Stroke-Related Restless Legs Syndrome an ‘Emerging Entity’

More data support the concept of stroke-related restless legs syndrome as an “emerging entity,” investigators report in a new study.

New research has identified the lenticulostriate and ventral brainstem as the main regions implicated in stroke-related restless leg syndrome (s-RLS). Researchers also observed dopaminergic dysfunction in patients with sRLS.

“Clinicians should be aware of sRLS characteristics for appropriate diagnosis,” especially since “efficient treatments are available to relieve patients’ symptoms,” write the authors, led by Elisabeth Ruppert, MD, Department of Neurology, Sleep, and Electrophysiology Clinic, University Hospital of Strasbourg, France.

The study was published online in the European Journal of Neurology.

A common neurologic condition, RLS is characterized by an irresistible urge to move the lower limbs, they note. Symptoms are improved by movement and worsened at rest and in the evening.

Research shows RLS decreases quality of life, and severe forms can be debilitating and increase mortality.

The authors characterize what they call “the emerging entity of sRLS” in a series of 16 patients — eight men and eight women aged 41 to 81 years. These patients were hospitalized at the Stroke Unit of the University Hospital of Strasbourg and diagnosed with either de novo RLS (12 patients) or clear exacerbation of past RLS.

As RLS preceded stroke symptoms in some patients, the authors believe the term “stroke-related” RLS is more accurate than “post-stroke” RLS.

None of the participants had any condition other than sRLS that could explain their symptoms. None had a family history of RLS, took medication implicated in RLS pathophysiology, or had clinical symptoms of neuropathy.

Brain MRI was performed in all patients within 48 hours of their stroke.

Twelve patients underwent video polysomnography. Results showed significant periodic limb movements during sleep (PLMS) in eight patients. Moderate or severe obstructive sleep apnea syndrome was identified in eight patients.

A subgroup of 11 patients underwent metabolic brain imaging (positron emission tomography [PET] to determine glucose consumption, single-photon emission CT for dopamine reuptake via dopamine active transporter [DAT], and PET scanning for presynaptic dopaminergic synthesis.)

RLS was bilateral and symmetric in 13 patients, but all patients had a unilateral stroke. Some patients only had a deficit in the upper limb, but no patient complained of restless arms syndrome.

“The question of how mostly bilateral and symmetric RLS symptoms are related to a unilateral stroke involving a leg or even an upper limb is intriguing,” the authors write.

The lenticulostriate area was involved in eight stroke patients; it was left-sided (dominant hemisphere) in six and right-sided (minor hemisphere) in two. Seven patients had a ventral brainstem stroke, affecting the pons in six and the medulla oblongata in one.

“These stroke locations could be predictive factors for sRLS,” they note.

Most patients with lenticulostriate lesions had dopaminergic dysfunction. Researchers found a significant hyperdopaminergic state persisted in six patients with values that were more than twice the standard deviation when compared with a control population of 20 subjects.

The body of the caudate nucleus was the most commonly lesioned structure in those with stroke in the lenticulostriate region. “The exact role of this relay structure receiving a rich dopaminergic innervation remains unclear,” said the authors.

They explained that increased dopamine synthesis in the striatum ipsilateral to the infarct could result from local neural plasticity. “In predisposed patients, stroke in the lenticulostriate area could unbalance a finely tuned neurobiological equilibrium in the striatum and lead to dysfunction in the cortico-striatal-thalamic-cortical circuits.”

But whether the hyperdopaminergic state in lenticulostriate sRLS is an association or the causation is unknown, they said.

In the case of a ventral brainstem stroke, sRLS could occur either as a result of a lesioned descending corticospinal tract, or damaged cortico-pontocerebellar fibers, or because this condition needs both tracts lesioned, the researchers conclude.

“This could impact on the spinal dopamine receptors and unbalance the sensorimotor circuits in the spinal cord, a gateway for the sensory processing of the symptoms.”

The authors have disclosed no relevant financial relationships.

Eur J Neurol. Published online December 9, 2021. Abstract  

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