Dystonia--new advances in classification, genetics, pathophysiology and treatment

Dystonia is a heterogeneous movement disorder and has been defined as 'a syndrome of sustained muscle contractions, frequently causing twisted and repetitive movements, or abnormal postures'. The classification of dystonia has developed along with increasing knowledge, and different schemes have been suggested, including age at onset, body distribution, and etiology as the main differentiating factors. A revised definition and a new classification of dystonia have now been proposed by a group of leading dystonia experts and will be referred here. The discovery of the first two gene mutations causing primary generalized dystonia (DYT1-TOR1A and DYT6-THAP1) has facilitated studies on pathogenesis and pathophysiology of primary dystonias, by comparing neurophysiology between manifesting and non-manifesting carriers, and by studying the molecular biology of the mutant gene products. During recent years, several other gene mutations causing primary dystonia, dystonia-plus, and paroxysmal dystonia disorders have been discovered. Only during the last year, by the use of whole-exome sequencing techniques, mutations in three different genes in families with predominantly cervical dystonia were found, which may lead to improved insight into the pathogenesis also of the more frequent focal dystonias. Botulinum neurotoxin (BoNT) and deep brain stimulation (DBS) have revolutionized the symptomatic treatment for dystonia during the last two decades and continue to be refined to improve efficacy and expand their indications. Unfortunately, no progress has been made in the oral medication of dystonia. Current and future new insights into pathogenetic and pathophysiological mechanisms of dystonia will hopefully lead to improvement also in this area soon.