheral neuropathies of primary Sjögren’s syndrome. Ann Med Interne (Paris) 146(4):235–238Google Scholar
  5. 5.
    Alexander E, Ranzenbach M, Kumar A, Kozachuk W, Rosenbaum A, Patronas N et al (1994) Anti-Ro(SS-A) autoantibodies in central nervous system disease associated with Sjögren’s syndrome (CNS-SS): clinical, neuroimaging, and angiographic correlates. Neurology 44(5):899–908PubMedGoogle Scholar
  6. 6.
    Lecky B, Hughes R, Murray N (1987) Trigeminal sensory neuropathy. A study of 22 cases. Brain 110(Pt 6):1463–1485PubMedCrossRefGoogle Scholar
  7. 7.
    Satake M, Yoshimura T, Iwaki T, Yamada T, Kobayashi T (1995) Anti-dorsal root ganglion neuron antibody in a case of dorsal root ganglionitis associated with Sjögren’s syndrome. J Neurol Sci 132(2):122–125PubMedCrossRefGoogle Scholar
  8. 8.
    Mori K, Iijima M, Koike H, Hattori N, Tanaka F, Watanabe H et al (2005) The wide spectrum of clinical manifestations in Sjögren’s syndrome-associated neuropathy. Brain 128(Pt 11):2518–2534PubMedCrossRefGoogle Scholar
  9. 9.
    Hoitsma E, Reulen J, de Baets M, Drent M, Spaans F, Faber C (2004) Small fiber neuropathy: a common and important clinical disorder. J Neurol Sci 227(1):119–130PubMedCrossRefGoogle Scholar
  10. 10.
    Al-Shekhlee A, Chelimsky T, Preston D (2002) Review: small-fiber neuropathy. Neurologist 8(4):237–253PubMedCrossRefGoogle Scholar
  11. 11.
    Chai J, Herrmann D, Stanton M, Barbano R, Logigian E (2005) Painful small-fiber neuropathy in Sjogren syndrome. Neurology 65(6):925–927PubMedCrossRefGoogle Scholar
  12. 12.
    Wakasugi D, Kato T, Gono T, Ito E, Nodera H, Kawaguchi Y et al (2009) Extreme efficacy of intravenous immunoglobulin therapy for severe burning pain in a patient with small fiber neuropathy associated with primary Sjögren’s syndrome. Mod Rheumatol 19:437–440PubMedCrossRefGoogle Scholar
  13. 13.
    Alexander E, Malinow K, Lejewski J, Jerdan M, Provost T, Alexander G (1986) Primary Sjögren's syndrome with central nervous system disease mimicking multiple sclerosis. Ann Intern Med 104(3):323–330PubMedGoogle Scholar
  14. 14.
    Takahashi T, Fujihara K, Nakashima I, Misu T, Miyazawa I, Nakamura M et al (2007) Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 130(Pt 5):1235–1243PubMedCrossRefGoogle Scholar
  15. 15.
    Wingerchuk D, Hogancamp W, O'Brien P, Weinshenker B (1999) The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 53(5):1107–1114PubMedGoogle Scholar
  16. 16.
    Wingerchuk D, Lennon V, Lucchinetti C, Pittock S, Weinshenker B (2007) The spectrum of neuromyelitis optica. Lancet Neurol 6(9):805–815PubMedCrossRefGoogle Scholar
  17. 17.
    Vitali C, Bombardieri S, Jonsson R, Moutsopoulos H, Alexander E, Carsons S et al (2002) Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American–European Consensus Group. Ann Rheum Dis 61(6):554–558PubMedCrossRefGoogle Scholar
  18. 18.
    McArthur J, Stocks E, Hauer P, Cornblath D, Griffin J (1998) Epidermal nerve fiber density: normative reference range and diagnostic efficiency. Arch Neurol 55(12):1513–1520PubMedCrossRefGoogle Scholar
  19. 19.
    Delalande S, de Seze J, Fauchais A, Hachulla E, Stojkovic T, Ferriby D et al (2004) Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients. Medicine (Baltimore) 83(5):280–291CrossRefGoogle Scholar
  20. 20.
    Gøransson L, Brun J, Harboe E, Mellgren S, Omdal R (2006) Intraepidermal nerve fiber densities in chronic inflammatory autoimmune diseases. Arch Neurol 63(10):1410–1413PubMedCrossRefGoogle Scholar
  21. 21.
    Lopate G, Pestronk A, Al-Lozi M, Lynch T, Florence J, Miller T et al (2006) Peripheral neuropathy in an outpatient cohort of patients with Sjögren’s syndrome. Muscle Nerve 33(5):672–676PubMedCrossRefGoogle Scholar
  22. 22.
    Moll J, Markusse H, Pijnenburg J, Vecht C, Henzen-Logmans S (1993) Antineuronal antibodies in patients with neurologic complications of primary Sjögren’s syndrome. Neurology 43(12):2574–2581PubMedGoogle Scholar
  23. 23.
    Waterman S, Gordon T, Rischmueller M (2000) Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjögren’s syndrome. Arthritis Rheum 43(7):1647–1654PubMedCrossRefGoogle Scholar
  24. 24.
    Smith A, Jackson M, Wang F, Cavill D, Rischmueller M, Gordon T (2005) Neutralization of muscarinic receptor autoantibodies by intravenous immunoglobulin in Sjögren syndrome. Hum Immunol 66(4):411–416PubMedCrossRefGoogle Scholar
  25. 25.
    Orman B, Sterin-Borda L, De Couto Pita A, Reina S, Borda E (2007) Anti-brain cholinergic auto antibodies from primary Sjögren syndrome sera modify simultaneously cerebral nitric oxide and prostaglandin biosynthesis. Int Immunopharmacol 7(12):1535–1543PubMedCrossRefGoogle Scholar
  26. 26.
    Ishida K, Uchihara T, Mizusawa H (2007) Recurrent aseptic meningitis: a new CSF complication of Sjogren’s syndrome. J Neurol 254(6):806–807PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2010

Authors and Affiliations

  • Takahisa Gono
    • 1
  • Yasushi Kawaguchi
    • 1
  • Yasuhiro Katsumata
    • 1
  • Kae Takagi
    • 1
  • Akiko Tochimoto
    • 1
  • Sayumi Baba
    • 1
  • Yuko Okamoto
    • 1
  • Yuko Ota
    • 1
  • Hisashi Yamanaka
    • 1
  1. 1.Institute of RheumatologyTokyo Women’s Medical UniversityShinjuku-KuTokyoJapan

Personalised recommendations