Neuropathological Comparison of Adult Onset and Juvenile Huntington’s Disease with Cerebellar Atrophy: A Report of a Father and Son

Latimer, Caitlin S.; Flanagan, Margaret E.; Cimino, Patrick J.; Jayadev, Suman; Davis, Marie Y.; Hoffer, Zachary S.; Montine, Thomas J.; Gonzalez‐Cuyar, Luis F.; Bird, Thomas D.; Keene, C. Dirk

doi:10.3233/jhd-170261

Cited by 30 publications

(41 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With particular focus on the study of SBMA, it should be noted that the AR polyQ tract length in each of these models far exceeds the longest found in patients [47]. The length of the polyQ tract can have important implications in the pathology mediated by a polyQ-disease-causing protein, as has been demonstrated in HD [186]. Because polyQ tract length can affect which tissues are affected (and to what degree), caution is warranted in the interpretation of tissue-specific effects in mice expressing AR with extraphysiological polyQ tract lengths.…”

Section: In Vivo Modelsmentioning

confidence: 99%

Molecular Mechanisms and Therapeutics for SBMA/Kennedy's Disease

Arnold

Merry

2019

Neurotherapeutics

View full text Add to dashboard Cite

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by a polyglutamine (polyQ) expansion in the androgen receptor (AR). Despite the fact that the monogenic cause of SBMA has been known for nearly 3 decades, there is no effective treatment for this disease, underscoring the complexity of the pathogenic mechanisms that lead to a loss of motor neurons and muscle in SBMA patients. In the current review, we provide an overview of the system-wide clinical features of SBMA, summarize the structure and function of the AR, discuss both gain-of-function and loss-of-function mechanisms of toxicity caused by polyQ-expanded AR, and describe the cell and animal models utilized in the study of SBMA. Additionally, we summarize previously conducted clinical trials which, despite being based on positive results from preclinical studies, proved to be largely ineffective in the treatment of SBMA; nonetheless, these studies provide important insights as researchers develop the next generation of therapies.

show abstract

Section: In Vivo Modelsmentioning

confidence: 99%

Molecular Mechanisms and Therapeutics for SBMA/Kennedy's Disease

Arnold

Merry

2019

Neurotherapeutics

View full text Add to dashboard Cite

show abstract

“…A evolução cursa com piora do quadro cognitivo, psiquiátrico e com surgimento de sintomatologia motora 4,7 . A família também pode relatar como primeiros sintomas motores dificuldade de deambular, quedas frequentes, bem como disartria 6,12,20,21,22 . A instabilidade postural em associação com quedas, sinais piramidais e regressão cognitiva pode levar ao diagnóstico diferencial de síndrome de regressão idiopática 22 .…”

Section: Dicussãounclassified

“…A DHJ é mais observada quando a herança é paterna 5,[9][10][11][12] e este fato pode ser explicado devido à maior instabilidade da repetição do trinucleotídeo CAG durante a espermatogênese se comparado à ovogênese 5,12 . A idade de manifestação da DHJ se apresenta inversamente proporcional à quantidade de repetições de CAG 4,7 , no entanto, ainda não há um consenso, pois outros fatores, além da quantidade de repetições, podem estar interligados com a idade de manifestação da doença 2 .…”

Section: Introductionunclassified

Manifestações neuropsicomotoras da doença de Huntington juvenil

Nogueira

Rocha

Vasconcelos

et al. 2019

Rev. Med. (São Paulo)

View full text Add to dashboard Cite

Nogueira LA, Rocha AEO, Vasconcelos LM, Figueiredo Junior JAB, Bragato SGR. Manifestações neuropsicomotoras da doença de Huntington juvenil: sinais e sintomas e achados de imagem / Neuropsychomotor manifestations of juvenile Huntington's disease: signs and symptoms and imaging findings. Rev Med (São Paulo). 2019 nov.-dez.;98(6):408-14. RESUMO: A Doença de Huntington Juvenil (DHJ) consiste na neurodegeneração de células nervosas causada pela formação da proteína alterada denominada huntingtina, acumuladano citoplasma e núcleo de neurônios, capaz de gerar morte progressiva destas células de forma mais evidente no corpo estriado, que engloba os núcleos caudado e putâmen. A variante juvenil da Doença de Huntington manifesta-se em pacientes com idades entre 0 a 20 anos, com variedade de distúrbios motores, cognitivos e comportamentais. Com o objetivo de estudar os mais prevalentes sinais, sintomas e achados de imagem, bem como as manifestações iniciais e a evolução sintomatológica ao decorrer da doença, foi realizada uma revisão integrativa de literaturas, incluindo o total de 25 artigos selecionados após a adequação de critérios de exclusão e inclusão. Após a análise dos dados, concluiu-se que os sintomas mais destacados foram rigidez muscular, disartria, convulsões, bradicinesia e disfunções cognitivas e comportamentais. Em se tratando de achados de imagem, prevaleceram atrofia de núcleos da base e cerebelo em pacientes com a doença mais avançada e diagnosticados em tempo maior.ABSTRACT: Juvenile Huntington's disease consists of neurodegeneration of nerve cells caused by the formation of the altered protein called huntingtin, accumulated in the cytoplasm and nucleus of neurons, capable of generating progressive death of these cells more clearly in the striatum, which includes the nuclei caudate and putamen. The juvenile variant of Huntington's disease manifests in patients aged 0 to 20 years, with a variety of motor, cognitive and behavioral disorders. In order to study the most prevalent signs, symptoms and imaging findings, as well as the initial manifestations and the symptomatic evolution during the course of the disease, an integrative literature review was carried out, including a total of 25 articles selected after the adequacy of criteria exclusion and inclusion. After analyzing the data, it was concluded that the most prominent symptoms were muscle stiffness, dysarthria, seizures, bradykinesia and cognitive and behavioral dysfunctions. In terms of imaging findings, atrophy of nuclei of the base and cerebellum prevailed in patients with the most advanced disease and diagnosed in greater time.

show abstract

“…All patients were males at the age of 4 to 17 years. They had a number of CAG repeats from 49 to 169, which correlated with the age of the onset and the severity of the disease -the greater the number of repeats, the earlier the disease began and had more severe course [3,[5][6][7]10,11]. For all forms, a triad of signs is characteristic: motor disorders, mental disorders and progressive dementia.…”

Section: T Stetsenko 1 O Savchenko 2 N Salan 2 I Holovatyukmentioning

confidence: 99%

“…The duration of the disease varies, but on average it is 15 years in the classical form, about 10 years in the juvenile form and 4-6 years in the children form. Mortality is 100% [7].…”

Section: T Stetsenko 1 O Savchenko 2 N Salan 2 I Holovatyukmentioning

confidence: 99%

Huntington's chorea in a child. The first description of the disease in Ukraine. Proper observation

Stetsenko¹,

Savchenko²,

Salan³

et al. 2019

MPU

View full text Add to dashboard Cite

10)-is an autosomal dominant neurodegenerative disease characterized by motor disorders (chorea in adults and akinetic rigid syndrome in children), mental disorders and dementia with progressive course and mortality of 100%. Aim of research. To present a unique case of Huntington's chorea diagnosed in a child at the age of 4 in the third generation in the family. This case is descri bed for the first time in Ukraine. Results of research. Girl at the age of 4 years and 7 months who has been admitted to the NCSH «OKHMATDIT» with complaints about linguistic and psychic skills loss, ambulation disorder, and periodic falls from her standing height, episodes of urinary incontinence and attacks. Child was born healthy. Mental deve lopment was appropriate with age. The first symptoms appeared at the age of 1 year while walking. Initially, a slight spastic lower paraparesis (walking on toes) was diagnosed. With time a spastic dyskinetic walking appeared, worse to the left. From the age of 4, the regress of psychic functions began (The inte rest in fairy tales disappeared. The child became inattentive, ceased to maintain herself, memory decreased). Furthermore regress of speech began with the formation of extrapyramidal dysarthria and the poverty of speech. At the same time, the ambulation worsened, generalized epileptic seizures appeared. It is necessary to emphasize the fact that the family anamnesis is burdened on the father`s line. Her father, grandfather, great grandmother on the father`s line had HD. Across pregnancy, testing of an amniotic fluid was conducted. 120 CAG repeats were detected. During the examination of the child the disruption of com munication was determined (the girl performs some simple commands), dysphasia, extrapyramidal dysarthria (pronounces some obscure words, no phrasal language). In the neurological status there is pseudobulbar syndrome (hypersalivation), deviation of the tongue to the right. The gait is spastic dystonic, worse to the left. Change in muscle tone by plastic type in arms and legs, more to the left; hyperkinesis in the fingers (athetosis), dystonia in the feet and feet clo nus. On the MRI there was a moderately expressed diffuse decrease in the volume of parenchyma of both cerebellar hemispheres, the deepening and expan sion of the cerebellar grooves, some thinning of the cerebellar stalks. Also there are no cerebellar tonsils, wide Magendie's foramen, and a moderately enlar ged cisterna magna. It is interesting to note that the MRI of cerebral hemispheres, basal ganglia is without pathological changes. The electroencephalogram revealed generalized high amplitude spike wave epileptic activity during the entire recording. At the age of 4 years, the molecular genetic analysis was re con ducted; the number of CAG repeats was 130. For the treatment of epilepsy, the girl received antiepileptic drugs (valproates, lamotrigine) at maximum doses with minimal effect. Conclusions. 1. Huntington's chorea is a severe autosomal dominant neurodegenerative disease with 100% mortality. 2. Geneti...

show abstract

Neuropathological Comparison of Adult Onset and Juvenile Huntington’s Disease with Cerebellar Atrophy: A Report of a Father and Son

Cited by 30 publications

References 29 publications

Molecular Mechanisms and Therapeutics for SBMA/Kennedy's Disease

Molecular Mechanisms and Therapeutics for SBMA/Kennedy's Disease

Manifestações neuropsicomotoras da doença de Huntington juvenil

Huntington's chorea in a child. The first description of the disease in Ukraine. Proper observation

Contact Info

Product

Resources

About