PAROXYSMAL DYSKINESIAS

Abstract

Paroxysmal dyskinesias are hyperkinetic conditions, usually of the form of dystonia or choreoathetosis, that appear repeatedly and paroxysmally, usually following specific stimuli. A number of etiologies, such as specific drugs, or metabolic, toxic, infectious or imflammatory conditions can lead to secondary paroxysmal dyskinesias. Here we refer to idiopathic, mostly familial forms of paroxysmal dyskinesias that have a genetic basis. They are divided into 3 main categories, based on the eliciting stimulus. These are: Paroxysmal Kinesogenic Dyskinesias (PKD), Paroxysmal Non-Kinesogenic Dyskinesias (PNKD) and Paroxysmal Exercise-Induced Dyskinesias (PED). In most cases, there is a correlation with the genetic defects that lead to the disease, in particular PRRT2 (that encodes for the corresponding presynaptic protein) for PKD, MR1 (that also encodes for the corresponding presynaptic protein) for PNKD, and SLC2Α1 (that encodes for the Glucose Transporter 1, Glut1, in the Central Nervous System) for PED. Nevertheless, there is some overlap, while other genetic defects may also play a role. Lately, paroxysmal dyskinesias due to ADCY5 mutations have been included in the differential diagnosis of Paroxysmal Dyskinesias, as they characteristically worsen with sleepiness or relaxation. Usually paroxysmal Dyskinesias appear in a child who is otherwise normal, however there may be comorbidity with epilepsy or other paroxysmal conditions. Therapy is based on anticonvulsants and benzodiazepines, while in the case of PED due to Glut1 deficiency the ketogenic diet may also be helpful.