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Periodic Limb Movements in a Comatose Patient

Case Report

Aires, Ana*; Rocha, Helena; Rego, Ricardo

Journal of Clinical Neurophysiology: July 2019 - Volume 36 - Issue 4 - p 316–318
doi: 10.1097/WNP.0000000000000540
Case Report
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Summary: Periodic limb movements (PLMs) may occur as a primary condition or be associated with other pathologies, such as sleep disorders. However, PLMs have not been described in comatose patients. We report the case of a 66-year-old man, with no history of sleep disorders, who presented PLMs during coma caused by an extensive right hemispheric abscess inducing midline shift. These movements were further characterized by video and electromyographic recordings, which displayed bilateral periodic bursts of the tibialis anterior muscles, occurring every 7 to 15 seconds, with no concomitant electroencephalographic correlate. After a long period of hospitalization, the patient eventually regained consciousness and PLMs seem to persist, only in sleep. To the best of our knowledge, this is the first report showing that PLMs may be observed in a setting where the networks supporting consciousness are lost, namely in a coma of structural etiology.

*Department of Neurology, Centro Hospitalar São João, Porto, Portugal; and

Department of Neurophysiology, Centro Hospitalar São João, Porto, Portugal.

Address correspondence and reprint requests to Ana Aires, MD, Department of Neurology, Centro Hospitalar São João, Porto, Lisboa, Portugal; e-mail: ana.aires.mail@gmail.com.

The authors have no funding or conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.clinicalneurophys.com).

Periodic limb movements (PLMs) are repetitive, often stereotyped, involuntary flexor-withdrawal–like movements that usually occur in non–rapid eye movement sleep (PLM in sleep: PLMS). The diagnosis is made during polysomnography, requiring the electromyographic (EMG) detection of four or more consecutive EMG bursts lasting 0, 5 to 10 seconds, recurring at 5- to 90-second intervals.1,2

The pathogenesis of PLMS has not been fully elucidated yet. Research suggests that there is neuronal hyperexcitability, namely in the brainstem and spinal cord, pointing to a suprasegmental disinhibition. In addition, in EEG, no cortical potential is seen preceding these movements. Some authors also advocate that the subcortical reticular system may be involved in PLMS generation as well as the dopaminergic system.

Periodic limb movement may occur as a primary condition or may be associated with sleep disorders such as restless leg syndrome, narcolepsy, rapid eye movement sleep behavior disorder, and obstructive sleep apnea. Periodic limb movements have also been described in other neurologic conditions including stroke, Parkinson disease, atypical parkinsonian syndromes, and spinocerebellar ataxias. Periodic limb movement can also be induced or worsen with certain medications, such as antidepressants, antihistamines, and antipsychotics.3,4

Although typically observed in the lower limbs during non–rapid eye movement sleep, PLM less commonly involves the upper limbs and may also occur in awake patients.5

Periodic limb movements have been described in brain dead patients6,7 but not in comatose patients who ultimately survived. We report a case of PLM in a patient in coma, lacking a history of previous sleep disorder or other conditions usually known associated with these movements.

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CASE REPORT

The patient was a 66-year-old man admitted after a fall in the context of acute alcohol intoxication. Prior medical history was relevant for chronic alcoholism; he had no history of sleep disorders. He was awake and oriented upon admission, but shortly after had depression of consciousness (Glasgow Coma Scale score of 10) and developed right mydriasis. Brain CT revealed a large (2 cm) right hemispheric subdural hematoma, bilateral frontotemporal small contusions, and several cranial fractures. He was sedated, intubated, and submitted to emergent evacuation of the hematoma. One week postoperatively, his clinical state was complicated by an abscess involving the right frontobasal regions, basal ganglia, and insula, with further midline shift, requiring repeated surgical drainage. Periodic limb movements were first observed 1 month after admission. Sedation had been suspended 2 days before, but he remained intubated and with pressure-assisted ventilation. He was in a coma, with asymmetric motor response to painful stimulation (decerebration on the left and decortication on the right), with bilateral pyramidal signs. His pupils were isocoric and reactive to light, and oculocephalic reflexes were present. At this time, periodic involuntary movements were observed, characterized by rhythmic extension of the hallux, dorsiflexion of the ankle, and flexion of the knee and hip (Fig. 1, Video, http://links.lww.com/JCNP/A49). These episodes affected both legs, at intervals of approximately 7 to 15 seconds, either synchronously or asynchronously, regardless of outside stimuli. The ongoing medications (levetiracetam 500 mg bid, topiramate 50 mg bid, meropenem, captopril, and amlodipine) did not include known PLM precipitants.

FIG. 1

FIG. 1

Laboratory examination (blood count, electrolytes, liver and renal function, thyroid hormones, and ferritin levels) was normal, except for moderate normocytic and normochromic anemia and an elevated C-reactive protein of 18.7 mg/L (normal: <3 mg/L). Cerebrospinal fluid showed a pleocytosis of 412/μL (62.9% polymorphonuclear cells), high protein concentration, normal glucose, and increased lactate levels; bacteriological examination was negative. The EEG revealed slow and disorganized background activity, with dominant delta activity, without epileptiform discharges. Electromyography of tibialis anterior muscles revealed periodic 4- to 5-second bursts, with no concomitant electroencephalographic correlate (Fig. 2). The patient was subsequently submitted to two additional abscess drainages and continued large spectrum antibiotherapy. He was discharged 5 months after admission with substantial neurological recovery. When evaluated at the outpatient clinic, 6 months later, his wife described persisting leg movements during sleep that he had never had before admission. At this time, he was fully conscious, disoriented in time and space, with marked apathy and loss of language fluency. His treatment included levetiracetam, baclofen, mirtazapine, trazodone, and melperone. Ropinirole was then started with increasing doses up to 2 mg/day. Ensuing clinical response is uncertain, since the patient currently sleeps unaccompanied and a subsequent sleep polysomnography, which showed an increased apnea/hypopnea index (51.4/hour) and periods of Cheyne–Stokes breathing, unfortunately did not include EMG recording of leg muscles.

FIG. 2

FIG. 2

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DISCUSSION

We describe PLM in a comatose patient, with video-EEG-EMG documentation. The primary etiology of coma was a supratentorial abscess with secondary compression of diencephalic and brainstem structures.

In our case, no other pathologies associated with PLM were previously identified. Two years after hospitalization, the patient was diagnosed severe sleep obstructive apnea. We believe that PLMs were not related to this disorder because PLM emerged in temporal relation to a brain insult, and at the time they were observed, hypothetical obstructive apnea was nullified by invasive mechanical pressure-assisted ventilation. A Cheyne–Stokes respiration was also identified in polysomnography. When PLMs were registered during hospital stay, respiratory monitoring did not show abnormalities consistent with Cheyne–Stokes respiration, which makes this mechanism less likely to PLM generation.

Interestingly, the interperiod between leg movements in our patient was well within the accepted criteria for PLM but shorter than usually observed in restless leg syndrome or “spontaneous” PLMS (7–15 seconds on our patient; 20–40 seconds on typical restless leg syndrome cases). One of two cases of PLMS reported by Kim et al.,8 where the putative causative lesion was a small infarct in the mid-pons, also had a relatively short interperiod interval (15–25 seconds). Further reports on these rarer cases may help clarify whether a correlation exists between a presumed structural etiology and the temporal profile of PLM.

Ropinirole was instituted to improve PLM; however, as referred, clinical response is uncertain, precluding further attempts to increase the dose. On the other hand, mirtazapine, despite being a potential PLM aggravating factor, was maintained because it clearly ameliorated the patient's troublesome insomnia.

From a pathophysiologic point of view, much is unknown regarding PLM. They resemble spinal cord flexor reflexes and seem to result from a failure of corticosubcortical networks to inhibit the spinal sensoriomotor apparatus.9 In the spinal cord, these structures would be located in lumbosacral segments and one hypothesis is that pathological brainstem disinhibition could activate a lumbosacral generator, resulting in PLM. Observations that PLM can be seen unilaterally after cerebral infarction reinforces this point of view.10,11 Our patient also experienced spontaneous, repetitive, and periodic leg movements during coma that only began after an extensive corticosubcortical lesion capable to induce a comatose state. This lesion involved frontobasal areas, basal ganglia, and insula, and also compressed the brainstem, probably disrupting the regulation of subcortical structures on spinal sensorimotor functioning. Previous reports have shown that PLM may be present in brain death.6,7 Our case highlights that they may also be present in coma with favorable clinical evolution.

On the other hand, beside the referred central nervous generators, it is assumed that subcortical reticular system participates in the production of PLMs because it modulates processes that also have the periodicity observed in those movements (respiration, for example).12 In addition, it is probably responsible for arousals during sleep that may follow a cyclic alternating pattern in opposite to phases where a noncyclic alternating pattern exists.13 Periodic limb movements usually occur during the cyclic alternating pattern. In our case, the reticular system could be intact, so it could also be a generator of PLM.

Previous literature also points out that underactivity of dopaminergic system is said to be pathogenic in PLM. Studies where dopaminergic diencephalospinal neurons of the hypothalamic A11 nuclei of rats were destroyed, the number of PLM during dark was increased.14 In humans, previous case reports proved efficacy of levodopa and dopamine agonists in reducing PLM.10,11 Therefore, we can hypothesize that extensive brain lesions in our patient might modulate the dopaminergic pathway, thereby inducing PLM.

This is the first publication, to the best of our knowledge, to describe PLM in a patient in coma of structural etiology, indicating that this condition can be observed in cases where the networks supporting consciousness are lost.

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REFERENCES

1. Overeem S, Reading P. Sleep disorders in neurology: A practical approach. Hoboken, NJ: Wiley, 2010.
2. American Academy of Sleep Medicine. International classification of sleep disorders. Darien, IL: American Academy of Sleep Medicine, 2014.
3. Cuellar NG. The effects of periodic limb movements in sleep (PLMS) on cardiovascular disease. Heart Lung 2013;42:353–360.
4. Vetrugno R, D'Angelo R, Montagna P. Periodic limb movements in sleep and periodic limb movement disorder. Neurol Sci 2007;28(suppl 1):S9–S14.
5. Alessandria M, Provini F. Periodic limb movements during sleep: a new sleep-related cardiovascular risk factor? Front Neurol 2013;4:116.
6. Jung KY, Han SG, Lee KH, Chung CS. Repetitive leg movements mimicking periodic leg movement during sleep in a brain-dead patient. Eur J Neurol 2006;13:e3–e4.
7. Han SG, Kim GM, Lee KH, Chung CS, Jung KY. Reflex movements in patients with brain death: a prospective study in a tertiary medical center. J Korean Med Sci 2006;21:588–590.
8. Kim JS, Lee SB, Park SK, Han SR, Kim YI, Lee KS. Periodic limb movement during sleep developed after pontine lesion. Mov Disord 2003;18:1403–1405.
9. Rye DB, Trotti LM. Restless legs syndrome and periodic leg movements of sleep. Neurol Clin 2012;30:1137–1166.
10. Kang SY, Sohn YH, Lee IK, Kim JS. Unilateral periodic limb movement in sleep after supratentorial cerebral infarction. Parkinsonism Relat Disord 2004;10:429–431.
11. Woo HG, Lee D, Hwang KJ, Ahn TB. Post-stroke restless leg syndrome and periodic limb movements in sleep. Acta Neurol Scand 2017;135:204–210.
12. Chen Z, Eldridge FL, Wagner PG. Respiratory-associated thalamic activity is related to level of respiratory drive. Respir Physiol 1992;90:99–113.
13. Parrino L, Boselli M, Buccino GP, Spaggiari MC, Di Giovanni G, Terzano MG. The cyclic alternating pattern plays a gate-control on periodic limb movements during non-rapid eye movement sleep. J Clin Neurophysiol 1996;13:314–323.
14. Lopes C, Esteves AM, Frussa-Filho R, Tufik S, de Mello MT. Evaluation of periodic limb movements in a putative animal model of restless leg syndrome. Mov Disord 2012;27:413–420.
Keywords:

Periodic limb movements; Coma; EEG

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