Differential diagnosis of chorea (guidelines of the German Neurological Society)

Abstract

Introduction Choreiform movement disorders are characterized by involuntary, rapid, irregular, and unpredictable movements of the limbs, face, neck, and trunk. These movements often initially go unnoticed by the affected individuals and may blend together with seemingly intended, random motions. Choreiform movements can occur both at rest and during voluntary movements. They typically increase in intensity with stress and physical activity and essentially cease during deep sleep stages. In particularly in advanced stages of Huntington disease (HD), choreiform hyperkinesia occurs alongside with dystonic postures of the limbs or trunk before they typically decrease in intensity. Summary or definition of the topic The differential diagnosis of HD can be complex. Here, the authors aim to provide guidance for the diagnostic process. This guidance was prepared for the German Neurological Society (DGN) for German-speaking countries. Recommendations Hereditary (inherited) and non-hereditary (non-inherited) forms of chorea can be distinguished. Therefore, the family history is crucial. However, even in conditions with autosomal-dominant transmission such as HD, unremarkable family histories do not necessarily rule out a hereditary form (e.g., in cases of early deceased or unknown parents, uncertainties in familial relationships, as well as in offspring of parents with CAG repeats in the expandable range (27–35 CAG repeats) which may display expansions into the pathogenic range). Conclusions The differential diagnosis of chorea can be challenging. This guidance prepared for the German Neurological Society (DGN) reflects the state of the art as of 2023.

A Man With Progressive Chorea and Abnormal Trunk Movements

“…In ChAc, the degeneration extends to involve the thalamus and substantia nigra as well [ 1 ]. The differential diagnosis of chorea in early adulthood includes Huntington’s disease, spinocerebellar ataxia, HDL2 (Huntington’s disease-like), neuroferritinopathy, Wilson’s disease, NA syndromes, VPS13A‑ and XK‑disease/McLeod, aceruloplasminemia, Niemann‑Pick type C disease, drug-induced, autoimmune (anti-NMDAR encephalitis) causes, and Lesch-Nyhan syndrome [ 11 ]. A distinctive feature of ChAc is the existence of self-mutilating habits, such as biting one's lips or tongue, or other self-mutilating actions, such as finger biting.…”

Distribution of the C9orf72 hexanucleotide repeat expansion in healthy subjects: a multicenter study promoted by the Italian IRCCS network of neuroscience and neurorehabilitation

“…It is noteworthy that in certain European populations, the hexanucleotide repeat expansion in C9orf72 has been identified as the most prevalent cause of phenocopies resembling Huntington's disease (HD) (10). In line with this, the German Neurological Society has officially recognized C9orf72 expansion alleles as a primary HD phenocopy in their guidelines for the differential diagnosis of chorea (11). Furthermore, the phenotypes associated with C9orf72 can vary significantly, even within the same family lineage, manifesting in diverse neurodegenerative presentations (12).…”