changing leucine to proline at the 265th amino acid position of the MYK88 protein thereby causing the protein to be continuously active in stimulating the same cell-activating pathways that Toll-like receptors activate intermittently and on a  physiologically basis); b) the CXCR4 gene (8% in IgM MGUS, 25% in IgM-related malignancies); and c) increased gene copy number due to chromosomal rearrangements (36% in IgM MGUS, 82% in IgM-related malignancies). It is clear that each cell type contributes to different features of IgM malignancies but not clear that clonal plasma cells are critical to the development or progression of IgM MGUS. In all events, IgM MGUS is diagnosed in individuals who have serum IgM levels less than 30 gram/liter; have less than 10% of nucleated bone marrow cells with the lymphoplasmacytic morphology, and have no symptoms or findings of end organ dysfunction attributed to Waldenström macroglobulinemia such as anemia, decreases in any white blood cell count, cold agglutinin disease, hyperviscosity of blood, lymphadenopathy, hepatomegaly, splenomegaly, peripheral neuropathy, cryoglobulinemia, or constitutional symptoms.There may be a modest increase in the incidence of IgM MGUS in people of African descent. A study of 213 individuals diagnosed with IgM MGUS found that 10% at 5 years and 24% in 15 years progressed to more serious IgM-related diseases including non-Hodgkin lymphoma, Waldenstorms macroglobulinemia, systemic amyloidosis, and chronic lymphocytic leukemia. A second long-term study of 116 individuals with IgM MGUS found a 15-fold increased risk of progressing to a lymphoid malignancy, mostly to Waldenstorms macroglobulinemia.
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. The age at onset is between 1 and 20 years old. The attacks of involuntary movements last less than one minute and have a known trigger, usually a sudden voluntary movement. For example, if a PKD patient stands up or begins walking after being sedentary for a period of time, or a person goes from a walk to a run, it can trigger an attack. Persons with PKD do not lose consciousness during attacks and have a full memory of the entire attack.