Extrapyramidal Diseases: Huntington’s Disease




© Springer-Verlag Italia 2015
Angelo Sghirlanzoni, Giuseppe Lauria and Luisa Chiapparini (eds.)Prognosis of Neurological Diseases10.1007/978-88-470-5755-5_30


30. Extrapyramidal Diseases: Huntington’s Disease



Franco Valzania 


(1)
Neurological Department, Azienda Sanitaria of Modena, Viale giardini 1355, Modena, 41100, Italy

 



 

Franco Valzania



Keywords
Huntington’s diseaseHuntingtin proteinChoreic movementPrognosis of Huntington’s chorea



Key Facts





  • Definitions – Huntington’s disease (HD) is an autosomal dominant neurodegenerative movement disorder.


  • Demographic – Prevalence 0.2–10/100,000 with a geographical gradient from south to north.


  • Clinical feature – Progressive condition characterized by involuntary “choreic” movements, cognitive deficit, and psychiatric features.


  • Pathogenesis – Expansion of a CAG sequence in the coding region of the huntingtin (Htt) gene in exon 1 of 4p16.3 chromosome.


  • Diagnostic Markers



    • Genetics – CAG trinucleotide repeats in chromosome 4p16.3 ≥ 36 (normal < 36).


    • Imaging – TC and MRI scans show progressive striatal atrophy, which can precede motor symptoms. Late generalized cerebral atrophy. FDG-PET: selective striatal hypometabolism even preceding of years hypotrophy at MRI.


    • Neurophysiology – Polygraphic recording of multiple brief muscle contractions not related to EEG activity. Reduced corticospinal excitability on TMS study.


  • Top differential diagnoses – Dentato-rubro-pallido-luysian atrophy, ataxia telangiectasia, SCA17, neuroacanthocitosys; benign familial, Sydenham’s and drug-induced, immuno-mediated chorea.


  • Therapy – No disease-modifying treatments; symptomatic treatment of choreic movements is based on neuroleptics, benzodiazepines, and tetrabenazine. Conventional therapy for psychiatric disorders.


  • Prognosis – Invariably fatal outcome. Mean survival 15–20 years.


Abbreviations

CAGn, number (n) of trinucleotide repeats; HD, Huntington’s disease; Htt, huntingtin; TMS, transcranial magnetic stimulation; Unified Huntington’s Disease Rating Scale, UHDRS.


30.1 Definition and Clinical Features


Huntington’s disease (HD) (synonym chorea major) is an autosomal dominant neurodegenerative disease characterized by involuntary “choreic” movements, with cognitive deficit and psychiatric features. It is caused by the expansion of a CAG sequence in the coding region of the huntingtin gene (IT15) located in the short arm of chromosome 4, in its N-terminal part [1].


30.2 Epidemiology


The prevalence varies in relation to the geographic region with highest incidence (5–10 cases per 100,000 inhabitants) in North America, central and northern Europe, and Oceania; 2–5 cases/100,000 in southern Europe, Asia, and South Africa; and <1:100,000 in North Africa [2].

HD more often begins in the fourth or fifth decade but can occur at any time, from the first year of age (“ juvenile variant”), even up to the eighth decade (“late-onset chorea”). CAGn repeats influences the age of clinical debut with an inverse relationship with the age of onset [3]. Earlier onset in successive generations (anticipation) is known to be attributable to increasing lengths of the CAG repeat sequence.


30.3 Clinical Features


In the years immediately preceding the diagnosis, some behavioral, cognitive or motor changes may occur but could be so mild as to remain undetected by the same subject or family [4].

At the diagnostic stage of Huntington’s disease, a typical triad of symptoms characterized by motor disorders, behavioral and cognitive deficits of subcortical type is evident [5]. Choreic movements are the marker of the disease and are observed in two thirds of cases, often combined with motor incoordination and persistence.

Chorea tends to worsen over time until a plateau, after which abnormal movements can decrease at the onset of dystonia and rigidity, typical of later and final phases. Only in juvenile cases (variant of Westfall), rigidity and dystonia are observed from the beginning.

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Nov 10, 2016 | Posted by in NEUROLOGY | Comments Off on Extrapyramidal Diseases: Huntington’s Disease

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