**11. Pathophysiology**

The pathophysiological mechanisms involved in RLS and PLMD are not very clear. Anemia, iron, and vitamin deficiencies, disturbance in peripheral and central nervous system (CNS) functioning and musculoskeletal abnormalities have all been proposed. It is likely that alteration of dopamine activity in the nervous system plays a role (42-43).

Correction of anemia by treatment with erythropoietin has been associated with reduction in the frequency of PLMD, improvement in sleep quality and day time alertness (44).Iron deficiency probably plays a dual role in that it causes anemia and is also a co-factor in the metabolism of dopamine in the brain. Treatment with intravenous iron is associated with a significant improvement in RLS and PLMD(45).Peripheral neuropathy, secondary to uremia or the underlying cause of renal disease such as diabetes may also predispose to develop RLS and or PLMD. Data regarding the clinical and laboratory correlation of RLS and PLMD is inconsistent. Higher predialysis urea and creatinine levels have been associated with increase RLS complaints in one study (1) but no relationship was detected in others (36, 41). Higher intact parathyroid hormone(PTH) levels has been found in dialysis patients with PLMD vs. those without the disorder(46), but lower levels have been noted in uremic patient with RLS in comparison without symptoms(47).
