Unilateral Poststroke Periodic Limb Movements: A Case Series.

Periodic limb movements (PLM) and restless leg syndrome (RLS) are involuntary common sleep-related movements which often hamper sleep onset; they are mostly idiopathic and bilateral but are seldom described secondary after a stroke. These cases are rare, often unilateral, and because of the usually transitory duration of symptoms, often under-recognized. When a treatment is required, it can be tricky and the drug choice not foregone. We report 2 patients with unilateral poststroke PLM with similar clinical pictures but different symptoms, therapy, and outcome. The first is a long-lasting unilateral PLM video case with chronic vascular lesions leading to insomnia even if with no urgence or any subjective symptoms as in RLS but well responding only to a definite RLS treatment. The second case is an acute, short-duration self-limiting PLM with positive brain MRI lesion imaging. Our cases suggest that unilateral poststroke PLM even if distinct in subjective and radiological features from secondary RLS can sometimes have a definite and effective dopaminergic treatment if long-lasting. Putative mechanism of chronic case 1 PLM could be due to a further stroke sparing sensory pathways and making the patient unaware of subjective RLS-like symptoms.

Introduction

Periodic limb movement (PLM) during sleep is a rhythmic lower limbs movement beginning with an extension of the big toe and dorsiflexion of the ankle followed by a flexion of knee and hip [1]. PLMs were first described in restless leg syndrome (RLS) but occur also in many other sleep disorders as narcolepsy, obstructive sleep apnea syndrome, insomnia, and hypersomnia and are sometimes also reported after a stroke. RLS is a sleep-related disorder with patient subjective discomfort associated with dysesthesia when patients are at rest and urge to move lower limbs to do better. Prevalence of RLS is 5–10% making it the most common among movement disorders [1]. Secondary RLS has many causes, such as iron deficiency, uremia, drug effects (tricyclic or SSRI antidepressants, lithium carbonate, dopamine D2 receptor blockers, or centrally active antihistamines), and alcohol-related effects (both neuropathies and myelopathies). While RLS is more prevalent in women than in men, many previous reports have shown that PLMs are more frequent in men than in women. Acute PLM onset after a stroke (ps-PLM) is occasionally reported [2]. It appears in the contralateral limb after a lacunar lesion in the paramedian portion of the pons and sometimes bilateral PLMs are also described [3], but chronic long-lasting unilateral ps-PLM has not been previously described. Finally, isolated ps-PLMs must be differentiated from bilateral secondary vascular RLS during sleep that are also seldom described [4, 5] because these two conditions have different pathogenetic mechanisms and effective therapies but can share common symptoms. Here, we present our findings in two unilateral ps-PLMs, chronic and long-lasting for 6 months in the former patient with 2 home video recordings and acute and transient in the latter case, with a MRI diffusion-weighted positive image, and we show the different follow-up, outcome, and effective therapies between the two. PLM interval was 30 s in both cases.

Case Series

First Case Report

A 79-year-old man suffered from hypertensive intraparenchymal cerebral hemorrhage in 2013 with a subsequent spastic left hemiparesis. Six years later, in April 2019, he suffered from involuntary movements in the paretic limb making sleep difficult. This movement was stereotyped, always starting with a dorsal extension of the big toe and the foot and rapidly extending to the leg and thigh, lifted and flexed (see online suppl. Video 1; for all online suppl. material, see www.karger.com/doi/10.1159/000522334). Its intermovement interval was constant about 20–25 s all-night long while lying down before sleeping, making falling asleep not possible due to continuous awakenings after this pattern of movement but surprisingly with no subjective discomfort by this nondemented patient except insomnia; this movement was absent during the day and even during his nap after lunch. Online supplementary Video 2 shows both legs without an evident contralateral tibialis anterior activation. Brain MRI was negative for recent ischemic lesions, but it was performed 6 months after the onset of symptoms and showed a parenchymal gliosis in the white matter of the frontal, parietal peritrigonal, and occipital regions; on diffusion-weighted imaging, no increased signal was detectable. On MRI T2-weighted sequences, a hypointensity of the right basal ganglia region, posterior talamic nuclei, and internal capsule posterior arm was present, as a past hemorrhagic lesion marker. The right corticospinal tract Wallerian degeneration was evident with a right lateral ventricle dilatation and Sylvian fissure and frontoparietal convexity subarachnoid spaces enlargement. A comprehensive hematological assessment with serum iron level was normal. Subsequently, his ongoing therapy with baclofen was increased to 12.5 mg tid and pregabalin 50 mg die was added to delorazepam 0.5 mg but with no benefit. Afterward, assuming a drug-related mechanism his long-standing antidepressant drug (paroxetine 20 mg) and baclofen were withdrawn and pregabalin was reduced to 25 mg at night increasing delorazepam to 1.5 mg. Unfortunately, no benefit was observed after these therapy changes and his paretic limb spasticity did increase leading to a sleep deprivation-related marked daily somnolence. As a consequence, baclofen was up-titrated to 25 mg half a pill tid and delorazepam reduced to 0.5 mg again and finally, Rotigotine 2 mg was introduced at night. In the following days, nocturnal clinical picture improved abruptly and PLMs disappeared. At 12-month follow-up, the patient is still asymptomatic.

Second Case Report

A 89-year-old man affected by hypertension was admitted to ER in December 2019 with acute dysarthria, dysphagia, and left facio-brachio-crural hemiplegia not suitable to intravenous rt-PA for delayed arrival and CT scan unremarkable. On the following day, a repetitive stereotyped movement with a dorsal extension of the big toe and the foot in the paretic limb appeared. Its intermovement interval was every 30 s, both during sleep and awake. Patient was always unaware of this PLM that lasted about 48 h and disappeared spontaneously making any treatment unnecessary. Brain MRI diffusion-weighted imaging, performed 6 days from stroke onset when the patient was PLM-free, showed a recent wide right paramedian and lateral pontine lesion in the territory of the basilar perforating arteries accompanying a global parenchymal gliosis (see MRI figures) (Fig. 1, 2). Blood and iron values were normal. Unfortunately, the patient deteriorated for respiratory failure and died a few days later.

Fig. 1

Diffusion-weighted MRI images showing hyperintensity of the right lateral pons due to a recent ischemic lesion in case #2.

Fig. 2

Diffusion-weighted MRI images showing hyperintensity of the right paramedian pons due to a recent ischemic lesion in case #2.

Conclusions

In these two cases, any other cause of secondary PLM apart from vascular and also the possibility that PLM existed before stroke were ruled out. Patients or caregivers never reported such involuntary movements and, especially patient #1, never had PLMs-related insomnia symptoms. Accordingly, no nocturnal polysomnography or polygraphy was performed before our observation. Ps-PLMs are described to decrease after hemispheric stroke [6], while they can persist after a spinal ischemia. Conversely, RLS after stroke is also described and is found mainly after pontine, thalamic, basal ganglia, or corona radiata strokes but usually it is bilateral and begins about 1 week after the stroke, accompanied by PLM in sleep and leading to insomnia [7]. Ps-PLMs are uncommon features among poststroke symptoms and, differently from idiopathic PLM and RLS, are never bilateral. The literature contains about 30 cases of ps-RLS or ps-PLMs, and a causative lesion was most frequently located in the pons [8]. Site lesions in both the pontine base and tegmentum (together) were associated with unilateral ps-PLMs, whereas lesions in the corona radiata and adjacent basal ganglia (nucleus pallidus) were associated with bilateral RLS. Lesions confined to the corona radiata only result in either unilateral or bilateral RLS. These 2 patients we have recently observed showed very similar unilateral ps-PLM but had quite distinct clinical symptoms. Paramedian and lateral pons lesions are involved in the development of secondary PLM in the contralateral limb [3], as confirmed by MRI in our second patient, and its brief lasting has been already recently described [9]. In the first patient, conversely, his PLM gradually increased to chronic PLM and his delayed admission to MRI neither evident any recent detectable site of lesion nor evident new vascular lesions along the motor pathway even if a further ischemic lesion was suspected. Notably symptoms were stereotyped and present only in the evening and during the night as in RLS, making sleep impossible but with no other subjective symptoms (urge to move, discomfort, paresthesia) unlike in RLS and always strictly unilateral (see online suppl. Video) as in confirmed ps-PLMs. Falling asleep was highly difficult for the patient. He tried to fall asleep in an almost seated position but with no success. Since PLMs were very long-lasting (6 months) any other cause of unilateral PLM was excluded, also the chance of a further causative neurodegenerative syndrome [10]. Interestingly, drug choices as in PLM (benzodiazepines, baclofen, pregabalin) were ineffective in this patient and only a definite RLS therapy, even if at very low doses (rotigotine 2 mg) was finally successful. We suppose that a further new ischemic lesion has happened along his motor pathway sparing sensory subcortical structures and without any subjective paresthesia, but we have no such lesion imaging confirmation because of the late patient access to neurologic observation, making any positive MRI diffusion imaging unremarkable 6 months later. A lesion in the pathway projecting from the thalamic parafascicular nucleus to intermediolateral column of spinal cord could be implicated in the pathogenesis of these ps-PLMs. Its location close to the hypothalamic suprachiasmatic nucleus regulating the circadian clock could explain patient nocturnal symptoms [11]. The patient always did deny any RLS symptoms but clearly improved after a definite dopaminergic therapy [12]. Patient #2 did not report any symptoms either. Moreover, he was completely unaware of his PLMs, which were present also when he was awake. This case series has the bias that this is a single-center report and PLMs were not recorded by polygraphy but only by home video recordings in case 1. It was due to the prolonged time of onset in case 1 with a severe insomnia requesting a prompt treatment to relieve insomnia and the very short duration of movements before death in case 2. Conversely, these video recordings and MRI images support their phenomenology and confirm the sites of lesion which can lead to ps-PLMs, and we believe it could be of interest to medical staff dealing with stroke.

Statement of Ethics

This retrospective review of patients' data did not require ethical approval in accordance with local guidelines. Written informed consent was obtained from the patient #1 and from his next of kin for #2 for publication of this case report and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

No funding was received for this study.

Author Contributions

Author roles: (1) Research project: A. Conception, B. Organization, C. Execution; (2) Manuscript: A. Writing of the first draft, B. Review, and Critique. Author MCM: 1ABC, 2AB. Author EC: 2BC. Author IL: 2B. Author CM: 2B. Author CL: 1A, 2BC.

Data Availability Statement

All data are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.

Supplementary data

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Supplemental Video

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Supplemental Video

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