Paroxysmal kinesigenic dyskinesia

Paroxysmal kinesigenic dyskinesias are often inherited in an autosomal dominant fashion and several genes have now been identified where mutations can cause this disease. The genes typically code for proteins known to be involved in synaptic transmission, ion channels or ion transporters. The first gene to be identified was the PRRT2 gene on chromosome 16, found in 2011 to be the cause of the disease in some patients. The mutations in this gene included a nonsense mutation identified in the genome of one family and an insertion mutation identified in the genome of another family. Researchers found PRRT2 mutations in 10 of 29 sporadic cases affected with PKD, thus suggests PRRT2 is the gene mutated in a subset of PKD and PKD is genetically heterogeneous. Later reports have identified the genes SCN8A, CHRNA4, and SLC16A2 as further causes of PKD. ==Pathophysiology==

The pathophysiology of PKD is not fully explained. A few mechanisms have been suggested thus far: • GABA dysregulation • Abnormal breakdown of dopamine in the basal ganglia • Dysfunction of the substantia nigra • A form of epilepsy The researchers also subtracted the ictal from the postictal scans, and saw increased blood flow in the thalamus. They ultimately suggested that hyperactive blood flow in this area could be causing the pathophysiology of PKD. This study, however, was only performed on one patient, and would need to be replicated many more times in order to be generalized to the population of PKD patients. Other SPECT studies have been cited showing hyperactivity in the basal ganglia. fMRI studies In a study by Zhou et al., the researchers performed fMRI studies on PKD patients, and analyzed the differences between the amplitude low frequency fluctuations (ALFF) of the patients. They found that the left postcentral gyrus and the bilateral putamen had increased ALFF in PKD patients. The researchers concluded that the hyperactivity in these regions suggested that there is a dysfunction in the basal ganglia-thalamo-cortical circuit in PKD. This circuit is part of the motor control circuit in the brain, making it a reasonable place for abnormality in a movement disorder, but again, researchers are still unsure of the role these differences they found play in the disease pathology. Diffusion tensor imaging Diffusion tensor imaging (DTI) displays physical alterations in the brain that may not be seen on regular MRI. In one study researchers found that some of the patients had abnormalities in their thalamus. However, this does not prove that all patients have abnormalities in their thalamus. Other cases are cited, including a patient who developed a similar paroxysmal dyskinesia after a thalamic infarction, implicating that an abnormality in the thalamus of individuals could contribute to PKD. It is not fully known, however, what role a thalamic abnormality plays in the disease pathophysiology. ==Diagnosis==

Paroxysmal kinesigenic dyskinesia is diagnosed using a strict set of guidelines. These criteria were studied and confirmed by Bruno et al. in a study of 121 individuals with PKD. Additionally, PKD can almost always be managed with drug therapy, while PNKD is not as responsive to anticonvulsants. PED, on the other hand, separates itself from PKD in that it is caused by prolonged exercise. Attacks from PED will cease soon after exercise is stopped. ==Treatment==

Almost all patients respond positively to antiepileptic (anticonvulsant) drugs. One of the drugs most often mentioned in the literature is carbamazepine, and is the most widely used drug for treating PKD. Other anticonvulsants like valproic acid, phenytoin and clonazepam are common alternatives. Other categories of drugs have also been used, such as dopamine affecting drugs like Levodopa or Tetrabenazine. Individuals with the disorder can also modify their behavior to lessen their attacks without the influence of drug therapy. For example, decreasing stress to avoid precipitants can help patients decrease the number of attacks. In addition, avoiding any sudden movements can also prevent an attack. In order to prevent an attack, some individuals use their auras as a warning, while others purposefully perform slow gestures or movements prior to a triggering movement. Many, if not most, individuals end up growing out of the attacks with age, even without medicinal therapy, but some patients will go back to having attacks after a period of remission. In regards to secondary PKD, treatment of the primary condition can lessen the PKD attacks in those individuals. ==History ==

A movement disorder similar to PKD was first mentioned in research literature in 1940 by Mount and Reback. They described a disorder consisting of attacks of involuntary movements but unlike PKD, the attacks lasted minutes to hours and were found to be caused by alcohol or caffeine intake. ==See also==