Introduction: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG expansion in the HTT gene and characterized by motor symptoms (chorea), cognitive impairment and psychiatric manifestations. It usually has onset in adult life between the ages of 30 and 50, and leads to death within 17-20 years. When onset falls outside the usual age spectrum, diagnosis may be more challenging and prognosis may be different. The term ‘late-onset HD’, encompassed in earlier papers all cases with symptoms onset above age 60. There are few reports that have focused specifically on late-onset HD. They have concluded that motor problems are predominant, cognitive decline is mild, psychiatric manifestations are rare, and that disease progression is slower. However, these were purely observational studies in which no comparisons were made with classic-onset HD. Since the characterization of HD is important, mainly in the view of the risk for offspring, also in the case of late onset, we analysed the spectrum of clinical, cognitive and behavioural features in HD patients subdivided according to the age at onset, as specified below. Methods: from 2004 to 2015 we analyzed clinical, cognitive and behavioural characteristics (UHDRS I,II,III scale) of a cohort of 66 patients with HD at the diagnosis (T0) and at the follow up (T1) and with a CAG expansion between 40 and 42. We divided patients on the base of onset disease: - 37 patients with classic onset (CO) ≤59 years: 17 F and 20 M. 6 patients with 40 CAG, 10 patients with 41 CAG, 21 patients with 42 CAG. 33 patients had a positive family history for HD (13 maternal history, 20 paternal history). 32 patients had a 1-2 stage of disease, 5 patients had a 3-4 stage of disease. - 29 patients with late onset (LO) ≥ 60 years: 18 F and 11 M. 11 patients with 40 CAG, 10 patients with 41 CAG, 8 patients with 42 CAG. 20 patients had a positive family history for HD (9 maternal history, 11 paternal history). 22 patients had a 1-2 stage of disease, 7 patients had a 3-4 stage of disease. The age at onset was defined as the age at which the first motor symptoms became clearly manifest. We investigated behavioural, cognitive or mood disorders (depression) associated to motor symptoms at the disease’s onset and we divided onset symptoms in: motor (M), motor + behavioural (M/P), motor + cognitive (M/C) or motor + behavioural + cognitive (M/C/P). 25 CO patients had only M onset, 12 M+ (1 patient M/C, 8 patients M/P, 3 M/P/C); 22 LO patients had only M onset, 7 M+ (2 patient M/C, 5 patients M/P). Statistic: The data were analyzed using chi-square, Fisher’s test, T-test, Pearson’s correlation coefficient as appropriate. Kaplan Meier analysis was used to assess disease progression. Results: a statistically significant difference was observed in absence of family history in LO group (P 0.0403). No differences were observed in type of transmission. Frequencies of onset symptoms (M,M/P,M/C,M/C/P), stage at the diagnosis and mood disorder (depression) before motor onset were not significantly different in two groups. A significant inverse correlation between CAG repeat size and age at onset was observed only for the upper allele (P 0.0403). No significant differences were found in clinical, behavioral, cognitive (UHDRS I,II,III) characteristics, TFC and FA between two groups at the diagnosis (T0) and at the FU (T1). No difference in disease progression was found in two groups. Discussion: A positive family history suggestive of HD, remains a helpful clue in diagnosing classic-onset HD. Previous studies on late-onset HD have suggested that motor disturbance (chorea) is the predominant early manifestation of late onset. In our cohort no clinical differences at diagnosis were observed in two groups. Similarly, the frequency of cognitive impairment and psychiatric manifestations at onset or at presentation was equivalent in late-onset and classic-onset HD patients. Previous reports have concluded that late-onset HD is relatively mild with slower progression compared to mid-life onset HD. To this regard, our findings in fact suggest that in terms of Total Functional Capacity, functional assessment and stage of disease, prognosis of late-onset HD is by no means better or more mildly progressing compared to classic onset HD. Conclusion: our findings confirm that there are no clinical, cognitive, and psychiatric differences at diagnosis and at FU in two groups of patients. The prognosis of late-onset HD is not better compared to CO. Age of onset is only “better” of late onset.

MALATTIA DI HUNTINGTON AD ESORDIO TARDIVO:ENTITA¿ CLINICA DISTINTA? / E. Capiluppi ; tutor: C. Mariani ; coordinatore: R. L. Weinstein. - : . DIPARTIMENTO DI SCIENZE BIOMEDICHE E CLINICHE "L. SACCO", 2015 Nov 19. ((28. ciclo, Anno Accademico 2015. [10.13130/capiluppi-elisa_phd2015-11-19].

MALATTIA DI HUNTINGTON AD ESORDIO TARDIVO:ENTITA¿ CLINICA DISTINTA?

E. Capiluppi
2015

Abstract

Introduction: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG expansion in the HTT gene and characterized by motor symptoms (chorea), cognitive impairment and psychiatric manifestations. It usually has onset in adult life between the ages of 30 and 50, and leads to death within 17-20 years. When onset falls outside the usual age spectrum, diagnosis may be more challenging and prognosis may be different. The term ‘late-onset HD’, encompassed in earlier papers all cases with symptoms onset above age 60. There are few reports that have focused specifically on late-onset HD. They have concluded that motor problems are predominant, cognitive decline is mild, psychiatric manifestations are rare, and that disease progression is slower. However, these were purely observational studies in which no comparisons were made with classic-onset HD. Since the characterization of HD is important, mainly in the view of the risk for offspring, also in the case of late onset, we analysed the spectrum of clinical, cognitive and behavioural features in HD patients subdivided according to the age at onset, as specified below. Methods: from 2004 to 2015 we analyzed clinical, cognitive and behavioural characteristics (UHDRS I,II,III scale) of a cohort of 66 patients with HD at the diagnosis (T0) and at the follow up (T1) and with a CAG expansion between 40 and 42. We divided patients on the base of onset disease: - 37 patients with classic onset (CO) ≤59 years: 17 F and 20 M. 6 patients with 40 CAG, 10 patients with 41 CAG, 21 patients with 42 CAG. 33 patients had a positive family history for HD (13 maternal history, 20 paternal history). 32 patients had a 1-2 stage of disease, 5 patients had a 3-4 stage of disease. - 29 patients with late onset (LO) ≥ 60 years: 18 F and 11 M. 11 patients with 40 CAG, 10 patients with 41 CAG, 8 patients with 42 CAG. 20 patients had a positive family history for HD (9 maternal history, 11 paternal history). 22 patients had a 1-2 stage of disease, 7 patients had a 3-4 stage of disease. The age at onset was defined as the age at which the first motor symptoms became clearly manifest. We investigated behavioural, cognitive or mood disorders (depression) associated to motor symptoms at the disease’s onset and we divided onset symptoms in: motor (M), motor + behavioural (M/P), motor + cognitive (M/C) or motor + behavioural + cognitive (M/C/P). 25 CO patients had only M onset, 12 M+ (1 patient M/C, 8 patients M/P, 3 M/P/C); 22 LO patients had only M onset, 7 M+ (2 patient M/C, 5 patients M/P). Statistic: The data were analyzed using chi-square, Fisher’s test, T-test, Pearson’s correlation coefficient as appropriate. Kaplan Meier analysis was used to assess disease progression. Results: a statistically significant difference was observed in absence of family history in LO group (P 0.0403). No differences were observed in type of transmission. Frequencies of onset symptoms (M,M/P,M/C,M/C/P), stage at the diagnosis and mood disorder (depression) before motor onset were not significantly different in two groups. A significant inverse correlation between CAG repeat size and age at onset was observed only for the upper allele (P 0.0403). No significant differences were found in clinical, behavioral, cognitive (UHDRS I,II,III) characteristics, TFC and FA between two groups at the diagnosis (T0) and at the FU (T1). No difference in disease progression was found in two groups. Discussion: A positive family history suggestive of HD, remains a helpful clue in diagnosing classic-onset HD. Previous studies on late-onset HD have suggested that motor disturbance (chorea) is the predominant early manifestation of late onset. In our cohort no clinical differences at diagnosis were observed in two groups. Similarly, the frequency of cognitive impairment and psychiatric manifestations at onset or at presentation was equivalent in late-onset and classic-onset HD patients. Previous reports have concluded that late-onset HD is relatively mild with slower progression compared to mid-life onset HD. To this regard, our findings in fact suggest that in terms of Total Functional Capacity, functional assessment and stage of disease, prognosis of late-onset HD is by no means better or more mildly progressing compared to classic onset HD. Conclusion: our findings confirm that there are no clinical, cognitive, and psychiatric differences at diagnosis and at FU in two groups of patients. The prognosis of late-onset HD is not better compared to CO. Age of onset is only “better” of late onset.
MARIANI, CLAUDIO
WEINSTEIN, ROBERTO LODOVICO
Huntington's disease; late onset; UHDRS scale
Settore MED/26 - Neurologia
MALATTIA DI HUNTINGTON AD ESORDIO TARDIVO:ENTITA¿ CLINICA DISTINTA? / E. Capiluppi ; tutor: C. Mariani ; coordinatore: R. L. Weinstein. - : . DIPARTIMENTO DI SCIENZE BIOMEDICHE E CLINICHE "L. SACCO", 2015 Nov 19. ((28. ciclo, Anno Accademico 2015. [10.13130/capiluppi-elisa_phd2015-11-19].
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/330294
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