Table 1
Brain Regions Implicated in Restless Legs Syndrome
| Brain Region | Abnormality |
|---|---|
| Prefrontal cortex | ↑ activity (fMRI),18 ↓ gray matter density (voxel morphometry MRI)27 |
| Medial frontal | ↑ gray matter density28; ↔ gray matter density (voxel morphometry MRI)29 |
| Precentral gyrus | ↑ activity (fMRI),18 ↓ intra-cortical inhibition (TMS)30; ↑ gray matter (voxel morphometry MRI)31 |
| Postcentral gyrus | ↑ activity (fMRI)18; ↑ gray matter (voxel morphometry MRI)31 |
| Anterior cingulate cortex | ↑ activity (fMRI),18 ↔ gray matter density (Voxel morphometry MRI),32 ↓ white matter volume (voxel morphometry MRI)33 |
| Posterior cingulate cortex | ↑ activity (fMRI)18 |
| Whole brain | ↔ gray matter (voxel morphometry MRI)18,34 |
| Putamen | ↓ iron staining (pathology),15,16,35 ↓ iron (MRI),12 ↓ dopamine-2 binding (PET),36 ↓ dopamine-2 receptor levels (pathology)37 |
| Substantia nigra | ↓ iron (pathology),15,16,35 ↓ iron (MRI),12,13 ↓ iron (phase imaging),22 ↑ tyrosine hydroxylase levels (pathology)37 |
| Caudate | ↓ iron staining (pathology), ↓ iron (MRI)14 |
| Pons, medulla | ↔ Serotonin transporter38 |
| Thalamus | ↑ activity (fMRI),17,18 ↑ gray matter density pulvinar (Voxel morphometry MRI),39 ↔ NAA,40 ↑ glutamate (MRS),40 ↓ β-endorphin positive cells (pathology),41 ↓ iron (MRI)14 |
| Cerebellum | ↑ activity (fMRI),17,18 ↓ gray matter density (voxel morphometry MRI)27 |
Figure 1
Periodic Limb Movements During Sleep Demonstrated By Polysomnography. Periodic limb movements during sleep are displayed as demonstrated by periodically occurring (every 20–30 seconds) activations of anterior tibialis electromyography. Also noticeable in this schematic are activations of electroencephalography, in the form of synchronous cortical firing (K-complexes) and acceleration of heart rate as evidenced by shortening of the R-R interval on electrocardiography.
Table 2
Genes Implicated in RLS and PLMS: Cohort, Location, and Function
| Gene | Chromosome | Function | SNP | Cohort |
|---|---|---|---|---|
| BTBD9 | 6p21.2 | Synaptic plasticity, learning | rs3923809, rs9296249, rs9357271 | Iceland,103 United States,106 Germany,104 Austria,114 Canada,104 Czech Republic,114 Finland,114 Korea115 |
| MEIS1 | 2p14 | Homeobox gene, limb formation, motor neuron connectivity | Rs2300478 | Germany,104 Austria,114 Czech Republic,114 Canada,104 United States106 |
| PTPRD | 9p23-24 | Protein tyrosine phosphatase regulates cell growth, mitosis | rs4626664, rs1975197 | Korea,115 United States116 |
| MAP2K5 | 15q23 | Protein kinase involved in cell proliferation | Rs12593813, rs11635424, rs4489954, rs3784709, rs1026732, rs6494696 | Germany,104 Austria,114 Czech Republic,114 Canada,104 United States106 |
| TOX3 | 16q12.1 | Transcription factor | Rs3104767, rs3104788 | Germany117 |