Frontotemporal Lobar Degeneration from the Perspective of the New Clinical‑ Pathological Correlations

Czech version

Authors: S. Šutovský ¹; M. Králová ³; B. Kollár ¹; P. Šiarnik ¹; J. Dragašek ²; Ľ. Izáková ³; P. Turčáni ¹
Authors‘ workplace: I. neurologická klinika LF UK a UN Bratislava ¹; Psychiatrická klinika UPJŠ v Košiciach ²; Psychiatrická klinika LF UK a UN Bratislava ³
Published in: Cesk Slov Neurol N 2013; 76/109(6): 679-689
Category: Review Article

Overview

The disease currently known as Frontotemporal Lobar Degeneration (FTLD) underwent a complicated development. From its first description by Arnold Pick and Alois Alzheimer, through the first clinical and pathological criteria introduced by David Neary and David Mann to the current perception of the disease as a complex clinical and pathological entity. At present, the Frontotemporal Lobar Degeneration is understood to be a heterogeneous clinical syndrome caused by degeneration of the frontal and temporal lobes. FTLD can manifest as any of the three clinical syndromes of frontotemporal dementia (behavioural variant of frontotemporal dementia, progressive non‑fluent aphasia and semantic dementia) as well as so called overlap syndromes encompassing corticobasal dementia and progressive supranuclear palsy. FTLD represents approximately 10% of all cases of dementia but 40% of cases of early onset dementia (between the age of 45 and 65 years). Although FTLD subtypes differ in their clinical manifestation, common denominators include behavioural disturbances and impairment of fatic, gnostic and executive functions. Mnestic and visual‑ spatial functions are preserved until advanced stages of the disease. Compared to Alzheimer’s disease, the FTLD usually onsets at an earlier age and causes more devastating impairment of cognitive domains. Persons affected by FTLD become more quickly dependent on the help of other person or an institution. In our paper, we provide an overview of this complex entity, focusing mainly on frontotemporal dementia syndromes.

Key words:
frontotemporal lobar degeneration – frontotemporal dementia – progressive non-fluent aphasia – semantic dementia – tau protein – tautopathy – ubiquitin – TDP-43 protein – behavioural disturbances – speech disorder

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Sources

1. Pick A. Über die Beziehungen der senilen Hirnatrophie zur Aphasie. Prager Med Wochenschr 1882; 17 :165– 167.

2. Pick A. Senile Hirnatrophie als Grundlage von Herderscheinungen. Wien Klin Wochenschr 1901; 14: 403– 404.

3. Pick A. Zur Symptomatologie der linksseitigen Schlafenlappenatrophie. Monatschr Psychiatr Neurol 1904; 16: 378– 388.

4. Alzheimer A. Über eigenartige Krankheitsfälle des späteren Alters. Z Gesamte Neurol Psychiatr 1911; 4: 356– 385.

5. Hudson AJ. Amyotrophic lateral sclerosis and its association with dementia, parkinsonism and other neurologic disorders: a review. Brain 1981; 104(2): 217– 247.

6. Mitsuyama Y. Presenile dementia with motor neuron disease in Japan: clinical pathological review of 26 cases. J Neurol Neurosurg Psychiatr 1984; 47: 953– 959.

7. Maurita K, Kaiya H, Ikeda T, Namba M. Presenile dementia combined with amyotrophy: a review of 34 Japanese cases. Arch Gerontol Geriatr 1987; 6(3): 263– 277.

8. Neary D, Snowden JS, Mann DM, Northen B, Goulding PJ, Macdermott N. Frontal lobe dementia and motor neuron disease. J Neurol Neurosurg Psychiatr 1990; 53(1): 23– 32.

9. Neary D, Snowden JS, Mann D. Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. J Neurol Neurosurg Psychiatry 1994; 57(4): 416– 418.

10. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51(6): 1546– 1554.

11. Kipps CM, Knibb JA, Hodges JR. Clinical presentation of frontotemporal dementia In: Hodges JR (ed). Frontotemporal dementia syndromes. Cambridge: Cambridge University Press 2007: 38– 79

12. Litvan I. Cortocobasal degeneration. In: Atypical Parkinsonian Disorders – Clinical and Research Aspects. Humana Press 2005: 309– 335.

13. Litvan I. Progressive supranuclear palsy. In: Litvan I (ed). Atypical Parkinsonian Disorders – Clinical and Research Aspects. New York: Humana Press 2005: 287– 309.

14. Josephs KA, Hodges JR, Snowden JS, Mackenzie IR, Neumann M, Mann DM et al. Neuropathological background of phenotypical variability in frontotemporal dementia. Acta Neuropathol 2011; 122(2): 137– 153.

15. Snowden JS, Bathgate D, Varma A, Blackshaw A,Gibbons ZC, Neary D. Distinct behavioural profiles in frontotemporaldementia and semantic dementia. J Neurol Neurosurg Psychiatry 2001; 70(3): 323– 332.

16. Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134(Pt 9): 2456– 2477.

17. Šutovský S, Malík M, Traubner P, Turčáni P. Primárna progresívna afázia – zriedkavá alebo poddiagnistikovaná. Neurol Prax 2007; 8(3): 170– 173.

18. Rektorová I. Frontotemporální lobární degenerace – diagnóza z neuro‑psychiatrického pomezí. Neurol Prax 2006; 7(4): 208– 211.

19. Rektorová I. Neurodegenerativní demence. Cesk Slov Neurol N 2009; 72/ 105(2): 97– 109.

20. Gorno‑ Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF et al. Classification of primary progressive aphasia and its variants. Neurology 2011; 76(11): 1006– 1014.

21. Vyhnálek M, Škoda D, Varjassyová A, Hort J. Sémantická demence – důkaz mnohotvárnosti paměťových procesů. Neurol Prax 2005; 6(6): 316– 318.

22. van de Pol LA, Hensel A, van der Flier WM, Visser PJ, Pijnenburg YA, Barkhof F et al. Hippocampal atrophy on MRI in frontotemporal lobar degeneration and Alzheimer‘s disease. J Neurol Neurosurg Psychiatry 2006; 77(4): 439– 442.

23. Spillantini MG, Bird TD, Ghetti B. Frontotemporal dementia and parkinsonism linked to chromosome 17: a new group of tauopathies. Brain Pathol 1998; 8(2): 387– 402.

24. Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ et al. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the consortium for frontotemporal lobar degeneration consortium for rontotemporal lobar degeneration. Acta Neuropathol 2007; 114(1): 5– 22.

25. Mackenzie IR, Foti D, Woulfe J, Hurwitz TA. Atypical frontotemporal lobar degeneration with ubiquitin‑positive, TDP‑ 43– negative neuronal inclusions. Brain 2008; 131(Pt 5): 1282– 1293.

26. Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J et al. Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol 2009; 117(1): 15– 18.

27. Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J et al. Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol 2010; 119(1): 1– 4.

28. Hodges JR, Davies RR, Xuereb JH, Casey B, Broe M,Bak TH et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol 2004; 56(3): 399– 406.

29. Josephs KA, Petersen RC, Knopman DS, Boeve BF, Whitwell JL, Duffy JR et al. Clinicopathologic analysis of frontotemporal and corticobasal degenerations andPSP. Neurology 2006; 66(1): 41– 48.

30. Kertesz A, McMonagle P, Blair M, Davidson W,Munoz DG. The evolution and pathology of frontotemporal dementia. Brain 2005; 128(Pt 9): 1996– 2005.

31. Snowden J, Neary D, Mann D. Frontotemporal lobar degeneration: clinical and pathological relationships. Acta Neuropathol 2007; 114(1): 31– 38.

32. Grossman M. The non‑fluent/ agrammatic variant of primary progressive aphasia. Lancet Neurol 2012; 11(6): 545– 555.

33. Sanders J, Schenk VW, van Veen PF et al. A family with Pick disease. Amsterdam: Veerhandelingen de Koninklijike Nederlandese Akademie van Wetenschappen 1939.

34. Rizzu P, Van Swieten JC, Joosse M, Hasegawa M, Stevens M, Tibben A et al. High prevalence of mutations in the microtubule‑associated protein tau in a population study of frontotemporal dementia in the Netherlands. Am J Hum Genet 1999; 64(2): 414– 421.

35. Gass J, Cannon A, Mackenzie IR, Boeve B, Baker M,Adamson J et al. Mutations in progranulin are a major cause of ubiquitin‑positive frontotemporal lobar degeneration. Hum Mol Genet 2006; 15(20): 2988– 3001.

36. Sieben A, Van Langenhove T, Engelborghs S, Martin JJ, Boon P, Cras P et al. The genetics and neuropathology of frontotemporal lobar degeneration. Acta Neuropathol 2012; 124(3): 353– 372.

37. Majounie E, Renton AE, Mok K, Dopper EG, Waite A,Rollinson S et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross‑ sectional study. Lancet Neurol 2012; 11(4): 323– 330.

38. Mackenzie IR, Neumann M, Cairns NJ, Munoz DG, Isaacs AM. Novel types of frontotemporal lobar degeneration: beyond tau and TDP‑ 43. J Mol Neurosci 2011; 45(3): 402– 408.

39. Goedert M, Spillantini MG. Pathogenesis of the tauopathies. J Mol Neurosci 2011; 45(3): 425– 431.

40. Snowden JS, Thompson JC, Stopford CL, Richardson AM, Gerhard A, Neary D et al. The clinical diagnosis of early‑ onset dementias: diagnostic accuracy and clinicopathological relationships. Brain 2011; 134(Pt 9): 2478– 2492.

41. Polymenidou M, Lagier‑ Tourenne C, Hutt KR, Huelga SC, Moran J, Liang TY et al. Long pre‑mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP‑ 43. Nat Neurosci 2011; 14(4): 459– 468.

42. Lagier‑ Tourenne C, Polymenidou M, Hutt KR, Vu AQ, Baughn M, Huelga SC et al. Divergent roles of ALS‑linked proteins FUS/ TLS and TDP‑ 43 intersect in processing long pre‑mRNAs. Nat Neurosci 2012; 15(11): 1488– 1497.

43. Ressner P, Hort J, Rektorová I, Bartoš A, Rusina R, Línek V et al. Doporučené postupy pro diagnostiku Alzheimerovy nemoci a dalších onemocnění spojených s demencí. Cesk Slov Neurol N 2008; 71/ 104(4): 494– 501.

44. Hort J, Glosová L, Vyhnálek M, Bojar M, Škoda D,Hladíková M. Tau protein a beta amyloid v likvoru u Alzheimerovy choroby. Cesk Slov Neurol N 2007; 70/ 103(1): 30– 36.

45. Dubois B, Feldman HH, Jacova C, Cummings JL, Dekosky ST, Barberger‑ Gateau P et al. Revising the definition of Alzheimer‘s disease: a new lexicon. Lancet Neurol 2010; 9(11): 1118– 1127.

46. Pijnenburg YA, Schoonenboom NS, Rosso SM, Mulder C, Van Kamp GJ, Van Swieten JC et al. CSF tau and Abeta42 are not useful in the diagnosis of frontotemporal lobar degeneration. Neurology 2004; 62(9): 1649.

47. Schoonenboom NS, Reesink FE, Verwey NA, Kester MI, Teunissen CE, van de Ven PM et al. Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort. Neurology 2012; 78(1): 47– 54.

48. Sorbi S, Hort J, Erkinjuntti T, Fladby T, Gainotti G,Gurvit H et al. EFNS Scientist Panel on Dementia and Cognitive Neurology. EFNS‑ ENS Guidelines on the diagnosis and management of disorders associated with dementia. Eur J Neurol 2012; 19(9): 1159– 1179.

49. Bibl M, Mollenhauer B, Lewczuk P, Esselmann H, Wolf S, Otto M et al. Cerebrospinal fluid tau, p‑ tau 181 and amyloid‑ b38/ 40/ 42 in frontotemporal dementias and primary progressive aphasias. Dement Geriatr Cogn Disord 2011; 31(1): 37– 44.

50. Verwey NA, Kester MI, van der Flier WM, Veerhuis R,Berkhof H, Twaalfhoven H et al. Additional value of CSF amyloid‑beta 40 levels in the differentiation between FTLD and control subjects. J Alzheimers Dis 2010; 20(2): 445– 452.

51. Hu WT, Chen‑ Plotkin A, Grossman M, Arnold SE, Clark CM, Shaw LM et al. Novel CSF biomarkers for frontotemporal lobar degenerations. Neurology 2010; 75(23): 2079– 2086.

52. Freedman M. Frontotemporal dementia: recommendations for therapeutic studies, designs, and approaches. Can J Neurol Sci 2007; 34 (Suppl 1): S118– S124.

53. Seltman RE, Matthews BR. Frontotemporal lobar degeneration: epidemiology, pathology, diagnosis and management. CNS Drugs 2012; 26(10): 841– 870.

54. Lampl Y, Sadeh M, Lorberboym M. Efficacy of acetylcholinesterase inhibitors in frontotemporal dementia. Ann Pharmacother 2004; 38(11): 1967– 1968.

55. Boxer AL, Knopman DS, Kaufer DI, Grossman M, Onyike C, Graf‑ Radford N et al. Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double‑blind, placebo‑ controlled trial. Lancet Neurol 2013; 12(2): 149– 156.

56. New Drugs Online [on‑line]. Available from URL: http:/ / www.ukmi.nhs.uk/ applications/ ndo/ record_view_open.asp?newDrugID=5763.