nach oben

Journal of Neurology

Erschienen in:

01.08.2015 | Neurological Update

Progress in Huntington’s disease: the search for markers of disease onset and progression

verfasst von: Sarah Mason, Roger A. Barker

Erschienen in: Journal of Neurology | Ausgabe 8/2015

Einloggen, um Zugang zu erhalten

Abstract

Unlike most neurodegenerative disorders, individuals at risk from Huntington’s disease can be identified prior to the onset of clinical signs of the disease by virtue of it being an autosomal dominant condition. This provides the hypothetical opportunity to delay disease onset and/or slow down the progression of the disease in the very early stages ahead of overt features of disease. To help prepare for therapeutic trials of disease-modifying compounds, extensive work has gone into (1) finding ways of better predicting the onset of disease in pre-manifest HD gene carriers (PMGC), (2) defining the extent of non-motor features of HD and (3) identifying robust and reliable tests by which to measure disease progression. In this short review, we summarise some of the major findings in this area of clinical research.

Andrich J, Schmitz T, Saft C, Postert T, Kraus P, Epplen JT, Przuntek H, Agelink MW (2002) Autonomic nervous system function in Huntington’s disease. J Neurol Neurosurg Psychiatry 72:726–731PubMedCentralCrossRefPubMed

Aylward EH, Anderson NB, Bylsma FW, Wagster MV, Barta PE, Sherr M, Feeney J, Davis A, Rosenblatt A, Pearlson GD, Ross CA (1998) Frontal lobe volume in patients with Huntington’s disease. Neurology 50:252–258CrossRefPubMed

Aylward EH, Codori AM, Barta PE, Pearlson GD, Harris GJ, Brandt J (1996) Basal ganglia volume and proximity to onset in presymptomatic Huntington disease. Arch Neurol 53:1293–1296CrossRefPubMed

Aziz NA, Anguelova GV, Marinus J, van Dijk JG, Roos RA (2010) Autonomic symptoms in patients and pre-manifest mutation carriers of Huntington’s disease. Eur J Neurol 17:1068–1074CrossRefPubMed

Begeti F, Tan AY, Cummins GA, Collins LM, Guzman NV, Mason SL, Barker RA (2013) The Addenbrooke’s Cognitive Examination-Revised accurately detects cognitive decline in Huntington’s disease. J Neurol 260:2777–2785CrossRefPubMed

Byars JA, Beglinger LJ, Moser DJ, Gonzalez-Alegre P, Nopoulos P (2012) Substance abuse may be a risk factor for earlier onset of Huntington disease. J Neurol 259:1824–1831CrossRefPubMed

Csernansky JG, Dong H, Fagan AM, Wang L, Xiong C, Holtzman DM, Morris JC (2006) Plasma cortisol and progression of dementia in subjects with Alzheimer-type dementia. Am J Psychiatry 163:2164–2169PubMedCentralCrossRefPubMed

Dumas EM, van den Bogaard SJ, Middelkoop HA, Roos RA (2013) A review of cognition in Huntington’s disease. Front Biosci (Schol Ed) 5:1–18CrossRef

Dumas EM, van den Bogaard SJ, Ruber ME, Reilman RR, Stout JC, Craufurd D, Hicks SL, Kennard C, Tabrizi SJ, van Buchem MA, van der Grond J, Roos RA (2012) Early changes in white matter pathways of the sensorimotor cortex in premanifest Huntington’s disease. Hum Brain Mapp 33:203–212CrossRefPubMed

10.

Dumas JA, Kutz AM, McDonald BC, Naylor MR, Pfaff AC, Saykin AJ, Newhouse PA (2013) Increased working memory-related brain activity in middle-aged women with cognitive complaints. Neurobiol Aging 34:1145–1147PubMedCentralCrossRefPubMed

11.

Goodman AO, Rogers L, Pilsworth S, McAllister CJ, Shneerson JM, Morton AJ, Barker RA (2011) Asymptomatic sleep abnormalities are a common early feature in patients with Huntington’s disease. Curr Neurol Neurosci Rep 11:211–217CrossRefPubMed

12.

Harris GJ, Codori AM, Lewis RF, Schmidt E, Bedi A, Brandt J (1999) Reduced basal ganglia blood flow and volume in pre-symptomatic, gene-tested persons at-risk for Huntington’s disease. Brain 122(Pt 9):1667–1678CrossRefPubMed

13.

Hart EP, Dumas EM, Reijntjes RH, van der Hiele K, van den Bogaard SJ, Middelkoop HA, Roos RA, van Dijk JG (2012) Deficient sustained attention to response task and P300 characteristics in early Huntington’s disease. J Neurol 259:1191–1198PubMedCentralCrossRefPubMed

14.

Hart EP, Dumas EM, van Zwet EW, van der Hiele K, Jurgens CK, Middelkoop HA, van Dijk JG, Roos RA (2013). Longitudinal pilot-study of Sustained attention to response task and P300 in manifest and pre-manifest Huntington’s disease. J Neuropsychol

15.

Herben-Dekker M, van Oostrom JC, Roos RA, Jurgens CK, Witjes-Ane MN, Kremer HP, Leenders KL, Spikman JM (2014) Striatal metabolism and psychomotor speed as predictors of motor onset in Huntington’s disease. J Neurol 261:1387–1397CrossRefPubMed

16.

Hocaoglu MB, Gaffan EA, Ho AK (2012) Health-related quality of life in Huntington’s disease patients: a comparison of proxy assessment and patient self-rating using the disease-specific Huntington’s disease health-related quality of life questionnaire (HDQoL). J Neurol 259:1793–1800PubMedCentralCrossRefPubMed

17.

Johnson JM, Kellogg DL Jr (2010) Local thermal control of the human cutaneous circulation. J Appl Physiol 109:1229–1238PubMedCentralCrossRefPubMed

18.

Kobal J, Melik Z, Cankar K, Bajrovic FF, Meglic B, Peterlin B, Zaletel M (2010) Autonomic dysfunction in presymptomatic and early symptomatic Huntington’s disease. Acta Neurol Scand 121:392–399CrossRefPubMed

19.

Kobal J, Melik Z, Cankar K, Strucl M (2014) Cognitive and autonomic dysfunction in presymptomatic and early Huntington’s disease. J Neurol

20.

Lawrence AD, Hodges JR, Rosser AE, Kershaw A, Ffrench-Constant C, Rubinsztein DC, Robbins TW, Sahakian BJ (1998) Evidence for specific cognitive deficits in preclinical Huntington’s disease. Brain 121(Pt 7):1329–1341CrossRefPubMed

21.

Lawrence AD, Sahakian BJ, Rogers RD, Hodge JR, Robbins TW (1999) Discrimination, reversal, and shift learning in Huntington’s disease: mechanisms of impaired response selection. Neuropsychologia 37:1359–1374CrossRefPubMed

22.

Lopez-Sendon JL, Royuela A, Trigo P, Orth M, Lange H, Reilmann R, Keylock J, Rickards H, Piacentini S, Squitieri F, Landwehrmeyer B, Witjes-Ane MN, Jurgens CK, Roos RA, Abraira V, de Yebenes JG, European HDN (2011) What is the impact of education on Huntington’s disease? Mov Disord 26:1489–1495CrossRefPubMed

23.

Melik Z, Kobal J, Cankar K, Strucl M (2012) Microcirculation response to local cooling in patients with Huntington’s disease. J Neurol 259:921–928CrossRefPubMed

24.

Minson CT (2010) Thermal provocation to evaluate microvascular reactivity in human skin. J Appl Physiol 109:1239–1246PubMedCentralCrossRefPubMed

25.

Orth M, Handley OJ, Schwenke C, Dunnett SB, Craufurd D, Ho AK, Wild E, Tabrizi SJ, Landwehrmeyer GB, Investigators of the European huntington’s disease N (2010) Observing Huntington’s disease: the European Huntington’s disease network’s registry. PLoS Curr 2:RRN1184PubMed

26.

Papp KV, Snyder PJ, Mills JA, Duff K, Westervelt HJ, Long JD, Lourens S, Paulsen JS (2013) Measuring executive dysfunction longitudinally and in relation to genetic burden, brain volumetrics, and depression in prodromal Huntington disease. Arch Clin Neuropsychol 28:156–168PubMedCentralCrossRefPubMed

27.

Paulsen JS, Langbehn DR, Stout JC, Aylward E, Ross CA, Nance M, Guttman M, Johnson S, Macdonald M, Beglinger LJ, Duff K, Kayson E, Biglan K, Shoulson I, Oakes D, Hayden M (2008) Detection of Huntington’s disease decades before diagnosis: the Predict-HD study. J Neurol Neurosurg Psychiatry 79:874–880PubMedCentralCrossRefPubMed

28.

Paulsen JS, Magnotta VA, Mikos AE, Paulson HL, Penziner E, Andreasen NC, Nopoulos PC (2006) Brain structure in preclinical Huntington’s disease. Biol Psychiatry 59:57–63CrossRefPubMed

29.

Petersen A, Bjorkqvist M (2006) Hypothalamic-endocrine aspects in Huntington’s disease. Eur J Neurosci 24:961–967CrossRefPubMed

30.

Pirogovsky E, Goldstein J, Peavy G, Jacobson MW, Corey-Bloom J, Gilbert PE (2009) Temporal order memory deficits prior to clinical diagnosis in Huntington’s disease. J Int Neuropsychol Soc 15:662–670CrossRefPubMed

31.

Rosas HD, Tuch DS, Hevelone ND, Zaleta AK, Vangel M, Hersch SM, Salat DH (2006) Diffusion tensor imaging in presymptomatic and early Huntington’s disease: selective white matter pathology and its relationship to clinical measures. Mov Disord 21:1317–1325CrossRefPubMed

32.

Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 57:925–935CrossRefPubMed

33.

Scoville WB, Milner B (1957) Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 20:11–21PubMedCentralCrossRefPubMed

34.

Shirbin CA, Chua P, Churchyard A, Hannan AJ, Lowndes G, Stout, JC (2012) The relationship between cortisol and verbal memory in the early stages of Huntington’s disease. J Neurol

35.

Simonin C, Duru C, Salleron J, Hincker P, Charles P, Delval A, Youssov K, Burnouf S, Azulay JP, Verny C, Scherer C, Tranchant C, Goizet C, Debruxelles S, Defebvre L, Sablonniere B, Romon-Rousseaux M, Buee L, Destee A, Godefroy O, Durr A, Landwehrmeyer B, Network RSOTEHSD, Bachoud-Levi AC, Richard F, Blum D, Krystkowiak P, Huntington French Speaking N (2013) Association between caffeine intake and age at onset in Huntington’s disease. Neurobiol Dis 58:179–182CrossRefPubMed

36.

Solomon AC, Stout JC, Johnson SA, Langbehn DR, Aylward EH, Brandt J, Ross CA, Beglinger L, Hayden MR, Kieburtz K, Kayson E, Julian-Baros E, Duff K, Guttman M, Nance M, Oakes D, Shoulson I, Penziner E, Paulsen JS (2007) Verbal episodic memory declines prior to diagnosis in Huntington’s disease. Neuropsychologia 45:1767–1776PubMedCentralCrossRefPubMed

37.

Stout JC, Paulsen JS, Queller S, Solomon AC, Whitlock KB, Campbell JC, Carlozzi N, Duff K, Beglinger LJ, Langbehn DR, Johnson SA, Biglan KM, Aylward EH (2011) Neurocognitive signs in prodromal Huntington disease. Neuropsychology 25:1–14PubMedCentralCrossRefPubMed

38.

Tabrizi SJ, Reilmann R, Roos RA, Durr A, Leavitt B, Owen G, Jones R, Johnson H, Craufurd D, Hicks SL, Kennard C, Landwehrmeyer B, Stout JC, Borowsky B, Scahill RI, Frost C, Langbehn DR, Investigators T-H (2012) Potential endpoints for clinical trials in premanifest and early Huntington’s disease in the TRACK-HD study: analysis of 24 month observational data. Lancet Neurol 11:42–53CrossRefPubMed

39.

Tabrizi SJ, Scahill RI, Durr A, Roos RA, Leavitt BR, Jones R, Landwehrmeyer GB, Fox NC, Johnson H, Hicks SL, Kennard C, Craufurd D, Frost C, Langbehn DR, Reilmann R, Stout JC, Investigators T-H (2011) Biological and clinical changes in premanifest and early stage Huntington’s disease in the TRACK-HD study: the 12-month longitudinal analysis. Lancet Neurol 10:31–42CrossRefPubMed

40.

Tabrizi SJ, Scahill RI, Owen G, Durr A, Leavitt BR, Roos RA, Borowsky B, Landwehrmeyer B, Frost C, Johnson H, Craufurd D, Reilmann R, Stout JC, Langbehn DR (2013) Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington’s disease in the TRACK-HD study: analysis of 36-month observational data. Lancet Neurol 12:637–649CrossRefPubMed

41.

Tabrizi SJ, Scahill RI, Owen G, Durr A, Leavitt BR, Roos RA, Borowsky B, Landwehrmeyer B, Frost C, Johnson H, Craufurd D, Reilmann R, Stout JC, Langbehn DR, Investigators T-H (2013) Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington’s disease in the TRACK-HD study: analysis of 36-month observational data. Lancet Neurol 12:637–649CrossRefPubMed

42.

Thieben MJ, Duggins AJ, Good CD, Gomes L, Mahant N, Richards F, McCusker E, Frackowiak RS (2002) The distribution of structural neuropathology in pre-clinical Huntington’s disease. Brain 125:1815–1828CrossRefPubMed

43.

van den Bogaard SJ, Dumas EM, Acharya TP, Johnson H, Langbehn DR, Scahill RI, Tabrizi SJ, van Buchem MA, van der Grond J, Roos RA (2011) Early atrophy of pallidum and accumbens nucleus in Huntington’s disease. J Neurol 258:412–420PubMedCentralCrossRefPubMed

44.

Watkins LH, Rogers RD, Lawrence AD, Sahakian BJ, Rosser AE, Robbins TW (2000) Impaired planning but intact decision making in early Huntington’s disease: implications for specific fronto-striatal pathology. Neuropsychologia 38:1112–1125CrossRefPubMed

Titel: Progress in Huntington’s disease: the search for markers of disease onset and progression
verfasst von: Sarah Mason
Roger A. Barker
Publikationsdatum: 01.08.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology / Ausgabe 8/2015
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-015-7700-0

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2015

Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome in a patient with the R232C TRPV4 mutation

Eye-tracking controlled cognitive function tests in patients with amyotrophic lateral sclerosis: a controlled proof-of-principle study

Erratum to: Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome in a patient with the R232C TRPV4 mutation

Hereditary spastic paraplegia type 11 with a very late onset

Neuroimaging evidence of gray and white matter damage and clinical correlates in progressive supranuclear palsy