Advertisement

Acta Neuropathologica

, Volume 112, Issue 2, pp 217–225 | Cite as

Relapsing polychondritis with features of dementia with Lewy bodies

  • Elizabeth Head
  • Arnold Starr
  • Ronald C.  Kim
  • Anna Parachikova
  • Genaro E.  Lopez
  • Malcolm Dick
  • David H. Cribbs
Case Report

Abstract

We describe a 72-year old man with clinical features suggestive of dementia with Lewy bodies (DLB) who proved neuropathologically to have degeneration induced by relapsing polychondritis (RP), an autoimmune inflammatory disorder of cartilaginous tissues. There was lymphocytic infiltration of the leptomeninges, perivascular cuffing, reactive astrocytosis, and activation of microglia in multiple brain areas all consistent with an immunologically mediated process. There was widespread neuronal loss within the hippocampus, entorhinal cortex, and amygdala as well as diffuse myelin pallor of cortical pathways. Elevated levels of complement proteins and endothelial markers of inflammation were observed, which are similar to previous reports in DLB. This study demonstrates that qualitatively similar inflammation-associated neurodegeneration is present in widespread regions of the brain in a RP case presenting clinically as DLB.

Keywords

Complement Hippocampal cell loss Neuroinflammation White matter degeneration 

Notes

Acknowledgments

Funding supported by ADRC P50 AG16573, P50 AG000658, NIA-AG-20241 and NINDS-NS50895 (DHC). We would also like to extend our gratitude to the patient and his family for their assistance in the study.

References

  1. 1.
    Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WST, Hampel H, Hull M, Landreth G, Lue LF, Mrak R, Mackenzie IR, McGeer PL, O’Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T (2000) Inflammation and Alzheimer’s disease: neuroinflammation working group. Neurobiol Aging 21:383–421PubMedCrossRefGoogle Scholar
  2. 2.
    Babcock AA, Kuziel WA, Rivest S, Owens T (2003) Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J Neurosci 23:7922–7930PubMedGoogle Scholar
  3. 3.
    Belfor N, Amici S, Boxer AL, Kramer JH, Gorno-Tempini ML, Rosen HJ, Miller BL (2006) Clinical and neuropsychological features of corticobasal degeneration. Mech Ageing Dev 127:203–207PubMedCrossRefGoogle Scholar
  4. 4.
    Berg AM, Kasznica J, Hopkins P, Simms RW (1996) Relapsing polychondritis and aseptic meningitis. J Rheumatol 23:567–569PubMedGoogle Scholar
  5. 5.
    Bornke C, Heye N, Buttner T (1999) Rapidly progressive dementia. Lancet 353:1150PubMedCrossRefGoogle Scholar
  6. 6.
    Brod S, Booss J (1988) Idiopathic CSF pleocytosis in relapsing polychondritis. Neurology 38:322–323PubMedGoogle Scholar
  7. 7.
    Calabrese P (2006) Neuropsychology of multiple sclerosis—an overview. J Neurol 253(Suppl I):10–15CrossRefGoogle Scholar
  8. 8.
    Chakravarty S, Herkenham M (2005) Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. J Neurosci 25:1788–1796PubMedCrossRefGoogle Scholar
  9. 9.
    Christine CW, Aminoff MJ (2004) Clinical differentiation of parkinsonian syndromes: prognostic and therapeutic relevance. Am J Med 117:412–419PubMedCrossRefGoogle Scholar
  10. 10.
    The National Institute on Aging and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease (1997) Consensus recommendations for the post mortem diagnosis of Alzheimer’s disease. Neurobiol Aging 18:1–2Google Scholar
  11. 11.
    Dreher A, Aigner J, Fuchshuber S, Kastenbauer E (2000) Relapsing polychondritis: a course over 20 years with cerebral involvement. Arch Otolaryngol Head Neck Surg 126:1495–1498PubMedGoogle Scholar
  12. 12.
    Foidart JM, Abe S, Martin GR, Zizic TM, Barnett EV, Lawley TJ, Katz SI (1978) Antibodies to type II collagen in relapsing polychondritis. N Engl J Med 299:1203–1207PubMedCrossRefGoogle Scholar
  13. 13.
    Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state: a practical method for grading the cognitive status of patients for the clinician. J Psychiatry Res 12:189–198CrossRefGoogle Scholar
  14. 14.
    Fujiki F, Tsuboi Y, Hashimoto K, Nakajima M, Yamada T (2004) Non-herpetic limbic encephalitis associated with relapsing polychondritis. J Neurol Neurosurg Psychiatr 75:1646–1647PubMedCrossRefGoogle Scholar
  15. 15.
    Gambetti P, Kong Q, Zou W, Parchi P, Chen SG (2003) Sporadic and familial CJD: classification and characterisation. Br Med Bull 66:213–239PubMedCrossRefGoogle Scholar
  16. 16.
    Gergely P Jr, Poor G (2004) Relapsing polychondritis. Best Pract Res Clin Rheumatol 18:723–738PubMedCrossRefGoogle Scholar
  17. 17.
    Hanslik T, Wechsler B, Piette JC, Vidailhet M, Robin PM, Godeau P (1994) Central nervous system involvement in relapsing polychondritis. Clin Exp Rheumatol 12:539–541PubMedGoogle Scholar
  18. 18.
    Harkness KA, Coles A, Pohl U, Xuereb JH, Baron JC, Lennox GG (2004) Rapidly reversible dementia in cerebral amyloid inflammatory vasculopathy. Eur J Neurol 11:59–62PubMedCrossRefGoogle Scholar
  19. 19.
    Head E, Azizeh BY, Lott IT, Tenner AJ, Cotman CW, Cribbs DH (2001) Complement association with neurons and beta-amyloid deposition in the brains of aged individuals with Down syndrome. Neurobiol Dis 8:252–265PubMedCrossRefGoogle Scholar
  20. 20.
    Hickey WF (2001) Basic principles of immunological surveillance of the normal central nervous system. Glia 36:118–124PubMedCrossRefGoogle Scholar
  21. 21.
    Imamura K, Hishikawa N, Ono K, Suzuki H, Sawada M, Nagatsu T, Yoshida M, Hashizume Y (2005) Cytokine production of activated microglia and decrease in neurotrophic factors of neurons in the hippocampus of Lewy body disease brains. Acta Neuropathol (Berl) 109:141–150CrossRefGoogle Scholar
  22. 22.
    Iseki E, Marui W, Akiyama H, Ueda K, Kosaka K (2000) Degeneration process of Lewy bodies in the brains of patients with dementia with Lewy bodies using alpha-synuclein-immunohistochemistry. Neurosci Lett 286:69–73PubMedCrossRefGoogle Scholar
  23. 23.
    Jaksch-Wartenhorst R (1923) Polychondropathia. Wein Arch Inn Med 6:93–100Google Scholar
  24. 24.
    Kent PD, Michet CJ Jr, Luthra HS (2004) Relapsing polychondritis. Curr Opin Rheumatol 16:56–61PubMedCrossRefGoogle Scholar
  25. 25.
    Konsman JP, Parnet P, Dantzer R (2002) Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci 25:154–159PubMedCrossRefGoogle Scholar
  26. 26.
    Kothare SV, Chu CC, VanLandingham K, Richards KC, Hosford DA, Radtke RA (1998) Migratory leptomeningeal inflammation with relapsing polychondritis. Neurology 51:614–617PubMedGoogle Scholar
  27. 27.
    Mackenzie IR (2000) Activated microglia in dementia with Lewy bodies. Neurology 55:132–134PubMedGoogle Scholar
  28. 28.
    Mackenzie IR (2001) Cortical inflammation in dementia with Lewy bodies. Arch Neurol 58:519–520PubMedCrossRefGoogle Scholar
  29. 29.
    Maltete D, Guyant-Marechal L, Mihout B, Hannequin D (2006) Movement disorders and Creutzfeldt–Jakob disease: a review. Parkinsonism Relat Disord 12:65–71PubMedCrossRefGoogle Scholar
  30. 30.
    Massry GG, Chung SM, Selhorst JB (1995) Optic neuropathy, headache, and diplopia with MRI suggestive of cerebral arteritis in relapsing polychondritis. J Neuroophthalmol 15:171–175PubMedGoogle Scholar
  31. 31.
    McAdam LP, O’Hanlan MA, Bluestone R, Pearson CM (1976) Relapsing polychondritis: prospective study of 23 patients and a review of the literature. Medicine (Baltimore) 55:193–215CrossRefGoogle Scholar
  32. 32.
    McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, Dickson D, Dubois B, Duda JE, Feldman H, Gauthier S, Halliday G, Lawlor B, Lippa C, Lopez OL, Carlos Machado J, O’Brien J, Playfer J, Reid W (2004) Dementia with Lewy bodies. Lancet Neurol 3:19–28PubMedCrossRefGoogle Scholar
  33. 33.
    Nadeau SE (2002) Neurologic manifestations of connective tissue disease. Neurol Clin 20:151–178, viGoogle Scholar
  34. 34.
    Newman TA, Woolley ST, Hughes PM, Sibson NR, Anthony DC, Perry VH (2001) T-cell- and macrophage-mediated axon damage in the absence of a CNS-specific immune response: involvement of metalloproteinases. Brain 124:2203–2214PubMedCrossRefGoogle Scholar
  35. 35.
    Nguyen MD, Julien JP, Rivest S (2002) Innate immunity: the missing link in neuroprotection and neurodegeneration? Nat Rev Neurosci 3:216–227PubMedCrossRefGoogle Scholar
  36. 36.
    Ohta Y, Nagano I, Niiya D, Fujioka H, Kishimoto T, Shoji M, Abe K (2004) Nonparaneoplastic limbic encephalitis with relapsing polychondritis. J Neurol Sci 220:85–88PubMedCrossRefGoogle Scholar
  37. 37.
    Panisset M, Roudier M, Saxton J, Boller F (1994) Severe impairment battery. A neuropsychological test for severely demented patients. Arch Neurol 51:41–45PubMedGoogle Scholar
  38. 38.
    Perry VH, Newman TA, Cunningham C (2003) The impact of systemic infection on the progression of neurodegenerative disease. Nat Rev Neurosci 4:103–112PubMedCrossRefGoogle Scholar
  39. 39.
    Ragnaud JM, Tahbaz A, Morlat P, Sire S, Gin H, Aubertin J (1996) Recurrent aseptic purulent meningitis in a patient with relapsing polychondritis. Clin Infect Dis 22:374–375PubMedGoogle Scholar
  40. 40.
    Rampello L, Butta V, Raffaele R, Vecchio I, Battaglia G, Cormaci G, Alvano A (2005) Progressive supranuclear palsy: a systematic review. Neurobiol Dis 20:179–186PubMedCrossRefGoogle Scholar
  41. 41.
    Rivest S (2003) Molecular insights on the cerebral innate immune system. Brain Behav Immun 17:13–19PubMedCrossRefGoogle Scholar
  42. 42.
    Rozemuller AJ, Eikelenboom P, Theeuwes JW, Jansen Steur EN, de Vos RA (2000) Activated microglial cells and complement factors are unrelated to cortical Lewy bodies. Acta Neuropathol (Berl) 100:701–708CrossRefGoogle Scholar
  43. 43.
    Shepherd CE, Thiel E, McCann H, Harding AJ, Halliday GM (2000) Cortical inflammation in Alzheimer disease but not dementia with Lewy bodies. Arch Neurol 57:817–822PubMedCrossRefGoogle Scholar
  44. 44.
    Spiegel J, Hellwig D, Becker G, Muller M (2004) Progressive dementia caused by Hashimoto’s encephalopathy—report of two cases. Eur J Neurol 11:711–713PubMedCrossRefGoogle Scholar
  45. 45.
    Stewart SS, Ashizawa T, Dudley AW Jr, Goldberg JW, Lidsky MD (1988) Cerebral vasculitis in relapsing polychondritis. Neurology 38:150–152PubMedGoogle Scholar
  46. 46.
    Sundaram MB, Rajput AH (1983) Nervous system complications of relapsing polychondritis. Neurology 33:513–515PubMedGoogle Scholar
  47. 47.
    Thibeault I, Laflamme N, Rivest S (2001) Regulation of the gene encoding the monocyte chemoattractant protein 1 (MCP-1) in the mouse and rat brain in response to circulating LPS and proinflammatory cytokines. J Comp Neurol 434:461–477PubMedCrossRefGoogle Scholar
  48. 48.
    Togo T, Iseki E, Marui W, Akiyama H, Ueda K, Kosaka K (2001) Glial involvement in the degeneration process of Lewy body-bearing neurons and the degradation process of Lewy bodies in brains of dementia with Lewy bodies. J Neurol Sci 184:71–75PubMedCrossRefGoogle Scholar
  49. 49.
    Trentham DE, Le CH (1998) Relapsing polychondritis. Ann Intern Med 129:114–122PubMedGoogle Scholar
  50. 50.
    Wasserfallen JB, Schaller MD (1992) Unusual rhombencephalitis in relapsing polychondritis. Ann Rheum Dis 51:1184PubMedCrossRefGoogle Scholar
  51. 51.
    Yamada T, McGeer PL, McGeer EG (1992) Lewy bodies in Parkinson’s disease are recognized by antibodies to complement proteins. Acta Neuropathol (Berl) 84:100–104CrossRefGoogle Scholar
  52. 52.
    Zeuner M, Straub RH, Rauh G, Albert ED, Scholmerich J, Lang B (1997) Relapsing polychondritis: clinical and immunogenetic analysis of 62 patients. J Rheumatol 24:96–101PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Elizabeth Head
    • 1
    • 2
  • Arnold Starr
    • 1
    • 2
  • Ronald C.  Kim
    • 1
  • Anna Parachikova
    • 1
  • Genaro E.  Lopez
    • 1
  • Malcolm Dick
    • 1
  • David H. Cribbs
    • 1
    • 2
  1. 1.Institute for Brain Aging and DementiaUniversity of CaliforniaIrvineUSA
  2. 2.Department of Neurology, College of MedicineUniversity of CaliforniaIrvineUSA

Personalised recommendations