scholarly journals Endophenotypical drift in Huntington’s disease: a 5-year follow-up study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Marie N. N. Hellem ◽  
Rebecca K. Hendel ◽  
Tua Vinther-Jensen ◽  
Ida U. Larsen ◽  
Troels T. Nielsen ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Burden ◽  
Psychiatric Symptoms ◽  
Cag Repeat ◽  
Symptom Trajectories ◽  
Younger Age ◽  
Cardinal Symptoms ◽  
State Examination

Abstract Background Huntington’s disease (HD) is clinically characterized by progressing motor, cognitive and psychiatric symptoms presenting as varying phenotypes within these three major symptom domains. The disease is caused by an expanded CAG repeat tract in the huntingtin gene and the pathomechanism leading to these endophenotypes is assumed to be neurodegenerative. In 2012/2013 we recruited 107 HD gene expansion carriers (HDGECs) and examined the frequency of the three cardinal symptoms and in 2017/2018 we followed up 74 HDGECs from the same cohort to describe the symptom trajectories and individual drift between the endophenotypes as well as potential predictors of progression and remission. Results We found higher age to reduce the probability of improving on psychiatric symptoms; increasing disease burden score ((CAG-35.5) * age) to increase the risk of developing cognitive impairment; increasing disease burden score and shorter education to increase the risk of motor onset while lower disease burden score and higher Mini Mental State Examination increased the probability of remaining asymptomatic. We found 23.5% (N = 8) to improve from their psychiatric symptoms. Conclusions There is no clear pattern in the development of or drift between endophenotypes. In contrast to motor and cognitive symptoms we find that psychiatric symptoms may resolve and thereby not entirely be caused by neurodegeneration. The probability of improving from psychiatric symptoms is higher in younger age and advocates for a potential importance of early treatment.

scholarly journals Psychiatric morbidity and poor follow-up underlie suboptimal functional and survival outcomes in Huntington's disease

2020 ◽  
Author(s):  
Nikhil Ratna ◽  
Nitish L Kamble ◽  
Sowmya D V ◽  
Meera Purushottam ◽  
Pramod K Pal ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Tertiary Care ◽  
Psychiatric Morbidity ◽  
Cag Repeat ◽  
Duration Of Illness ◽  
Low Middle Income Countries

Abstract BACKGROUND: Huntington’s disease (HD), an inherited, often late-onset, neurodegenerative disorder, is considered to be a rare, orphan disease. Research into its genetic correlates and services for those affected are inadequate in most low-middle income countries, including India. The apparent ‘incurability’ often deters symptomatic and rehabilitative care, resulting in poor quality of life and sub-optimal outcomes. There are no studies assessing disease burden and outcomes from India. METHODS: We attempted to evaluate individuals diagnosed to have HD at our tertiary-care center between 2013 and 2016 for clinical symptoms, functionality, mortality, follow up status through a structured interview, clinical data from medical records and UHDRS-TFC scoring. RESULTS: Of the 144 patients, 25% were untraceable, and another 17 (11.8%) had already died. Mean age at death and duration of illness at the time of death, were 53 years and 7 years respectively, perhaps due to suicides and other comorbidities at an early age. The patients who could be contacted (n=81) were assessed for morbidity and total functional capacity (TFC). Mean CAG repeat length and TFC score were 44.2 and 7.5 respectively. Most individuals (66%) were in TFC stage I and II and could perhaps benefit from several interventions. The TFC score correlated inversely with duration of illness (p<0.0001). The majority were being taken care of at home, irrespective of the physical and mental disability. There was a high prevalence of psychiatric morbidity (91%) including suicidal tendency (22%). Three of the 17 who died had committed suicide, and several other families reported suicidal history in other family members. Only about half the patients (57%) maintained a regular clinical follow-up. CONCLUSIONS: This study demonstrates the poor follow-up rates, significant suicidality and other psychiatric symptoms, sub-optimal survival durations and functional outcomes highlighting the need for holistic care for the majority who appear to be amenable to interventions.

scholarly journals Psychiatric morbidity and poor follow-up underlie suboptimal functional and survival outcomes in Huntington's disease

2019 ◽  
Author(s):  
Nikhil Ratna ◽  
Nitish L Kamble ◽  
Sowmya D V ◽  
Meera Purushottam ◽  
Pramod K Pal ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Tertiary Care ◽  
Psychiatric Morbidity ◽  
Cag Repeat ◽  
Duration Of Illness ◽  
Low Middle Income Countries

Abstract BACKGROUND: Huntington’s disease (HD), an inherited, often late-onset, neurodegenerative disorder, is considered to be a rare, orphan disease. Research into its genetic correlates and services for those affected are inadequate in most low-middle income countries, including India. The apparent ‘incurability’ often deters symptomatic and rehabilitative care, resulting in poor quality of life and sub-optimal outcomes. There are no studies assessing disease burden and outcomes from India. METHODS: We attempted to evaluate individuals diagnosed to have HD at our tertiary-care center between 2013 and 2016 for clinical symptoms, functionality, mortality, follow up status through a structured interview, clinical data from medical records & UHDRS TFC scoring. RESULTS: Of the 144 patients, 25% were untraceable, and another 17 (11.8%) had already died. Mean age at and duration of illness at the time of death, were 53 years and 7 years respectively, which is much shorter than in Europe and USA. The patients who could be contacted (n=81) were assessed for symptomatic morbidity and total functional capacity (TFC). Mean CAG repeat length and TFC score were 44.2 and 7.5 respectively. Most individuals (66%) were in TFC stage I and II and could perhaps benefit from several interventions. The TFC score correlated inversely with duration of illness (p<0.0001). The vast majority were being taken care of at home, irrespective of the physical and mental disability. There was a high prevalence of psychiatric morbidity (91%) including suicidal tendency (22%). Three of the 17 who died had committed suicide, and many other families reported suicidal history in other family members. Only about half the patients (57%) maintained a regular clinical follow-up. CONCLUSIONS: This study demonstrates the poor follow-up rates, significant suicidality & other psychiatric symptoms, suboptimal survival durations and functional outcomes highlighting the need for holistic care for the majority who appear to be amenable for interventions.

scholarly journals Psychiatric morbidity and poor follow-up underlie suboptimal functional and survival outcomes in Huntington's disease

2019 ◽  
Author(s):  
Nikhil Ratna ◽  
Nitish L Kamble ◽  
Sowmya D V ◽  
Meera Purushottam ◽  
Pramod K Pal ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Tertiary Care ◽  
Psychiatric Morbidity ◽  
Cag Repeat ◽  
Duration Of Illness ◽  
Low Middle Income Countries

Abstract BACKGROUND: Huntington’s disease (HD), an inherited, often late-onset, neurodegenerative disorder, is considered to be a rare, orphan disease. Research into its genetic correlates and services for those affected are inadequate in most low-middle income countries, including India. The apparent ‘incurability’ often deters symptomatic and rehabilitative care, resulting in poor quality of life and sub-optimal outcomes. There are no studies assessing disease burden and outcomes from India. METHODS: We attempted to evaluate individuals diagnosed to have HD at our tertiary-care center between 2013 and 2016 for clinical symptoms, functionality, mortality, follow up status through a structured interview, clinical data from medical records & UHDRS TFC scoring. RESULTS: Of the 144 patients, 25% were untraceable, and another 17 (11.8%) had already died. Mean age at death and duration of illness at the time of death, were 53 years and 7 years respectively, perhaps due to suicides and other comorbidities at an early agewhich is much shorter than in Europe and USA. The patients who could be contacted (n=81) were assessed for morbid symptoms and total functional capacity (TFC). Mean CAG repeat length and TFC score were 44.2 and 7.5 respectively. Most individuals (66%) were in TFC stage I and II and could perhaps benefit from several interventions. The TFC score correlated inversely with duration of illness (p<0.0001). The vast majority were being taken care of at home, irrespective of the physical and mental disability. There was a high prevalence of psychiatric morbidity (91%) including suicidal tendency (22%). Three of the 17 who died had committed suicide, and many other families reported suicidal history in other family members. Only about half the patients (57%) maintained a regular clinical follow-up. CONCLUSIONS: This study demonstrates the poor follow-up rates, significant suicidality & other psychiatric symptoms, suboptimal survival durations and functional outcomes highlighting the need for holistic care for the majority who appear to be amenable for interventions.

scholarly journals Huntington’s Disease in a Patient Misdiagnosed as Conversion Disorder

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
João Machado Nogueira ◽  
Ana Margarida Franco ◽  
Susana Mendes ◽  
Anabela Valadas ◽  
Cristina Semedo ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Psychiatric Symptoms ◽  
Age Of Onset ◽  
Late Onset ◽  
Psychiatric Patients ◽  
Conversion Disorder ◽  
Cag Repeat ◽  
Clinical Assessments ◽  
Clinical Presentations

Huntington’s disease (HD) is an inherited, progressive, and neurodegenerative neuropsychiatric disorder caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide in Interested Transcript (IT) 15 gene on chromosome 4. This pathology typically presents in individuals aged between 30 and 50 years and the age of onset is inversely correlated with the length of the CAG repeat expansion. It is characterized by chorea, cognitive deficits, and psychiatric symptoms. Usually the psychiatric disorders precede motor and cognitive impairment, Major Depressive Disorder and anxiety disorders being the most common presentations. We present a clinical case of a 65-year-old woman admitted to our Psychiatric Acute Unit. During the 6 years preceding the admission, the patient had clinical assessments made several times by different specialties that focused only on isolated symptoms, disregarding the syndrome as a whole. In the course of her last admission, the patient was referred to our Neuropsychiatric Team, which made the provisional diagnosis of late-onset Huntington’s disease, later confirmed by genetic testing. This clinical vignette highlights the importance of a multidisciplinary approach to atypical clinical presentations and raises awareness for the relevance of investigating carefully motor symptoms in psychiatric patients.

scholarly journals Molecular mediators, environmental modulators and experience-dependent synaptic dysfunction in Huntington's disease.

2004 ◽  
Vol 51 (2) ◽  
pp. 415-430 ◽  
Author(s):  
Anthony J Hannan
Keyword(s):  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Environmental Enrichment ◽  
Molecular Mechanisms ◽  
Psychiatric Symptoms ◽  
Brain Regions ◽  
Cag Repeat ◽  
Autosomal Dominant Disorder ◽  
Gene Environment

Huntington's disease (HD) is an autosomal dominant disorder in which there is progressive neurodegeneration producing motor, cognitive and psychiatric symptoms. HD is caused by a trinucleotide (CAG) repeat mutation, encoding an expanded polyglutamine tract in the huntingtin protein. At least eight other neurodegenerative diseases are caused by CAG/glutamine repeat expansions in different genes. Recent evidence suggests that environmental factors can modify the onset and progression of Huntington's disease and possibly other neurodegenerative disorders. This review outlines possible molecular and cellular mechanisms mediating the polyglutamine-induced toxic 'gain of function' and associated gene-environment interactions in HD. Key aspects of pathogenesis shared with other neurodegenerative diseases may include abnormal protein-protein interactions, selective disruption of gene expression and 'pathological plasticity' of synapses in specific brain regions. Recent discoveries regarding molecular mechanisms of pathogenesis are guiding the development of new therapeutic approaches. Knowledge of gene-environment interactions, for example, could lead to development of 'enviromimetics' which mimic the beneficial effects of specific environmental stimuli. The effects of environmental enrichment on brain and behaviour will also be discussed, together with the general implications for neuroscience research involving animal models.

Abnormal gait and bradykinesia in the preclinical phase of Huntington's disease – psychogenic movement disorder?

2011 ◽  
Vol 23 (6) ◽  
pp. 315-317
Author(s):  
Witold Soltan ◽  
Emilia Sitek ◽  
Hubert Wichowicz ◽  
Dariusz Wieczorek ◽  
Jaroslaw Slawek
Keyword(s):  
Huntington's Disease ◽  
Movement Disorder ◽  
Huntington’S Disease ◽  
Rating Scale ◽  
Psychiatric Symptoms ◽  
Preclinical Phase ◽  
Abnormal Gait ◽  
Genetic Status ◽  
Psychogenic Movement Disorder

Soltan W, Sitek E, Wichowicz H, Wieczorek D, Slawek J. Abnormal gait and bradykinesia in the preclinical phase of Huntington's disease – psychogenic movement disorder?Objective: Psychiatric symptoms may occur in individuals at risk of Huntington's disease (HD) regardless of their genetic status. Psychopathological symptomatology is attributed to both genetic and environmental factors. In case of asymptomatic gene carriers, psychiatric symptoms may precede involuntary movements.Methods: We report the first case with abnormal gait and bradykinesia in preclinical adult HD. A 33-year-old woman blind to her mother's HD diagnosis and her own genetic status developed motor slowing and gait disturbance. The symptoms withdrew due to counselling and antidepressant medications. Subsequently, she was informed her own and her mother's genetic testing results, but 2-year follow-up did not reveal the onset of choreic movements, cognitive deterioration or depressive symptoms in the patient. Personality assessment (Minnesota Multiphasic Personality Inventory) and neurological examination results are presented, accompanied by 2-year follow-up data. Follow-up examination included Unified Huntington's Disease Rating Scale (motor, behaviour and function), Beck Depression Inventory, Hamilton Depression Rating Scale and neuropsychological assessment (trail-making test, Stroop test, verbal fluency trials, symbol digit modalities test, digit span, serial seven subtraction, Hopkins verbal learning test and nine-hole peg test).Conclusion: Motor abnormalities in individuals at risk of HD may be of psychogenic origin. It is a matter of debate if this psychogenic reaction presented as hypokinetic syndrome may be a result of choreic movements of her mother (hyperkinetic syndrome) and depression or if this psychogenic reaction represents the preclinical psychiatric abnormalities in an asymptomatic gene carrier preceding the onset of the disease.

Dementia due to Huntington’s disease

2020 ◽  
pp. 448-453
Author(s):  
Russell L. Margolis
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Psychiatric Symptoms ◽  
Cag Repeat ◽  
Causative Mutation ◽  
Clinical Onset ◽  
Key Features ◽  
Neurobiological Research ◽  
Clinical Triad ◽  
Near Future

Huntington’s disease (HD), first described in 1872, is perhaps the prototypical hereditary dementia and movement disorder. Key features include autosomal dominant inheritance, typically mid-life clinical onset, and a clinical triad of abnormal voluntary and involuntary movements, subcortical dementia, and psychiatric symptoms. The disease progresses inevitably, with death typically 15–20 years after onset. Neurodegeneration is most prominent in the striatum and cerebral cortex. The discovery of the causative mutation, an expanded CAG repeat in the gene huntingtin, has led to the development of reliable genetic testing for affected and at-risk individuals and an explosion of neurobiological research into HD pathogenesis. While present treatment of HD is limited to managing symptoms, there is considerable optimism that treatments to prevent, slow, or stop disease progression may be feasible in the near future.

The molecular biology of Huntington's disease

2001 ◽  
Vol 31 (1) ◽  
pp. 3-14 ◽  
Author(s):  
L. W. HO ◽  
J. CARMICHAEL ◽  
J. SWARTZ ◽  
A. WYTTENBACH ◽  
J. RANKIN ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cortical Neurons ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Intranuclear Inclusions ◽  
Progressive Dementia ◽  
Cellular Models

Background. Huntington's disease (HD) is a fatal neurodegenerative disorder with an autosomal dominant mode of inheritance. It leads to progressive dementia, psychiatric symptoms and an incapacitating choreiform movement disorder, culminating in premature death. HD is caused by an increased CAG repeat number in a gene coding for a protein with unknown function, called huntingtin. The trinucleotide CAG codes for the amino acid glutamine and the expanded CAG repeats are translated into a series of uninterrupted glutamine residues (a polyglutamine tract).Methods. This review describes the epidemiology, clinical symptomatology, neuropathological features and genetics of HD. The main aim is to examine important findings from animal and cellular models and evaluate how they have enriched our understanding of the pathogenesis of HD and other diseases caused by expanded polyglutamine tracts.Results. Selective death of striatal and cortical neurons occurs. It is likely that the HD mutation confers a deleterious gain of function on the protein. Neuronal intranuclear inclusions containing huntingtin and ubiquitin develop in patients and transgenic mouse models of HD. Other proposed mechanisms contributing to neuropathology include excitotoxicity, oxidative stress, impaired energy metabolism, abnormal protein interactions and apoptosis.Conclusions. Although many interesting findings have accumulated from studies of HD and other polyglutamine diseases, there remain many unresolved issues pertaining to the exact roles of intranuclear inclusions and protein aggregates, the mechanisms of selective neuronal death and delayed onset of illness. Further knowledge in these areas will inspire the development of novel therapeutic strategies.

scholarly journals Free carnitine and branched chain amino acids are not good biomarkers in Huntington’s disease

2020 ◽  
Vol 78 (2) ◽  
pp. 81-87
Author(s):  
Raphael Machado CASTILHOS ◽  
Marina Coutinho AUGUSTIN ◽  
José Augusto dos SANTOS ◽  
José Luiz PEDROSO ◽  
Orlando BARSOTTINI ◽  
...  
Keyword(s):  
Amino Acids ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Age Of Onset ◽  
Branched Chain Amino Acids ◽  
Free Carnitine ◽  
Cag Repeat ◽  
Isoleucine Leucine ◽  
Branched Chain

ABSTRACT Background: Huntington’s disease (HD), caused by an expanded CAG repeat at HTT, has no treatment, and biomarkers are needed for future clinical trials. Objective: The objective of this study was to verify if free carnitine and branched chain amino acids levels behave as potential biomarkers in HD. Methods: Symptomatic and asymptomatic HD carriers and controls were recruited. Age, sex, body mass index (BMI), age of onset, disease duration, UHDRS scores, and expanded CAG tract were obtained; valine, leucine, isoleucine, and free carnitine were measured. Baseline and longitudinal analysis were performed. Results: Seventy-four symptomatic carriers, 20 asymptomatic carriers, and 22 non-carriers were included. At baseline, valine levels were reduced in symptomatic and asymptomatic HD carriers when compared to non-carriers. No difference in free carnitine or isoleucine+leucine levels were observed between groups. BMI of symptomatic individuals was lower than those of non-carriers. Valine levels correlated with BMI. Follow-up evaluation was performed in 43 symptomatic individuals. UHDRS total motor score increased 4.8 points/year on average. No significant reductions in BMI or valine were observed, whereas free carnitine and isoleucine+leucine levels increased. Conclusions: Although valine levels were lower in HD carriers and were related to BMI losses observed in pre-symptomatic individuals, none of these metabolites seem to be biomarkers for HD.

Sign in / Sign up

Export Citation Format

Share Document