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     

Hypertrophic mononeuritis clinically presenting with painful legs and moving toes

A 40-year-old woman presented with progressive lower leg pain and spontaneous toe movement. The EMG showed a posterior tibial nerve mononeuropathy and continuous myokymic discharges in posterior tibial-innervated muscles. The MRI revealed a markedly enlarged posterior tibial nerve. Toe movements and myokymia were unaffected by the proximal transection of the lesion but ceased abruptly when the distal end of the fusiform "tumor" was resected, suggesting that spontaneous electrical foci may have been located along the nerve lesion. The markedly enlarged nerve segment contained edematous, swollen fascicles with marked Schwann cell onion-bulb lesions and angiocentric, lymphocytic, and lymphofollicular infiltration. This nerve lesion is an example of a newly recognized entity called hypertrophic mononeuritis.     

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.     

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 ].     

Contrasting painless and painful phenotypes of pediatric restless legs syndrome: a twin family study

ObjectiveThis study was designed to investigate painless and painful subsets of pediatric restless legs syndrome (RLS) for genetic influence and for associations with iron deficiency and common pediatric pain disorders.MethodsIn a twin family study, twins (3–18 years) and their oldest siblings, mothers and fathers completed questionnaires, assessing lifetime prevalence of RLS using current criteria, as well as history of iron deficiency and pediatric pain disorders. Subsets were categorized as RLS-Painless or RLS-Painful. Within twin pair analyses were conducted to assess familial and potential genetic effects for the defined subsets. Penalized maximum likelihood logistic regression was used to test familial associations. Random-effects logistic regression modeling was used in the total pediatric sample to investigate univariate and multivariate associations with the subsets.ResultsData were available for 2033 twin individuals (1007 monozygous (MZ), 1026 dizygous (DZ); 51.7% female), 688 siblings, 1013 mothers and 921 fathers. Odds ratios, correlations and casewise concordance were significantly higher in MZ than in DZ twins only for RLS-Painful. RLS-Painless, though familial (co-twin and mother), was not genetically influenced, but was independently associated with female sex (OR 0.52, p = 0.003), iron deficiency (OR 4.20, p < 0.001) and with persistent pain disorders (OR 2.28, p = 0.02). RLS-Painful was familial and was probably genetically influenced; was independently associated with non-migraine headaches (OR 2.70, p = 0.02) and recurrent abdominal pain (OR 2.07, p = 0.04).ConclusionsPediatric RLS was heterogeneous and was categorized into contrasting painless and painful phenotypes. RLS-Painless was associated with iron deficiency while RLS-Painful accounted for the heritability of RLS.     

Incidence of post-lumbar puncture syndrome reduced by reinserting the stylet: a randomized prospective study of 600 patients

The post-lumbar puncture syndrome (PLPS) can best be explained by prolonged spinal fluid leakage owing to delayed closure of a dural defect. Its incidence after spinal anaesthesia is much lower than after diagnostic lumbar puncture (LP). This difference could be caused by a strand of arachnoid, which might enter the needle with the outflowing cerebrospinal fluid (CSF) during diagnostic LP and upon removal of the needle be threaded back through the dura to produce prolonged CSF leakage. To find a technique that further reduces the incidence of PLPS, this hypothesis was tested by evaluating the effect that reinserting the stylet before removing the needle had on the incidence of PLPS. By reinserting the stylet to the tip of the needle, the hypothesized strand would be pushed out, thereby reducing the frequency of PLPS. Sprotte’s “atraumatic needle” (21 gauge) was used for LP. A total of 600 patients participated in the prospective study. They were randomized into two groups and questioned about their complaints every day for up to 7 days after the LP. All LPs were performed by two experienced neurologists (T.B., M.S.). In 300 patients, the stylet was reinserted to the tip of the needle; in the other 300 it was not reinserted. Whereas 49 of the 300 patients without reinsertion developed PLPS, only 15 of the 300 patients with reinsertion did. This significant difference (16.3 vs 5.0%, P < 0.005, chi square test) supports our hypothesis. On the basis of our results, we recommend reinserting the stylet before removing the needle in order to reduce the incidence of PLPS. Received: 30 September 1997 Received in revised form: 9 March 1998 Accepted: 20 March 1998     

Association of “top of the basilar” syndrome with megadolichobasilar artery. Clinical and neuroimaging evaluation

We describe the case of a patient with a history of trigeminal neuralgia who suddenly developed the “top of the basilar” syndrome. MRI disclosed ischemic lesions in the left paramedian mesencephalic tectum, in the left ventral thalamus, in the left occipital lobe and a megadolichobasilar artery (MDBA). The association of MDBA with the top of the basilar syndrome is rarely reported. We discuss the possible hemodynamic mechanism producing a top of the basilar syndrome in the presence of MDBA.

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Sommario Viene descritto il caso di un paziente, con una storia di nevralgia trigeminale, che ha improvvisamente presentato una “top of the basilar syndrome”. La RMN rilevava lesioni ischemiche a livello del tetto del mesencefalo in sede paramediana sinistra, nel talamo ventrale sinistro, nel lobo occipitale sinistro e la presenza di una megadolicobasilare. L'associazione di una megadolicobasilare con una “top of the basilar syndrome” è rara in letteratura. Gli autori discutono il possibile meccanismo emodinamico che può aver prodotto la sindrome in presenza di una anomala megadolicobasilare.

     

Intracranial microvascular decompression for "cryptogenic" hemifacial spasm, trigeminal and glossopharyngeal neuralgia, paroxysmal vertigo and tinnitus: I. Surgical technique and results

Intracranial microvascular decompression was performed in 21 out of 24 patients with hyperactive dysfunction of cranial nerves: 8 cases of hemifacial spasm, 12 of trigeminal neuralgia, 3 of glossopharyngeal neuralgia and 1 case of paroxysmal vertigo and tinnitus. In 21 cases an abnormal vascular loop was found to impinge on the root entry zone of the nerve in the brainstem. Dissection of this loop with decompression of the nerve resulted in long-lasting relief of symptoms in all but two patients who presented early recurrence; in one of these a second procedure was eventually successful. In two patients with trigeminal neuralgia a benign tumor of the cerebellopontine angle that had escaped preoperative diagnosis was present. Finally, in one case no compressive lesions were found. From the data of the literature and from our present experience microvascular decompression can be considered a safe as well as an effective procedure, affording a high success rate in conditions often or usually resistant to medical treatment and erroneously considered “idiopathic”.

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Sommario Sono stati operati con intervento di decompressione microvascolare dei nervi cranici 21 pazienti su 24 affetti da emispasmo del facciale (8 casi), nevralgia del trigemino (12 casi), nevralgia del glossofaringeo (3 casi), vertigini parossistiche (1 caso). In 21 casi fu riscontrata all'intervento un'ansa vascolare anomala comprimente il nervo all'emergenza dal tronco. La separazione dell'arteria dal nervo con tecnica microchirurgica ha consentito di risolvere i disturbi in tutti i casi eccetto due che presentarono una recidiva precoce: in uno di questi il reintervento fu risolutivo. In due pazienti con nevralgia del trigemino furono riscontrati due piccoli tumori benigni dell'angolo ponto-cerebellare non evidenziati dagli accertamenti neuroradiologici pre-operatori. In un caso non è stata riscontrata alcuna lesione compressiva. I risultati ottenuti confermano l'efficacia dell'intervento, e indicano come queste patologie siano erroneamente ritenute essenziali.

     

Intracranial microvascular decompression for "cryptogenic" hemifacial spasm, trigeminal and glossopharyngeal neuralgia, paroxysmal vertigo and tinnitus: II. Clinical study and long-term follow up

20 patients who had undergone microvascular decompression for the treatment of “idiopathic” trigeminal neuralgia (9 cases), hemifacial spasm, (7 cases), glossopharyngeal neuralgia (3 cases) and paroxysmal vertigo and tinnitus (1 case) were followed up for 25 months on average. Permanent relief of symptoms was observed in 19 (95%), with sparing of cranial nerve function. Analysis of the clinical data shows that the patients described in the present series did not differ from those considered to suffer from “idiopathic” cranial nerve dysfunction syndromes. The importance of vascular cross compression as etiological factor in such conditions is stressed and the pathophysiology discussed. The term “cryptogenic” applied to trigeminal neuralgia or hemifacial spasm thus needs revising. Lastly, the indications of microvascular decompression in the treatment of “cryptogenic” cranial nerve dysfunction syndromes are defined.

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Sommario Venti pazienti affetti da forme “essenziali” di nervralgia trigeminale (9 casi), emispasmo facciale (7 casi), nevralgia glosso-faringea (3 casi) e vertigine e tinnito parossistici (1 caso), operati di decompressione microvascolare, sono stati riesaminati ad una distanza media dall'intervento di 25 mesi. In 19 pazienti (95%) si è osservata la completa guarigione, in assenza di deficit funzionali a carico dei nervi cranici interessati. In base ai dati clinici e neuroradiologici, i pazienti qui descritti non sono differenziabili dal gruppo generale di malati con forme “idiopatiche” di nevralgia od emispasmo. Viene sottolineata l'importanza del fattore compressivo vascolare nel determinismo delle disfunzioni “essenziali” dei nervi cranici, e se ne discutono le interpretazioni fisiopatologiche. Si suggerisce quindi la necessità di rivedere il concetto di “idiopatico” applicato a tali condizioni morbose. Infine vengono definite le precise indicazioni ed il ruolo della decompressione microvascolare nella terapia della patologia “essenziale” dei nervi cranici.

     

Different iron deposition patterns in hemodialysis patients with and without restless legs syndrome: a quantitative susceptibility mapping study

ObjectiveBrain iron deposition in hemodialysis (HD) patients increases over time. Iron deficiency in gray matter nuclei has been reported to lead to idiopathic restless legs syndrome (RLS) symptoms. Regardless of unpleasant RLS sensations, the patterns of iron deposition between hemodialysis patients with RLS (HD-RLS) and hemodialysis patients without RLS (HD-nRLS) are still unclear. To evaluate the differences in iron deposition patterns between HD-RLS and HD-nRLS patients, we utilized quantitative susceptibility mapping (QSM).MethodsIn sum, 24 HD-RLS patients, 25 HD-nRLS patients and 30 age- and sex-matched healthy controls (HCs) were enrolled. The QSM was used to assess susceptibility values of the regions of interest (ROIs), including the caudate nucleus (CN), putamen (PUT), globus pallidus (GP), thalamus (THA), substantia nigra (SN), red nucleus (RN) and dentate nucleus (DN).ResultsHD duration was significantly longer in HD-RLS patients than in HD-nRLS patients (P < 0.05). The susceptibility of HD-RLS and HD-nRLS patients in PUT was higher than that in HCs (P < 0.05), illustrating elevated iron content in the nucleus. Compared with HD-nRLS patients, HD-RLS patients demonstrated reduced susceptibility in CN and PUT (both P < 0.05). Compared with HCs, HD-RLS patients displayed decreased susceptibility in DN (P < 0.05).ConclusionsDifferent iron deposition patterns between HD-RLS and HD-nRLS patients in PUT and DN, which further support disturbed sensory processing in RLS, may be involved in RLS pathogenesis in HD patients.     

One‐year treatment with standard and sustained‐release levodopa: Appropriate long‐term treatment of restless legs syndrome?

To investigate the long-term efficacy and safety of sustained-release (SR) in combination with regular-release (RR) levodopa/benserazide in the treatment of restless legs syndrome (RLS), an open-label, prospective, extension study of a preceding double-blind crossover trial was performed for 12 months. Twenty-three severely disturbed RLS patients (7 men, 16 women) received a combination of RR and SR levodopa. Patients were treated on average for 10 months with a mean daily dose of 203 +/- 101 mg of RR and of 185 +/- 93 mg of SR levodopa. The mean daily total dose was 388 +/- 162 mg levodopa. Efficacy was documented using patient's rating scales, sleep diaries, and investigator's global ratings with the Clinical Global Impressions (CGI). Ten of 23 patients completed the 1-year extension. Between baseline of the crossover trial and endpoint of the extension study (last-observation-carried-forward method, intention-to-treat population), quality of sleep improved (+3.5 +/- 1.9, 7-point scale), sleep latency was shortened (-131 +/- 152 minutes), and total sleep time lengthened (+ 190 +/- 136 minutes). Severity of RLS at time of falling asleep (-6.5 +/- 3.4, 11-point scale) and during the night (-6.0 +/- 3.5) was markedly lower at the end of the extension but severity of RLS during the day (+1.9 +/- 5.0) slightly increased. Of 13 dropouts, 8 patients discontinued therapy because of worsening RLS during the day. This trial shows that long-term treatment with the combination of RR and SR levodopa/benserazide in RLS patients with late-night problems was efficacious and not limited by tolerability problems in 40% of patients, whereas in the majority of patients, aggravating daytime problems required termination of the levodopa therapy within the 1-year treatment period.     

Prevalence and clinical characteristics of restless legs syndrome in diabetic peripheral neuropathy: comparison with chronic osteoarthritis

BackgroundThe prevalence of restless legs syndrome (RLS) in patients with peripheral neuropathy has been reported to be higher than that of the general population in some studies, which suggests an association between neuropathy and RLS, but not all studies show increased RLS with neuropathy. These differences may reflect adequacy of the diagnosis, effects of chronic pain complicating the diagnosis, or population differences. Moreover, if there is increased risk for RLS with neuropathy, it may reflect consequences of the chronic pain rather than other aspects of diabetes mellitus (DM). Therefore, we investigated the effects of diagnosis rigor on the estimated prevalence of RLS in patients with diabetic peripheral neuropathy (DPN) and those with chronic leg pain from osteoarthritis (OA), and then we compared the RLS prevalence in these two populations with each other and with population prevalence for Korea.MethodsOur study is a prospective case-control study of 199 patients with DPN and 220 patients with OA. After evaluating the presence of RLS in these subjects using the diagnostic criteria of the International RLS Study Group, we confirmed the diagnosis of RLS through face-to-face interviews using the 18-item Hopkins Diagnostic Questionnaire, which removes RLS mimics; and through independent examinations by two neurologists.ResultsOf the 199 subjects with DPN, 44 (22%) appeared to have RLS from their answers on the 4-item RLS diagnostic questionnaire compared to 8 (3.6%) of 220 subjects with OA. However, the prevalence of RLS in the DPN group dropped to 16 (8%) subjects but stayed at 8 (3.6%) OA subjects when using the Hopkins Telephone Diagnostic Interview (HTDI) adapted for clinical interview. The RLS prevalence determined by HTDI remained significantly higher (P = .042) in the DPN group compared to the OA group and was twice that reported for the general Korean population (8% vs 3.9%). Among subjects with DPN, those with RLS were older (68.06 ± 8.43 years vs 62.46 ± 11.05 years; P = .049) and had higher pain scores (visual analog scale [VAS], 4.69 ± 2.52 vs 2.72 ± 2.12; P = .002). The quality of sleep (MOS [Medical Outcomes Study] sleep scale) and health-related quality of life (QoL) (total score on the 36-Item Short-Form Health Survey [SF-36]) showed no significant difference between the two groups.ConclusionsThe prevalence of RLS in patients with DPN cannot be accurately assessed with only the four diagnostic criteria interview, but the prevalence was higher than expected for Koreans from the general population prevalence and also was higher than occurred with OA patients with chronic leg pains when accurately assessed with a structured interview. Chronic leg pain from OA does not significantly complicate RLS diagnosis, and chronic pain itself does not explain the increased RLS prevalence in diabetic neuropathy.     

Gabapentin enacarbil,pregabalin and rotigotine are equally effective in restless legs syndrome: a comparative meta‐analysis

To synthesize evidence from available randomized controlled trials (RCT) to compare the efficacies of dopaminergic drugs (pramipexole, ropinirole and rotigotine) and α‐2‐δ ligands (gabapentin enacarbil and pregabalin) for the treatment of restless legs syndrome (RLS). We searched PubMed for all eligible RCTs. Network meta‐analysis using frequentist methodology with random effect models was performed for mean changes in scores on the International RLS Study Group Rating Scale (IRLS) and for responder rates on Clinical Global Impressions‐Improvement (CGI‐I); analyzed as odds ratio (OR). Network meta‐analysis of mean changes in IRLS data from 35 studies with 7333 participants showed that all treatments, in specific gabapentin enacarbil, followed by pregabalin and rotigotine were superior to placebo [mean reduction in IRLS scores: ?5.31 (?6.74 to ?3.87), ?5.20 (?6.91 to ?3.49), 5.17 (3.73–6.61), respectively] but there were no significant differences between active treatments. Network meta‐analysis of 5137 participants from 24 studies showed that gabapentin enacarbil and rotigotine were associated with the highest CGI‐I response rates [ORs: 5.68; (95% CI, 4.14–7.21); and 4.68 (2.87–6.49), compared to placebo, respectively]. No significant inter‐treatment differences exist, except for that between gabapentin enacarbil and ropinirole. Based on IRLS scores and CGI‐I response rates, while gabapentin enacarbil, pregabalin and rotigotine stand out as the most efficacious of all examined drugs, it is noteworthy that no significant inter‐treatment differences exist, except for that between gabapentin enacarbil and ropiniriole (for CGI‐I response rates).     

Acute double-blind,placebo-controlled sleep laboratory and clinical follow-up studies with a combination treatment of rr-L-dopa and sr-L-dopa in restless legs syndrome

In a double-blind, placebo-controlled randomized crossover trial, the acute efficacy of a combination treatment of 100 mg regular-release (rr) and 100 mg sustained-release (sr) L-dopa/benserazide in RLS was investigated by means of sleep laboratory methods, with a subsequent open clinical follow-up for 4 weeks. 21 RLS patients classified according to ICSD and IRLSSG criteria were included; 18 completed the study. Objective sleep quality was determined by polysomnography (PSG) in 3 subsequent nights (adaptation/screening, placebo and drug night), subjective sleep and awakening quality was evaluated by rating scales, objective awakening quality by psychometric tests. Clinical follow-up consisted of daily ratings of subjective sleep and awakening quality (SSA) and VAS for RLS symptomatology ratings, completion of the RLS (IRLSSG) Scale weekly and the Zung Depression (SDS) and Anxiety (SAS) Scale, Quality of Life Index, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale before and after therapy. Acute L-dopa/benserazide significantly (p < 0.001) and markedly (75%) decreased the target variable PLM/h of sleep as well as all other RLS/PLM variables, but failed to improve objective sleep efficiency and subjective sleep quality in comparison to placebo. After 4 weeks of therapy, however, subjective sleep and awakening quality also improved significantly. While RLS/PLM measures showed an immediate significant and marked response to the combination therapy subjective sleep quality only improved after chronic treatment.