Journal of Postgraduate Medicine
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Year : 2015  |  Volume : 61  |  Issue : 2  |  Page : 116-119  

Painful legs and moving toes syndrome responsive to pregabalin

FH Rossi1, W Liu1, E Geigel2, S Castaneda1, EM Rossi1, K Schnacky3,  
1 Department of Neurology, Orlando Veteran Affairs Medical Center in Orlando, Orlando, Fl, United States of America
2 Department of Pulmonary, Orlando Veteran Affairs Medical Center in Orlando, Orlando, Fl, United States of America
3 Department of Pharmacy, Orlando Veteran Affairs Medical Center in Orlando, Orlando, Fl, United States of America

Correspondence Address:
F H Rossi
Department of Neurology, Orlando Veteran Affairs Medical Center in Orlando, Orlando, Fl
United States of America


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.

How to cite this article:
Rossi F H, Liu W, Geigel E, Castaneda S, Rossi E M, Schnacky K. Painful legs and moving toes syndrome responsive to pregabalin.J Postgrad Med 2015;61:116-119

How to cite this URL:
Rossi F H, Liu W, Geigel E, Castaneda S, Rossi E M, Schnacky K. Painful legs and moving toes syndrome responsive to pregabalin. J Postgrad Med [serial online] 2015 [cited 2023 Sep 28 ];61:116-119
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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. [1] 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. Pain is commonly refractory to therapies. [2] We report in this paper three cases who favorably responded to pregabalin. The first and third cases showed a sustained positive response to pregabalin. The second case also responded favorably to pregabalin, but the drug had to be discontinued because of side effects.

 Case Reports

Case 1

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. Pain was constant, dull, and affecting his entire right foot. The right foot toes moved up and down involuntarily. These symptoms did not change with rest, walking, or any other activity, nor the time of the day. The patient denied an urge to move his leg or toes. 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. There were no muscle fasciculations, atrophy, or myokymia. Muscle strength and reflexes were normal except for mildly reduced ankle jerks. Light touch, pinprick, vibration, and cold sense were normal with no hyperalgesia, hyperpathia, or allodynia. Nerve conduction studies showed an axonal loss polyneuropathy. 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. Pregabalin was initiated at 150 mg twice daily and was effective in controlling pain. 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.

Case 2

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. His past history was significant for left ankle surgery and hemochromatosis requiring periodic phlebotomies. There was no history of diabetes mellitus. Neurological examination revealed normal mental status, cranial nerves, and coordination. Motor exam showed normal strength, but showed an involuntary non-suppressible flexion and extension movement of his left great toe. Vibratory sensation was decreased at the toes. Reflexes were diminished at the knees and absent at the ankles. Gait was steady and slow with a mild limp caused by chronic left hip pain. He had 2+ leg edema. Electromyogram/nerve conduction study(EMG/NCS) showed a mixed pattern polyneuropathy. Laboratory work-up was unremarkable, except for low ferritin. 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.

Case 3

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 also complained of involuntary toe movements affecting either foot. Symptoms were worse at rest and at night, relieved with activity. He had been taking ropinirole since diagnosed with RLS, which was initially helpful but was unable to tolerate increased doses. He failed trial with Gabapentin. 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. He could briefly suppress the toe movements for a few seconds. Laboratory work-up was unremarkable. Initial EMG/NCS was normal, but a follow up EMG/NCS two-and-half-years later revealed an axonal sensorimotor polyneuropathy. Patient was initiated on pregabalin at 75 mg at bedtime without benefit. Dose was further increased to 75 mg po BID. 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. His restless leg syndrome had also improved.


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. Movements affect toes more than foot with a continual wriggling and writhing motion. [1] The disorder may affect one leg alone, or spread to involve both legs. [1],[2] PLMT is more common in women. 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. [2] The etiology of PLMT remains unknown. PLMT can be idiopathic or associated with several disorders, with peripheral neuropathy, trauma, and radiculopathy among the most common etiologies. [2],[3] [Table 1] shows conditions associated with PLMT.{Table 1}

The diagnosis of PLMT is based on history and physical examination. Complementary studies may reveal additional information, but rarely are necessary. 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. [2],[4] Electroencephalography is normal. [4] 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). [5]

The pathophysiology of PLMT syndrome remains elusive. 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. [4],[6],[7] 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. [1],[2],[3],[4] {Table 2}

There is currently no treatment for PLMT. Many pharmacologic and nonpharmacologic therapies have been applied in 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. [1],[2],[3],[4] Most have had disappointing results and offer no permanent relief.

This article reviews three patients whose pain responded favorably to pregabalin. 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 150mg 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. The mechanism of pregabalin analgesia is not completely understood. 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. [8],[9] Pregabalin is effective in the therapy of different chronic pain disorders such as painful diabetic polyneuropathy, post herpetic neuralgia, and fibromyalgia. [8],[10] The usual therapeutic dose ranges from 150 mg to 600 mg per day. Pregabalin is well tolerated with low incidence of adverse events; drowsiness and dizziness are the most frequent dose-limiting events. [8]

Gabapentin, another GABAergic agent structurally related to pregabalin, has also shown benefit in PLMT. [11],[12] 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. [13] A second case reported benefit in pain and toe movements with combination of baclofen and clonazepam, [14] but the benefit was transient, lasting only eight months. Baclofen and clonazepam are both GABA agonists. Clonazepam affects GABA-A type receptor, whereas baclofen affects GABA-B type receptor. [15] 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. [16]

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. Pain is often intractable to therapy. Pregabalin is probably effective and should be considered for this condition.


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