Anti-PNKD monoclonal antibody Made to order

Paroxysmal dyskinesias (PD) are a heterogeneous group of disorders characterized by sudden attacks of involuntary hyperkinetic movements. In rare cases PD can be symptomatic (e. g. of underlying lesions in the basal ganglia), but most forms have a genetic background. Based on the trigger factors, PD are clinically divided into kinesigenic (PKC/PKD/DYT10), nonkinesigenic (PNKD/DYT8) and exercise-induced (PED/DYT18) forms. The first genes have been described for PNKD (MR1) and PED (SLC2A1). Whereas the function of the MR1 protein is still poorly understood, mutations in SLC2A1 lead to a reduced transport of glucose across the blood-brain barrier. Recently, mutations in PRRT2-which seems to be important in the neuronal synaptic vesicular cycle-were described in patients with PKD. This review summarizes the clinical symptoms, brain imaging findings, pathophysiology and therapeutic options pertaining to the different PD.

The clinical, pathophysiological and genetic features of some of the paroxysmal movement disorders are reviewed. Paroxysmal kine-sigenic choreoathetosis/dyskinesias (PKC/PKD) is a condition in which brief and frequent dyskinetic attacks are provoked by sudden movement. PKC is more common in men and can be idiopathic (commonly familial) or due to a variety of causes. The pathophysiology of PKC is uncertain but it could be an ion-channel disorder. Antiepileptic drugs particularly carbamazepine are very helpful in a large proportion of cases. Paroxysmal exercise induced dystonia (PED) is a rare disorder manifesting as episodes of dystonia mostly affecting the feet induced by continuous exercise like walking or running. Although the initial cases were familial, there is a higher proportion of sporadic cases. The pathophysiology of FED is unknown and antiepileptic drugs are generally unhelpful. In paroxysmal dystonic choreoathetosis/non-kinesigenic dyskinesias (PDC/ PNKD) the attacks are of long duration and induced by variety of factors including coffee, tea, alcohol and fatigue but not by sudden movement. PDC can be idiopathic (familial or sporadic) or symptomatic due to a variety of causes. The gene for familial PDC has been linked in 2 families to chromosome 2 q close to a cluster of ion channel genes again suggesting that this disorder may also be a channelopathy. Other paroxysmal disorders include paroxysmal nocturnal dyskinesia, a form of frontal lobe epilepsy in some cases which may be familial with autosomal dominant inheritance (ADNFLE). The gene for ADNFLE in one family has been found to be a mutation in the neuronal acetylcholine receptor gene (CHRNA4) on chromosome 20q. Tonic spasms in multiple sclerosis and Sandiffers syndrome producing intermittent torticollis in infants and children are other paroxysmal movement disorders.