Case series of painful legs and moving toes: Clinical and electrophysiologic observations

We present a retrospective review of cases of painful legs and moving toes (PLMT) syndrome. Out of 4,780 database patients with movement disorders diagnosed at Mayo Clinic Arizona from 1996 to 2006, we identified 14 cases of PLMT and its variants (6 men, 8 women). Ages ranged from 25 to 84 years (mean, 69 years). Movements were bilateral in 12 and unilateral in 2. Pain preceding the movements was most commonly burning; movements consisted of flexion/extension, abduction/adduction, fanning, or clawing of toes, fingers, and sometimes the foot or hand. The most common predisposing factors were neuropathy and radiculopathy. Surface electromyography showed movements suggestive of both chorea and dystonia. Movements were partially suppressible and were diminished but still apparent during light sleep. GABAergic agents were most effective in controlling the pain and the movements. © 2008 Movement Disorder Society     

Painless legs and moving toes in a mother and her daughter.

Painful legs and moving toes (PLMT) is a rare syndrome which is characterised by involuntary movements of the toes and pain in the legs. We report on a mother and her daughter who both presented with involuntary movements of the toes similar to those seen in PLMT but without any associated pain. Neurological examination revealed intermittent 0.3 to 0.5-Hz flexion and extension of the toes and ankles of the right foot in the mother, and of both feet in the daughter. In both patients, the movements appeared during periods of rest that were uncorrelated with the time of day. Diagnostic work-up gave no evidence of radiculopathy or of focal neuropathy. Overnight polysomnography documented that movements of the toes and feet occurred only before sleep onset and during periods of nocturnal awakening or arousals. Because the movements observed in our patients were similar to those seen in patients with PLMT, we diagnosed an abortive form of this syndrome, which already has got the naming "painless legs and moving toes." The occurrence in a mother and her daughter may point to a hereditary component of this disorder.     

Painless legs moving toes in a patient with Wilson's disease.

We describe and present a video of a 20-year-old woman with Wilson's disease (WD) who developed the painless variant of painful legs and moving toes (PLMT) syndrome. The symptoms appeared during a subsequent minor exacerbation of her extrapyramidal symptomatology, only to gradually disappear 3 to 4 months later. We suggest that, in our case, a structural central nervous system lesion caused by WD may have been associated with the development of PLMT.     

Painful leg and moving toes syndrome

Painful leg and moving toes (PLMT) syndrome is a distinct clinical entity and in majority of the patients there are some underlying causes related to spinal cord, cauda equina, or peripheral neuropathy. However, some cases are cryptogenic with no identifiable underlying cause. Response to treatment is disappointing in most of the cases. We report a 60-year-old lady who presented with very severe type of painful legs and moving toes (PLMT) with no underlying cause.     

Probable dysimmune epilepsia partialis continua manifesting as epileptic moving toes syndrome: electroclinical features of a challenging case

Epilepsia partialis continua (EPC) is a rare form of focal status epilepticus. We describe a 22‐year‐old woman with EPC manifesting with isolated toe movements, prevalent over the left side and initially misdiagnosed as psychogenic, clinically almost indistinguishable from those observed in “painful legs and moving toes syndrome”. The continuous involuntary movements with EMG correlates of twitches lasting <100 ms, the sharp waves over fronto‐central regions on EEG, and the marked asymmetry in somatosensory evoked potentials with higher cortical amplitude over the right side following peripheral stimulation over the left foot confirmed the epileptic nature of the symptoms, leading to the diagnosis of EPC. The toe movements were markedly reduced following steroid therapy, whereas the infusion of immunoglobulins caused aseptic meningitis. Despite an extensive diagnostic work‐up (including a search for antibodies for paraneoplastic and autoimmune encephalitis), an ultimate aetiological diagnosis was not reached, although the dramatic response to corticosteroids strongly supported an underlying dysimmune pathophysiology. Diagnosing EPC can be challenging, especially if movements are confined to a very small body region or strongly resemble movements encountered in other conditions. EEG‐EMG monitoring should be performed in patients with continuous involuntary muscular jerks in order not to overlook a diagnosis of EPC. [Published with video sequences on www.epilepticdisorders.com ].     

Neuroleptic-induced "painful legs and moving toes" syndrome: successful treatment with clonazepam and baclofen

The syndrome of “painful legs and moving toes” is characterised by spontaneous causalgic pain in the lower extremities associated with peculiar involuntary movements of the toes and feet. It has been observed after a variety of lesions affecting the posterior nerve roots, the spinal ganglia and the peripheral nerves. The pathophysiology of the syndrome is unknown. I report a patient who developed the syndrome during treatment for schizophrenia with the antipsychotic agent molindone hydrochloride. The patient’s response to the combination of clonazepam and baclofen suggests that the pathophysiology of the “painful legs and moving toes” may be linked to impairment of spinal serotonergic and GABA functions.

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Sommario La sindrome delle gambe dolorose e dei piedi inquieti è caratterizzata da dolori spontanei di tipo causalgico alle estremità inferiori associati a movimenti involontari tipici dei piedi e delle dita. è stata osservata in una varietà di lesioni interessanti le radici posteriori, i gangli spinali e i nervi periferici. La patofisiologia della sindrome è sconosciuta. Riferisco qui di un paziente che presentò la sindrome durante un trattamento col farmaco antipsicotico molindone idrocloride. Il paziente era schizofrenico. La risposta positiva ad una associazione di clonazepam e baclofen suggerisce che la patofisiologia di questa sindrome debba essere riferita a un interessamento delle funzioni serotoninergiche e gabaergiche spinali.

     

Painful legs and moving toes

3 patients with the condition of "painful legs and moving toes" are reported. The etiology was unknown in 2 of them, but in 1 patient the symptoms were temporarily relieved by surgery for a lumbar herniated disc. The movements restarted 6 months after surgery. EMG studies showed near rhythmical muscle action potentials in the involved muscles of the foot at rates of 3.0, 2.5 and 0.5 cps respectively with a maintained reciprocal innervation. These spontaneous movements could only be suppressed for seconds. The EEG, nerve conduction studies and somatosensory evoked potentials were normal.     

Myoclonus with burning sensation in legs that remits with sympathetic blockade

Two patients with hitherto unrecognized spells of involuntary movements in legs are described. They occurred on dropping off to sleep, were preceded by a burning sensation and resembled myoclonus. Subcutaneous injection of epinephrine reproduced the spells. Neurogenic bladder of uninhibited type was noted on cystometry. Epidural or sympathetic nerve block of the lumbar region relieved all the symptoms including the neurogenic bladder. A few minutes before the spells, a rise in blood pressure and pulse rate was observed in one of the cases. Pathophysiological resemblance to painful legs and moving toes was pointed out, but more widespread involvement of the spinal cord was suspected.     

Painful hand and moving fingers

Summary A 52-year-old man developed a painful hand and moving fingers syndrome after trauma and amputation. Our observations and a similar published report indicate that symptoms similar to a syndrome of painful legs and moving toes can occur in the upper limbs.     

Painful legs and moving toes syndrome associated with Hashimoto's disease

A patient with Hashimoto' s disease presented with painful legs and moving toes (PLMT). The neurological and electrophysiological findings suggest that, in this case, PLMT syndrome is a variety of dystonic movement and is associated with Hashimoto's disease.     

Short‐ and intermediate‐term efficacy of buprenorphine TDS in chronic painful neuropathies

Abstract Buprenorphine is a potent opioid available as a transdermal delivery system (TDS) formulation. This open‐label study investigated its safety, tolerability, and efficacy in 30 patients with chronic painful neuropathy. Subjects with visual analogue scale (VAS) score ≥5 under stable analgesic treatment were entered. The starting dosage of 35 μg/h was increased up to 70.0 μg/h in case of unsatisfactory pain control as assessed by fortnightly visits. The primary endpoint was the number of patients achieving at least 30% pain relief at day 42 visit. Treatment was safe over the study period. Nine patients dropped out for side effects, mostly nausea and daily sleepiness. Buprenorphine TDS was well tolerated in 21 patients. Thirteen patients achieved >30% of pain relief at day 42 visit. Five patients needed to increase the dosage to 52.5 μg/h. Eight patients did not meet the primary outcome, but none allowed increasing the dosage to 70 μg/h, and four patients withdrew consent to continue the study before day 42 visit because of a ‘fear to become addicted,’ although 40% had obtained VAS reduction. In our study, which needs to be confirmed by a controlled trial, buprenorphine TDS induced clinically meaningful pain relief in about 40% of patients with chronic painful neuropathy, suggesting its use as a third‐line treatment.     

Hypertrophic neuropathy: atypical appearances resulting from the combination of type I hereditary motor and sensory neuropathy and diabetes mellitus

A nerve biopsy from a patient with type Ia hereditary motor and sensory neuropathy and diabetes mellitus showed hypertrophic changes of atypical appearance. The onion bulbs were composed of a central core of Schwann cells, with or without associated axons, embedded in concentrically arrayed layers of collagen fibrils. These were surrounded either by highly attenuated Schwann cell processes or by fibroblasts. The biopsy showed a severe loss of myelinated axons. It is suggested that it is necessary for the supernumerary Schwann cells of the onion bulbs to be stabilized by associated unmyelinated axons. If these are lost, the Schwann cells atrophy and disappear.     

A case of Dejerine-Sottas disease with prominent ataxia and brain stem involvement A clinical, electrophysiological, otoneurologic, and ultrastructural study

A case is presented of Dejerine-Sottas disease in a 12-year-old boy in which clinical signs made diagnosis of Friedreich's ataxia seem plausible.

Based on marked slowing of motor conduction velocity, the sural nerve biopsy findings of a hypertrophic neuropathy with hypo- and demyelination of the nerve fibres, as well as the clinical history, the diagnosis of Dejerine-Sottas disease was made.

ABR examination suggested involvement of brain stem at the roots and/or nuclei of the eighth cranial nerve, without involvement of higher structures.     

Signs of sympathetic and endothelial cell activation in the skin of patients with restless legs syndrome

ObjectivesTo evaluate skin biopsies of patients with early- and late onset restless legs syndrome (RLS) for concomitant small fiber neuropathy (SFN) and to determine cutaneous sympathetic innervation and microvascularization in comparison to healthy individuals.MethodsDensity of intraepidermal nerve fibers (IENFD), adrenergic nerve fibers and dermal capillaries was analyzed by immunofluorescence for PGP9.5, tyrosine hydroxylase and endothelial markers CD31 and CD105 in skin biopsies of 11 individuals with RLS and 8 age- and sex-matched controls.ResultsIENFD did not differ between RLS and controls, but two RLS patients with comorbid impaired glucose metabolism fulfilled morphometric criteria of SFN according to published normative values. In contrast, dermal nerve bundles of RLS patients showed an increased density of tyrosine hydroxylase⁺ adrenergic nerve fibers (p < 0.005). Moreover, an increased ratio between immature CD105⁺ and mature CD31⁺ endothelial cells within dermal capillaries was observed in RLS (p < 0.02).ConclusionsSFN, as a potential contributing factor for RLS, should be considered in patients with predisposing comorbidities presenting with burning or shooting pain, dysesthesias and impaired sensory and temperature perception. Evidence of an increased adrenergic innervation of the skin in RLS patients is in accordance with sympathetic hyperactivity while signs of endothelial cell activation may reflect an adaptive response to tissue hypoxia.     

Expression of capsaicin receptor immunoreactivity in human peripheral nervous system and in painful neuropathies

We describe the expression of the capsaicin receptor (TRPV1) in human peripheral nervous system (PNS) and its changes in sural nerve and skin nerve fibers of patients with painful neuropathy. Dorsal root ganglion (DRG), root, and spinal cord autopsy specimens from subjects without PNS diseases were immunoassayed with anti-TRPV1 antibodies. Bright-field and confocal microscope studies using anti-TRPV1, protein gene product 9.5 (PGP 9.5), and unique-beta-tubulin (TuJ1) antibodies were performed in skin biopsies from 15 healthy subjects and 10 painful neuropathies. The density of intraepidermal nerve fiber (IENF) labeled by each antibody was quantified. Sural nerve biopsies from three patients with painful, one patient with nonpainful diabetic neuropathy, and two patients with multifocal motor neuropathy used as controls were immunoassayed with anti-TRPV1 antibodies and investigated by immunoelectron microscopy. TRPV1 strongly labeled laminae I and II of dorsal horns, most small-size and some medium-size DRG neurons, and small-diameter axons of dorsal roots. In sural nerve, TRPV1 was expressed within the cytoplasm of most unmyelinated and some small myelinated axons, in the muscular lamina of epineural vessels, and in the endothelium of endoneurial vessels. The density of IENF labeled by TRPV1, PGP 9.5, and TuJ1 did not differ. TRPV1 colocalized with TuJ1 in all IENF and dermal nerve bundles. Painful neuropathies showed a diffuse loss of TRPV1-positive axons both in the sural nerve and in the skin. Our findings demonstrated that TRPV1 is normally expressed throughout the nociceptive pathway of PNS and that TRPV1-positive peripheral nerve fibers degenerate in painful neuropathies.