Current Neurology and Neuroscience Reports

, Volume 9, Issue 5, pp 359–367 | Cite as

Immunologically mediated dementias

  • Michael H. RosenbloomEmail author
  • Sallie Smith
  • Gulden Akdal
  • Michael D. Geschwind


Although most dementias are due to neurodegenerative or vascular disease, it is important to diagnose immunologically mediated dementias quickly because they can be both rapidly progressive and readily treatable. They usually affect function of limbic and cortical structures, but subcortical involvement can also occur. Because of the variety of symptoms and the rapid course, these dementias present a particular challenge to the clinician and may require evaluation and intervention in the inpatient setting. Diagnostic workup typically reveals evidence of an autoimmune process and, in some cases, cancer. In contrast to the neurodegenerative processes, many of the immunologically mediated dementias respond to immunomodulatory therapy.


Dementia Celiac Disease Paraneoplastic Syndrome Limbic Encephalitis Gluten Sensitivity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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References and Recommended Reading

  1. 1.
    Vernino S, Geschwind MD, Boeve B: Autoimmune encephalopathies. The Neurologist 2007, 13:140–147.PubMedCrossRefGoogle Scholar
  2. 2.
    Pittock SJ, Kryzer TJ, Lennon VA: Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol 2004, 56:715–719.PubMedCrossRefGoogle Scholar
  3. 3.
    Dalmau J, Rosenfeld MR: Paraneoplastic syndromes of the CNS. Lancet Neurol 2008, 7:327–340.PubMedCrossRefGoogle Scholar
  4. 4.
    Bataller L, Kleopa KA, Wu GF, et al.: Autoimmune limbic encephalitis in 39 patients: immunophenotypes and outcomes. J Neurol Neurosurg Psychiatry 2007, 78:381–385.PubMedCrossRefGoogle Scholar
  5. 5.
    Samarasekera SR, Vincent A, Welch JL, et al.: Course and outcome of acute limbic encephalitis with negative voltage-gated potassium channel antibodies. J Neurol Neurosurg Psychiatry 2007, 78:391–394.PubMedCrossRefGoogle Scholar
  6. 6.
    Vincent A, Buckley C, Schott JM, et al.: Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 2004, 127(Pt 3):701–712.PubMedGoogle Scholar
  7. 7.
    Geschwind MD, Tan KM, Lennon VA, et al.: Voltage-gated potassium channel autoimmunity mimicking Creutzfeldt-Jakob disease. Arch Neurol 2008, 65:1341–1346.PubMedCrossRefGoogle Scholar
  8. 8.
    Tan KM, Lennon VA, Klein CJ, et al.: Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology 2008, 70:1883–1890.PubMedCrossRefGoogle Scholar
  9. 9.
    Graus F, Dalmau J: Paraneoplastic neurological syndromes: diagnosis and treatment. Curr Opin Neurol 2007, 20:732–737.PubMedGoogle Scholar
  10. 10.
    Bataller L, Wade DF, Graus F, et al.: Antibodies to Zic4 in paraneoplastic neurologic disorders and small-cell lung cancer. Neurology 2004, 62:778–782.PubMedGoogle Scholar
  11. 11.
    Muehlschlegel S, Okun MS, Foote KD, et al.: Paraneoplastic chorea with leukoencephalopathy presenting with obsessive-compulsive and behavioral disorder. Mov Disord 2005, 20:1523–1527.PubMedCrossRefGoogle Scholar
  12. 12.
    Dalmau J, Graus F, Villarejo V, et al.: Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004, 127(Pt 8):1831–1844.PubMedCrossRefGoogle Scholar
  13. 13.
    Castle J, Sakonju A, Dalmau J, Newman-Toker DE: Anti-Ma2-associated encephalitis with normal FDG-PET: a case of pseudo-Whipple’s disease. Nat Clin Pract Neurol 2006, 2:566–572; quiz 573.PubMedCrossRefGoogle Scholar
  14. 14.
    Dalmau J, Gleichman AJ, Hughes EG, et al.: Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008, 7:1091–1098.PubMedCrossRefGoogle Scholar
  15. 15.
    Lai M, Hughes EG, Peng X, et al.: AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009, 65:424–434.PubMedCrossRefGoogle Scholar
  16. 16.
    Pittock SJ, Lucchinetti CF, Lennon VA: Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments. Ann Neurol 2003, 53:580–587.PubMedCrossRefGoogle Scholar
  17. 17.
    Schott JM: Another case of voltage-gated potassium channel antibody-related encephalopathy? Eur Neurol 2006, 55:110.PubMedCrossRefGoogle Scholar
  18. 18.
    McKeon A, Marnane M, O’Connell M, et al.: Potassium channel antibody associated encephalopathy presenting with a frontotemporal dementia like syndrome. Arch Neurol 2007, 64:1528–1530.PubMedCrossRefGoogle Scholar
  19. 19.
    Tuzun E, Dalmau J: Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist 2007, 13:261–271.PubMedCrossRefGoogle Scholar
  20. 20.
    Fatourechi V: Hashimoto’s encephalopathy: myth or reality? An endocrinologist’s perspective. Best Pract Res Clin Endocrinol Metab 2005, 19:53–66.PubMedCrossRefGoogle Scholar
  21. 21.
    Chong JY, Rowland LP: What’s in a NAIM? Hashimoto encephalopathy, steroid-responsive encephalopathy associated with autoimmune thyroiditis, or nonvasculitic autoimmune meningoencephalitis? Arch Neurol 2006, 63:175–176.PubMedCrossRefGoogle Scholar
  22. 22.
    Chong JY, Rowland LP, Utiger RD: Hashimoto encephalopathy: syndrome or myth? Arch Neurol 2003, 60:164–71.PubMedCrossRefGoogle Scholar
  23. 23.
    Castillo P, Woodruff B, Caselli R, et al.: Steroid-responsive encephalopathy associated with autoimmune thyroiditis. Arch Neurol 2006, 63:197–202.PubMedCrossRefGoogle Scholar
  24. 24.
    Kothbauer-Margreiter I, Sturzenegger M, Komor J, et al.: Encephalopathy associated with Hashimoto thyroiditis: diagnosis and treatment. J Neurol 1996, 243:585–593.PubMedCrossRefGoogle Scholar
  25. 25.
    Chaudhuri A, Behan PO: The clinical spectrum, diagnosis, pathogenesis and treatment of Hashimoto’s encephalopathy (recurrent acute disseminated encephalomyelitis). Curr Med Chem 2003, 10:1945–1953.PubMedCrossRefGoogle Scholar
  26. 26.
    Hollowell JG, Staehling NW, Flanders WD, et al.: Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002, 87:489–499.PubMedCrossRefGoogle Scholar
  27. 27.
    Poser S, Mollenhauer B, Kraubeta A, et al.: How to improve the clinical diagnosis of Creutzfeldt-Jakob disease. Brain 1999, 122(Pt 12):2345–2351.PubMedCrossRefGoogle Scholar
  28. 28.
    Chang CC, Eggers SD, Johnson JK, et al.: Anti-GAD antibody cerebellar ataxia mimicking Creutzfeldt-Jakob disease. Clin Neurol Neurosurg 2007, 109:54–57.PubMedCrossRefGoogle Scholar
  29. 29.
    Espay AJ, Chen R: Rigidity and spasms from autoimmune encephalomyelopathies: stiff-person syndrome. Muscle Nerve 2006, 34:677–690.PubMedCrossRefGoogle Scholar
  30. 30.
    Barker RA, Revesz T, Thom M, et al.: Review of 23 patients affected by the stiff man syndrome: clinical subdivision into stiff trunk (man) syndrome, stiff limb syndrome, and progressive encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry 1998, 65:633–640.PubMedCrossRefGoogle Scholar
  31. 31.
    Bushara KO: Neurologic presentation of celiac disease. Gastroenterology 2005, 128(4 Suppl 1):S92–S97.PubMedCrossRefGoogle Scholar
  32. 32.
    Hu WT, Murray JA, Greenaway MC, et al.: Cognitive impairment and celiac disease. Arch Neurol 2006, 63:1440–1446.PubMedCrossRefGoogle Scholar
  33. 33.
    Hadjivassiliou M, Grunewald RA, Davies-Jones GA: Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry 2002, 72:560–563.PubMedCrossRefGoogle Scholar
  34. 34.
    Ventura A, Neri E, Ughi C, et al.: Gluten-dependent diabetes-related and thyroid-related autoantibodies in patients with celiac disease. J Pediatr 2000, 137:263–265.PubMedCrossRefGoogle Scholar
  35. 35.
    Alaedini A, Green PH: Narrative review: celiac disease: understanding a complex autoimmune disorder. Ann Intern Med 2005, 142:289–298.PubMedGoogle Scholar
  36. 36.
    Green PH, Cellier C: Celiac disease. N Engl J Med 2007, 357:1731–1743.PubMedCrossRefGoogle Scholar
  37. 37.
    Boscolo S, Sarich A, Lorenzon A, et al.: Gluten ataxia: passive transfer in a mouse model. Ann N Y Acad Sci 2007, 1107:319–328.PubMedCrossRefGoogle Scholar
  38. 38.
    Alaedini A, Okamoto H, Briani C, et al.: Immune crossreactivity in celiac disease: anti-gliadin antibodies bind to neuronal synapsin I. J Immunol 2007, 178:6590–6595.PubMedGoogle Scholar
  39. 39.
    Hadjivassiliou M, Sanders DS, Woodroofe N, et al.: Gluten ataxia. Cerebellum 2008, 7:494–498.PubMedCrossRefGoogle Scholar
  40. 40.
    Hadjivassiliou M, Grunewald R, Sharrack B, et al.: Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain 2003, 126(Pt 3):685–691.PubMedCrossRefGoogle Scholar
  41. 41.
    Rosenbaum RB, Campbell SM, Rosenbaum JT: Clinical Neurology of Rheumatic Diseases. Boston: Butterworth-Heinemann; 1996.Google Scholar
  42. 42.
    Chin RL, Latov N: Central nervous system manifestations of rheumatologic diseases. Curr Opin Rheumatol 2005, 17:91–99.PubMedGoogle Scholar
  43. 43.
    Josephs KA, Rubino FA, Dickson DW: Nonvasculitic autoimmune inflammatory meningoencephalitis. Neuropathology 2004, 24:149–152.PubMedCrossRefGoogle Scholar
  44. 44.
    Delalande S, de Seze J, Fauchais AL, et al.: Neurologic manifestations in primary Sjogren syndrome: a study of 82 patients. Medicine (Baltimore) 2004, 83:280–291.CrossRefGoogle Scholar
  45. 45.
    Jennekens FG, Kater L: The central nervous system in systemic lupus erythematosus. Part 2. Pathogenetic mechanisms of clinical syndromes: a literature investigation. Rheumatology (Oxford) 2002, 41:619–630.CrossRefGoogle Scholar
  46. 46.
    Moritani T, Hiwatashi A, Shrier DA, et al.: CNS vasculitis and vasculopathy: efficacy and usefulness of diffusionweighted echoplanar MR imaging. Clin Imaging 2004, 28:261–270.PubMedCrossRefGoogle Scholar
  47. 47.
    Levine SR, Brey RL, Tilley BC, et al.: Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA 2004, 291:576–584.PubMedCrossRefGoogle Scholar
  48. 48.
    Lury KM, Smith JK, Matheus MG, Castillo M: Neurosarcoidosis3-review of imaging findings. Semin Roentgenol 2004, 39:495–504.PubMedCrossRefGoogle Scholar
  49. 49.
    Younger DS, Hays AP, Brust JC, Rowland LP: Granulomatous angiitis of the brain. An inflammatory reaction of diverse etiology. Arch Neurol 1988, 45:514–518.PubMedGoogle Scholar
  50. 50.
    Schielke E, Nolte C, Muller W, Bruck W: Sarcoidosis presenting as rapidly progressive dementia: clinical and neuropathological evaluation. J Neurol 2001, 248:522–524.PubMedCrossRefGoogle Scholar
  51. 51.
    Behcet H: Über die rezidivierende aphtÖse durch ein virus verursachte geschwüre am auge und an den genitalien. Dermatol Wochenschr 1937, 105:1152–1157.Google Scholar
  52. 52.
    Akman-Demir G, Serdaroglu P, Tasci B: Clinical patterns of neurological involvement in Behcet’s disease: evaluation of 200 patients. The Neuro-Behcet Study Group. Brain 1999, 122(Pt 11):2171–2182.PubMedCrossRefGoogle Scholar
  53. 53.
    Siva A, Kantarci OH, Saip S, et al.: Behcet’s disease: diagnostic and prognostic aspects of neurological involvement. J Neurol 2001, 248:95–103.PubMedCrossRefGoogle Scholar
  54. 54.
    Oktem-Tanor O, Baykan-Kurt B, Gurvit IH, et al.: Neuropsychological follow-up of 12 patients with neuro-Behcet disease. J Neurol 1999, 246:113–119.PubMedCrossRefGoogle Scholar
  55. 55.
    Yazici H, Yurdakul S, Hamuryudan V: Behcet disease. Curr Opin Rheumatol 2001, 13:18–22.PubMedCrossRefGoogle Scholar
  56. 56.
    Berlit P: Primary angiitis of the CNS — an enigma that needs world-wide efforts to be solved. Eur J Neurol 2009, 16:10–11.PubMedCrossRefGoogle Scholar
  57. 57.
    Iannuzzi MC, Rybicki BA, Teirstein AS: Sarcoidosis. N Engl J Med 2007, 357:2153–2165.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group, LLC 2009

Authors and Affiliations

  • Michael H. Rosenbloom
    • 1
    Email author
  • Sallie Smith
  • Gulden Akdal
  • Michael D. Geschwind
  1. 1.UCSF Memory and Aging CenterSan FranciscoUSA

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