Restless leg syndrome and Parkinson’s disease correlation in backdrop of iron deficiency anemia

Summary

Restless leg syndrome and Parkinson’s disease are both common neurological disorders. There has been much debate over whether an etiological link between these two diseases exists and whether they share a common pathophysiology. (1)

This blog tries to explain the link between the two neurological conditions in correlation with iron deficiency anemia. This article attempts to simplify the viewpoint with support of various reviews and studies.

Introduction

Restless leg syndrome is a movement disorder in which patients present with urge of moving their limbs frequently, accompanied by burning, twitching or pain in the limbs especially lower limbs. Onset of symptoms is frequently during period of rest or inactivity and an exacerbation of unpleasant sensations is reported in those situations where immobility is forced such as driving, flying long distance, watching movies in theater and attending business meetings. Restless leg syndrome has a clear circadian trend with peaks in the evening or at night that can severely compromise nocturnal sleep quality and quantity, due to which patients also present with complain of difficulty falling asleep or frequent nocturnal awakenings that disrupt sleep continuity. Therefore, during day time patients experience irritability, fatigue and drowsiness with cognitive impairments. (2)

Causes

Restless leg syndrome can be idiopathic but can also occur in comorbid patients. The secondary form is disconnected in several studies reporting its relationship with polyneuropathy, deficiency, anemia, multiple sclerosis, hypertension, cardiovascular disease. However, in recent years, a growing body of literature investigated the association between restless leg syndrome and Parkinson’s disease. (3) According to the study (3), we can rely on the fact that disruption in the brain, iron trafficking leads to disturbance in striatal dopamine neurotransmitter.

Importance of this blog

Various studies have documented the effects of iron deficiency and its significance in Parkinson’s disease and restless leg syndrome. Despite this, many people are not aware about the staggering effects of this micronutrient deficiency. Hence, bringing this topic on a public platform helps in spreading awareness and can be tackled at primary level of prevention. To support the statement, according to a study (4), the current consensus guidelines put forth by restless leg syndrome foundation medical advisory board recommend iron replacement therapy for people with low ferritin level (less than 20 micrograms).

According to another systematic review (5) iron probably improves restlessness in people with restless leg syndrome.

In yet another nested control study (6), association between anemia and Parkinson’s disease is demonstrated. The association could be explained by impaired brain oxygenation, dysregulation of iron homeostasis and oxidative stress.

Conclusion

There is pathological evidence of dopamine dysfunction in Parkinson’s disease and restless leg syndrome. Post-mortem studies in Parkinson’s disease demonstrate loss of nigral neurons resulting in striatal dopamine deficiency, with differing morphological lesions patterns, according to the clinical subtype of Parkinson disease. The cell loss in ventrolateral part of substantia nigra pars compacta projecting to dorsal putamen is more prominent in akinetic rigid type, whereas tremor dominant Parkinson’s disease shows prominent medial substantia nigra pars compacta cell loss.

An autopsy of 8 patients with primary restless leg syndrome showed that there was a significant decrease in dopamine 2 receptors in putamen compared to the neurologically normal control group. This evidence that the nigrostriatal dopaminergic system is affected in both restless leg syndrome and Parkinson’s disease might provide a stronger argument for an etiologic link between the two.

Various clinical association studies are conducted among which the study (7-8) examining the association between restless leg syndrome and Parkinson’s disease, found that in a study of 126 Parkinson’s disease patients and 128 healthy age and sex matched controls in India, restless leg syndrome was found to be present in 10 patients and 1 control.

Certain similarities and differences exist between restless leg syndrome and Parkinson’s disease. Dopaminergic disturbances appear to underpin both diseases suggesting that there may be some overlap in pathophysiology.

Iron was significantly decreased in substantia nigra and somewhat less significantly in the putamen, both in proportion to restless leg syndrome severity suggesting that brain iron insufficiency may occur in restless leg syndrome patients. (1)

Reference

1. Tasneem Peeraully and Eng-King Tan, “ Linking restless legs syndrome with Parkinson’s disease- clinical, imaging and genetic evidence.

2. Lungi-Ferini-Strambi, Guilia Carli, Francesca Casoni, Andrea Galbiati. Restless legs syndrome and parkinson disease- a causal relationship between the two disorders.

3. Christopher J Earley, James Connor, Diego Garcia Borreguero, Peter Jenner, John Winkelman, Phyllis C Zee, Richard Allen. Altered brain iron homeostasis and dopaminergic function in restless leg syndrome.

4. Silber MH, Becker PM, Earley C, Gracia-Borreguero D, Ondo WG. Willis-Ekbom disease foundation revised consensus statement on the management of restless leg syndrome.

5. Lynn M Trotti, Lorne A Becker, Iron for treatment of restless leg syndrome.

6. Ji Hee Kim, Jae Keun Oh, Jee Hye Wee, Chan Yang Min, Dae Myoung Yoo and Hyo Geun Choi, Association between anemia and parkinson disease: a nested case control study using a national health screening cohort.

7. Nomura T, Inoue Y, Miyake M, Yaswik, Nakashima K, Prevalence and clinical characteristics of restless leg syndrome in Japanese patients with parkinson disease.

8. Loo HV, Tan EK, Case control study of restless leg syndrome and quality of sleep in parkinson disease.

Writer: Dhruv Barai

Editor: Uma Arun Unni