periodic limb movement disorder ( plmd ) is diagnosed when there are periodic limb movements during sleep ( plms ) exceeding norms for age , clinical sleep disturbance , and the absence of another primary sleep disorder or reason for the plms .
pathological periodic limb movement index ( plmi ) is defined as >  15  movements / h in adults .
periodic limb movement disorder is rarer than restless legs syndrome ( rls ) , which is characterized by the sensory motor symptoms frequently associated with plms , usually occurring at night and leading to disrupted sleep and daytime fatigue as in neuromuscular disorders .
several medications are known to induce and/or to worsen plmd ( i.e. , antidepressants , antihistamines , and antipsychotics ) .
although alternative rls / plmd treatments include antiepileptic drugs ( aeds ) , in contrast , topiramate ( tpm)-induced rls also associated with plms was described in four patients affected by epilepsy , .
we report a case of tpm - induced plmd in a patient affected by cryptogenic temporal lobe epilepsy lacking a history of previous sleep disorders .
a 34-year - old male affected by cryptogenic temporal lobe epilepsy previously treated with carbamazepine ( up to 1200  mg per day ) manifested monthly complex partial seizures .
topiramate slowly titrated up to 250  mg per day induced seizure freedom and , afterward , carbamazepine was discontinued .
concurrently , he complained of insomnia , nonrestorative sleep , and daytime sleepiness ( epworth sleepiness scale ( ess ) score : 16 ) .
in addition , his wife reported the appearance of frequent nocturnal leg movements that were never previously observed .
serum examination ( blood count , electrolytes , liver and renal function , thyroid hormones , and iron and ferritin levels ) was unremarkable .
therefore , our patient underwent a full polysomnography ( psg ) that showed a severe plmd ( plmi : 62.7/h ) associated with high plm arousal index ( plmai : 11.9/h ) ; low sleep efficiency ; high sleep latency , wakefulness after sleep onset , and number of awakenings ; high percentage of light sleep ( n2 ) ; and low percentage of slow - wave sleep ( n3 ) ( see table  1 ) .
periodic limb movements during sleep were strictly associated with periodic electroencephalographic arousals and cyclic alternating pattern ( cap ) . in particular ,
cap oscillations were triggered by plm with higher presence of cap subtypes a2 and a3 ( see fig .  1 ) .
these cap subtypes represent an arousal phenomenon that likely leads to clinical correlates of disturbed sleep .
therefore , because of the progressive impairment of insomnia and daytime dysfunction , tpm was slowly discontinued and switched to valproate up to 900  mg per day . during tpm
discontinuation and after complete withdrawal , the patient underwent full psg ( tpm : 50  mg per day ) . periodic limb movement index and
periodic limb movement arousal index showed a significant improvement and , after tpm discontinuation , reached a normal value ( plmi  <  15/h ) .
in addition , the cap rate exhibited a slight reduction , an increase of cap phase a1 and a parallel reduction of phases a2 and a3 .
all psg data are summarized in table  1 . in order to evaluate the association between tpm and plmd ,
the naranjo probability scale   documented a probable association ( naranjo score : 8/13 ) between plmd and tpm intake .
this is the first publication , to our knowledge , to describe tpm - induced plmd in a patient affected by cryptogenic temporal lobe epilepsy previously not complaining of sleep disorders .
although there is a high night - to - night variability of plmi in plmd / rls that may influence our results , this issue is still controversial , and the nocturnal pattern of plm occurrence was highly reliable across nights , suggesting that a single - night study may be sufficiently sensitive to confirm diagnosis and associated sleep disturbances .
therefore , we can state that plmd was probably induced by tpm in our patient .
in addition , rls and plmd pathophysiology is highly debated ; a common central dysregulation of dopaminergic system seems to be implicated .
although such aeds may be effective treatments for rls and plmd , tpm - induced rls was previously described in a few cases  , .
topiramate enhances gaba function and inhibits ampa and kainate glutamate pathways , inducing an extracellular modulation of dopamine release in the mesocorticolimbic dopamine system .
these experimental lines of evidence are confirmed by its efficacy against alcohol , nicotine , and cocaine addictions , .
therefore , we can hypothesize that tpm may modulate the dopaminergic pathway , thereby inducing plmd in subjects with specific individual susceptibility . on the other hand ,
high levels of eeg arousals and/or cap sequences prior to leg movements confirm the presence of sleep impairment in these patients , .
periodic limb movements are short movements that can be entrained by central pattern generators in reciprocal oscillatory coupling .
specifically , cap phases a2 and a3 that represent arousal phenomena are more probably associated with disturbed sleep   as also demonstrated polygraphically in our patient ( fig .  1 ) .
the patients are typically not aware of these limb movements , but quality of sleep may be compromised , and the bed partners might recognize plms . even though the literature failed to document a clear correlation between plms severity and sleep disruption , haba - rubio et al .   found a correlation between plms and tiredness , sleep efficiency , and psychological well - being .
periodic limb movement disorder , insomnia , and diurnal symptoms promptly recovered after drug discontinuation in our patient suggesting a probable association with tpm .
we are aware that , regarding the mutual interactions between sleep and epilepsy , not only sleep deprivation and daytime sleepiness but also abnormal sleep per se represent well - known potential triggers for seizures and are themselves influenced by epilepsy in a sort of reciprocal effect .
notwithstanding , comorbidities and pharmacological treatment are other commonly accepted major factors that influence this interplay .
therefore , an accurate clinical history and psg study in selected cases could be useful in order to recognize potential drug - induced sleep disorders .
on behalf of all authors , the corresponding author states that there is no conflict of interest .
 periodic limb movement disorder ( plmd ) is characterized by pathological periodic limb movements during sleep , insomnia and/or diurnal sleepiness , and the absence of another primary sleep disorder . 
 we report a patient with complex partial seizures who developed plmd while taking topiramate ( tpm ) . 
 he had no evidence of metabolic and/or other conditions inducing plmd . 
 he also had fragmented sleep and disruptive plms on polysomnography , and plms subsided with change of antiepileptic drug . 
 topiramate may modulate the dopaminergic pathway by inhibition of glutamate release , thereby inducing plmd as observed in our patient . 
 although a single case does not allow any generalization , plmd should be considered in patients complaining of insomnia and treated with tpm . 
Introduction
Case report
Discussion
Conflict of interests