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painful legs and moving toes ( plmt ) is the descriptive term given to an unusual syndrome first recognized by spillane and colleagues in 1971 .
the main features of this syndrome are involuntary and irregular movements of the toes associated with moderate to severe diffuse pain felt deeply in the foot and leg .
the pathophysiology of this syndrome is poorly understood and there are no current guidelines on its treatment .
the second case also responded favorably to pregabalin , but the drug had to be discontinued because of side effects .
a 64-year - old hispanic male , a former boxer , with a past medical history of diabetes mellitus , early alzheimer 's dementia and spinal stenosis , presented with a seven - month - history of right foot pain and involuntary jerky movements of his toes .
these symptoms did not change with rest , walking , or any other activity , nor the time of the day .
he was on glipizide , lisinopril , hydrochlorothiazide , donepezil , ferrous sulfate , simvastatin , and atenolol .
the neurological examination revealed intermittent , irregular flexion and extension movements of all the toes on the right foot .
light touch , pinprick , vibration , and cold sense were normal with no hyperalgesia , hyperpathia , or allodynia .
laboratory revealed a mild anemia ; otherwise hemoglobin a1c , thyroid stimulating hormone , hepatic enzymes , vitamin b-12 level , lipid panel , and complete blood cell count were normal .
brain mri with and without contrast showed a few non - specific scattered non - enhancing white matter lesions .
lumbar spine mri showed moderate to severe canal stenosis at l2 - 3 , l3 - 4 , and l4 - 5 , but no nerve root compression .
the patient 's baseline pain score was 9/10 that decreased to a 4/10 after addition of pregabalin .
he also reported an improvement in activities of daily living , increased duration of exercise , and quality and duration of uninterrupted sleep .
an increase of pregabalin up to 300 mg twice daily showed a further improvement in quality of life with good tolerance .
however , the movement of the toes persisted despite adequate pain control for six months .
he was subsequently lost to follow up . a 77-year - old white male presented with left heel paresthesias , left great toe pain , and involuntary constant movements of the left great toe , which was worse at night .
he was previously diagnosed with restless leg syndrome , but had failed multiple drug trials including with carbidopa / levodopa , ropinirole , and tramadol .
motor exam showed normal strength , but showed an involuntary non - suppressible flexion and extension movement of his left great toe .
gait was steady and slow with a mild limp caused by chronic left hip pain .
the patient was initiated on pregabalin and titrated to 150 mg orally twice a day . in a
follow up visit one month later , he reported almost complete cessation of great toe movements and paresthesias with significant improvement in pain . however , because of worsening of lower extremity edema , which is a known side effect of this medication , pregabalin dose was reduced and subsequent discontinuation was required . at a later date ,
the patient was re - challenged on a lower dose of pregabalin-50 mg orally twice daily  that helped reduce but not eliminate his toe movements or pain .
further pregabalin dose increases were poorly tolerated with significant exacerbation of leg edema , which resulted in pregabalin discontinuation . a 56-year - old white male presented with inability to sit still with an aching sensation throughout both legs , worse from the feet to the knees with tingling of the soles of the feet .
he was previously diagnosed with restless leg syndrome ( rls ) two years prior to initial neurology visit .
he had been taking ropinirole since diagnosed with rls , which was initially helpful but was unable to tolerate increased doses .
neurological examination was completely normal including mental status , cranial nerves , motor , sensory , coordination , reflexes , and gait .
he was noted to have involuntary toe movements of the second and third toes of both feet , worse on the left .
initial emg / ncs was normal , but a follow up emg / ncs two - and - half - years later revealed an axonal sensorimotor polyneuropathy .
seven months later while on same dose of pregabalin revealed a significant improvement in pain , and almost complete resolution of his toe movements .
a 64-year - old hispanic male , a former boxer , with a past medical history of diabetes mellitus , early alzheimer 's dementia and spinal stenosis , presented with a seven - month - history of right foot pain and involuntary jerky movements of his toes .
these symptoms did not change with rest , walking , or any other activity , nor the time of the day .
he was on glipizide , lisinopril , hydrochlorothiazide , donepezil , ferrous sulfate , simvastatin , and atenolol .
the neurological examination revealed intermittent , irregular flexion and extension movements of all the toes on the right foot .
light touch , pinprick , vibration , and cold sense were normal with no hyperalgesia , hyperpathia , or allodynia .
laboratory revealed a mild anemia ; otherwise hemoglobin a1c , thyroid stimulating hormone , hepatic enzymes , vitamin b-12 level , lipid panel , and complete blood cell count were normal .
brain mri with and without contrast showed a few non - specific scattered non - enhancing white matter lesions .
lumbar spine mri showed moderate to severe canal stenosis at l2 - 3 , l3 - 4 , and l4 - 5 , but no nerve root compression .
the patient 's baseline pain score was 9/10 that decreased to a 4/10 after addition of pregabalin .
he also reported an improvement in activities of daily living , increased duration of exercise , and quality and duration of uninterrupted sleep .
an increase of pregabalin up to 300 mg twice daily showed a further improvement in quality of life with good tolerance .
however , the movement of the toes persisted despite adequate pain control for six months .
a 77-year - old white male presented with left heel paresthesias , left great toe pain , and involuntary constant movements of the left great toe , which was worse at night .
he was previously diagnosed with restless leg syndrome , but had failed multiple drug trials including with carbidopa / levodopa , ropinirole , and tramadol .
motor exam showed normal strength , but showed an involuntary non - suppressible flexion and extension movement of his left great toe .
gait was steady and slow with a mild limp caused by chronic left hip pain .
the patient was initiated on pregabalin and titrated to 150 mg orally twice a day . in a follow up visit
one month later , he reported almost complete cessation of great toe movements and paresthesias with significant improvement in pain . however , because of worsening of lower extremity edema , which is a known side effect of this medication , pregabalin dose was reduced and subsequent discontinuation was required . at a later date ,
the patient was re - challenged on a lower dose of pregabalin-50 mg orally twice daily  that helped reduce but not eliminate his toe movements or pain .
further pregabalin dose increases were poorly tolerated with significant exacerbation of leg edema , which resulted in pregabalin discontinuation .
a 56-year - old white male presented with inability to sit still with an aching sensation throughout both legs , worse from the feet to the knees with tingling of the soles of the feet .
he was previously diagnosed with restless leg syndrome ( rls ) two years prior to initial neurology visit .
he had been taking ropinirole since diagnosed with rls , which was initially helpful but was unable to tolerate increased doses .
neurological examination was completely normal including mental status , cranial nerves , motor , sensory , coordination , reflexes , and gait .
he was noted to have involuntary toe movements of the second and third toes of both feet , worse on the left .
initial emg / ncs was normal , but a follow up emg / ncs two - and - half - years later revealed an axonal sensorimotor polyneuropathy .
a follow up visit seven months later while on same dose of pregabalin revealed a significant improvement in pain , and almost complete resolution of his toe movements .
painful legs and moving toes is a rare syndrome with involuntary and irregular movements of toes and moderate to severe pain in the foot and leg .
the pain is often continuous and throbbing in nature and its intensity may vary from constant discomfort to a living torment .
the presenting age of onset is from second to seventh decade of life , although the mean age of onset is the sixth decade of life .
plmt can be idiopathic or associated with several disorders , with peripheral neuropathy , trauma , and radiculopathy among the most common etiologies .
medical conditions associated with plmt the diagnosis of plmt is based on history and physical examination .
electrodiagnostic tests ( nerve conduction studies and emg ) may show a peripheral neuropathy or root lesions .
emg may show spontaneous repetitive and irregular bursts lasting from 50 milliseconds to 1 second with a frequency of 2 to 200 hz in association with the movement .
polysomnography may shows disruption of the sleep patterns with predominance in light sleep , reduction in slow wave sleep , and fragments of rapid eye movement ( rem ) .
lesions of peripheral nerves and/or central nervous system are possibly implicated in the genesis of spontaneous inappropriate electrical impulses .
posterior nerve roots and afferent nerve fibers lesions generate spontaneous frequent discharges that may lead to reorganization of segmental or suprasegmental efferent motor pathways with pain arising as a central effect and abnormal movement from activation of motor neurons .
the differential diagnosis of plmt includes restless leg syndrome , polyneuropathy , akathisia , and nocturnal leg cramps .
table 2 shows the main similarities and differences between plmt and its most common imitators .
plmt differential diagnosis rls  restless leg syndrome ; epc  epilepsy partialis continua ; pd  parkinson disease there is currently no treatment for plmt .
these include baclofen , benzodiazepines ( diazepam , clonazepam ) , anticonvulsants ( carbamazepine , gabapentin ) , tricyclic antidepressants , beta blockers , corticosteroids , lumbar sympathetic blockade , transcutaneous electrical nerve stimulation with or without vibratory stimulation , and analgesics .
case 1 : the patient responded successfully to pregabalin at doses of 150 mg bid , even better at 300 mg bid , and the effect was sustained for six months .
case 2 : the patient responded to pregabalin ( at a dosage of 150 mg bid ) but developed exacerbation of lower extremity edema prompting reduction and then discontinuation of this medication .
case 3 : the patient responded successfully to pregabalin dose 75 mg bid , which was sustained at seven - month follow up .
pregabalin binds to the alpha 2-delta subunit of voltage - dependent calcium channels in the central nervous system reducing presynaptic end neuronal calcium currents .
this reduces the calcium influx at the nerve terminals and subsequently reduces the release of neurotransmitters ( glutamate , substance p , and noradrenaline ) involved with the ascending neuropathic pain transmission pathway at the level of the dorsal horn neurons .
pregabalin is effective in the therapy of different chronic pain disorders such as painful diabetic polyneuropathy , post herpetic neuralgia , and fibromyalgia .
pregabalin is well tolerated with low incidence of adverse events ; drowsiness and dizziness are the most frequent dose - limiting events .
gabapentin , another gabaergic agent structurally related to pregabalin , has also shown benefit in plmt .
one study showed improvement in pain and involuntary movement with gabapentin at 300 mg three times per day for three months , at which time the dose was doubled to further control pain and movement . in another study ,
partial relief was achieved with gabapentin 200 mg three times daily , with more complete control of pain at 700 mg per day . however , toe movement continued in both studies . combination of gabaergic agents , such baclofen and clonazepam , are potentially effective in plmt syndrome .
a patient who developed plmt after taking the antipsychotic drug molindone was successfully treated with combination of baclofen and clonazepam .
a second case reported benefit in pain and toe movements with combination of baclofen and clonazepam , but the benefit was transient , lasting only eight months .
clonazepam affects gaba - a type receptor , whereas baclofen affects gaba - b type receptor .
chronic use of these drugs can theoretically lead to possible downregulation of gaba receptors with reduced therapeutic value . a gabaergic agent , progabide , used in europe as antiepileptic , showed similar response to clonazepam and baclofen .
progabide is a gaba agonist that has an effect on gaba - a and gaba - b receptors . in summary , we report three patients with plmt syndrome who favorably responded to pregabalin . we recommend pregabalin in the therapy of plmt syndrome , although more studies are necessary to confirm these observations .
painful leg moving toe syndrome is a rare syndrome , poorly understood , presenting with abnormal involuntary movement of the toes and moderate to severe pain of the foot and leg .
report three cases of painful legs and moving toes ( plmt ) syndrome responsive to pregabalin along with a review of its literature . 
 three patients with plmt syndrome improved with pregabalin . 
 the first and third patient reported improvement in pain scores , quality of life , and quality of sleep sustained over time . 
 the second and third patient had near complete remission of toe movements , but pregabalin was discontinued in the second patient due to aggravation of leg edema . 
 plmt is a rare and debilitating disorder characterized by lower limb pain and involuntary toes or feet movements . 
 its pathophysiology remains unknown and its therapy refractory to most drugs , except for pregabalin , as shown in this case series . 
 plmt is a rare and incapacitating syndrome due to the lack of an effective pain therapy . 
 we report three patients with plmt who favorable responded to pregabalin . 
 we propose pregabalin be considered in the management of plmt .