Hierro intravenoso en la terapia del síndrome de piernas inquietas / Intravenous iron for restless legs syndrome. Report of five cases

Restless legs syndrome (RLS) may severely affect the quality of life of patients. A deficient iron incorporation into the central nervous system has an important role in the pathophysiology of RLS. Severely affected patients may not respond to current therapeutic options. We report a preliminary experience with five patients with severe RLS and low serum ferritin levels who did not improve with oral iron. All were treated with 1 g of intravenous iron carboxymaltose. They experienced a marked improvement in symptoms, evident even during the first week of therapy that had persistent after up to two years of follow-up. A significant change in the RLS severity scale was observed after intravenous iron. Serum ferritin levels increased in all of them. Intravenous iron could be a therapeutic option for patients with severe RLS.

Síndrome de piernas inquietas en niños: caracterización clínica / Characterization of restless leg syndrome in children

El Síndrome de piernas inquietas (SPI) o Enfermedad de Willis­Ekbom, es una condición neurológica que afecta al 2-4% de los niños en edad escolar. Etiológicamente se ha relacionado al metabolismo del hierro y a factores genéticos entre otros. En niños aun es una patología poco diagnosticada. Trabajo observacional descriptivo, en el cual se realiza caracterización clínica, según criterios internacionales, en 14 pacientes menores de 18 años, 9 varones. Edad promedio 8 años. Sintomatología inicial variada, desde resistencia a ir a la cama, hasta dibujar sus molestias. En 10 se comprobó déficit de hierro. En 11 pacientes se realizó un polisomnograma, 10 de ellos con un índice elevado de movimientos periódicos de extremidades. El uso de pregabalina y aporte de hierro fue el tratamiento más utilizado. Dos pacientes tenían padres diagnosticados con SPI.

Abstract. The Restless Legs Syndrome (RLS) or Willis-Ekbom Disease is a neurological condition that affects 2-4% of school-age children. Its etiology has been related to the metabolism of iron and genetic factors among others. In children it is still a frequently undiagnosed disorder. This is a descriptive observational report, in which clinical characterization is carried out according to international criteria in 14 patients under 18 years old, 9 boys. Average age is 8 years old. The initial symptomatology was varied, from resistance to comply with bedtime, to drawing their discomfort. In 9, iron deficiency was found. A polysomnogram was performed in 11 patients, 10 of which had a high periodic limb movements index. The use of pregabalin and supplementary iron were the most used treatments. Two patients had parents diagnosed with RLS.

The Parkinson's disease and restless legs syndrome/Willis-Ekbom disorder link: evidences, biases and clinical relevance / A conexão doença de Parkinson: síndrome das pernas inquietas / doença de Willis-Ekbom: evidências, vieses e relevância clínica

ABSTRACT Parkinson's disease (PD) and restless legs syndrome/Willis-Ekbom disorder (RLS/WED) are relatively common diseases in the realm of movement disorders. The fact that both may, as expected, co-occur and typically share a similar remarkable response to dopaminergic treatment raised the interest in exploration of additional shared features that throughout the years cruised fields as diverse as phenomenology, epidemiology, genetics, pathology, and clinical studies. In this review, we describe and critically examine the evidence and biases of a conceivable overlap of these two disorders, trying to shed light onto two main sources of confusion: (1) are PD and RLS/WED reciprocal risk factors? and (2) what are the main mimics of RLS/WED in PD?

RESUMO A doença de Parkinson (DP) e a síndrome das pernas inquietas/doença de Willis-Ekbom (SPI/DWE) são doenças relativamente comuns no campo dos distúrbios do movimento. O fato de que ambas podem, como esperado, ocorrer de forma simultânea e usualmente apresentarem resposta favorável ao tratamento dopaminérgico levaram ao interesse em explorar características compartilhadas adicionais. Ao longo dos últimos anos, essa busca percorreu campos diversos como a fenomenologia, epidemiologia, genética, patologia e estudos clínicos. Nesta revisão, analisamos e discutimos criticamente as evidências e os vieses de sobreposição concebíveis dessas duas doenças, tentando esclarecer duas perguntas sem resposta precisa até o momento: (1) DP e SPI/DWE representam fatores de risco recíprocos? e (2) quais são os principais mimetizadores da SPI/DWE na DP?

Síndrome de piernas inquietas/Willis Ekbom desde la mirada del psiquiatra / Restless legs syndrome from the perspective of psychiatry

Restless Legs Syndrome (RLS) or Willis-Ekbom Disease is an under-diagnosed chronic and progressive primary sensory-motor disorder. It can lead to severe sleep disturbances, a usual cause of consultation. It is characterized by an urgent need to move the legs in resting situations, a cardinal symptom that is usually accompanied by an unpleasant sensation in legs. These symptoms appear or aggravate at the end of the day and in resting situations and are alleviated with movement. Based on these clinical characteristics, it has been defined as a quiescegenic focal akathisia. The diagnosis is essentially clinical. As a guide, there are five cardinal diagnostic criteria. The treatment consists of non-pharmacological measures and the use of medications such as dopamine agonists. Despite the treatment, the symptoms persist in 40% of patients. Psychiatrists should be aware of the syndrome since many drugs used by them such as antipsychotics, antidepressants and anxiolytics can worsen the symptoms. Moreover, the syndrome may be associated with depressive and anxiety diseases.

Síndrome de piernas inquietas (enfermedad de Willis-Ekbom): seguimiento a largo plazo de una serie de pacientes / Restless legs syndrome: long-term follow-up of a series of patients

Background: Restless legs syndrome (RLS) affects 10% of the general population. Aim: To analyze a series of patients with a minimum follow-up period of four years, treated during an interval of 14 years. Material and Methods: Retrospective analysis of medical records of 200 patients assessed and followed by the authors at a private outpatient clinic. Results: Fifty patients aged 25 to 90 years (34 females), who had a mean follow-up of 6,3 years (range 4-14 years), were selected. Sixty percent responded to therapy that initially consisted in dopamine agonists in 78% of cases. Thirty four percent remained symptomatic and 4% worsened. RLS severity scale improved from an initial score of 19,2 to 12,5 at the last follow-up visit (p < 0.05). Thirty-three patients (66%) experienced an overall worsening of symptoms beyond pretreatment levels during follow-up. The strategies to overcome this augmentation were the change to another agonist, use of ligands such as pregabalin and gabapentin, opioids and iron. Low ferritin was common in most of the patients in whom it was measured (24 of 45 results), mainly in those with augmentation (p < 0,05). Six percent of patients treated with dopamine agonist developed an impulse control disorder. Conclusions: RLS is a treatable condition during a long period of follow-up in most patients. We found a high rate of potentiation at presentation which can be explained by the inadequate use of high doses of dopaminergic agents.

Análisis de impacto presupuestal de pramipexol comparado con levodopa como terapia de primera línea para pacientes con síndrome de piernas inquietas en Colombia / Budget impact analysis of pramipexole compared to levodopa as first-line therapy for patients with restless legs syndrome in Colombia

Tecnologías evaluadas: Nuevas: pramipexol y cabergolina; Actuales: levodopa (en combinación con carbidopa). Población: Pacientes mayores de 18 años con síndrome de piernas inquietas. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costo por mg de los medicamentos. Fuente de costos: Sistema de información de Precios de Medicamentos y Dispositivos Médicos - SISMED. Escenarios: En la construcción de escenarios se consideró una participación de\r\nmercado más alta para pramipexol en comparación con levodopa. Lo anterior a partir de las recomendaciones resultado de la consulta con expertos y la participación de mercado de los medicamentos en el SISMED. \r\nResultados: Para la inclusión en el POS de pramipexol y cabergolina como terapia de primera línea para pacientes con síndrome de piernas inquietas en Colombia, se requeriría una inversión de $21.708.230.419 en el año 1 y de $53.499.840.477 en el año 3. En el caso que los medicamentos del escenario nuevo sean incluidos con un precio común basado en las metodologías de grupos terapéuticos del Ministerio de Salud y protección Social, el impacto presupuestal sería el mismo con una inversión de $21.708.230.419 en el año 1 y $53.499.840.477, en el año 3.(AU)

Efectividad y seguridad de Pramipexol comparado con Levodopa, Pergolida, Cabergolina, Ropinirole para el tratamiento del Síndrome de Piernas Inquietas / Effectiveness and safety of Pramipexole compared to Levodopa, Pergolide, Cabergoline, Ropinirole for the treatment of Restless Legs Syndrome

IIntroducción: el Síndrome de Piernas Inquietas (SPI) se define como un trastorno neurológico que afecta de un 5 % a un 15% de la población general, de causa desconocida, incurable y de evolución crónica, con afectación del sueño y la calidad de vida en alerta. Se cuenta con tratamientos para aliviar los síntomas que afectan la calidad de vida, una primera línea de tratamiento son los agonistas dopaminérgicos entre ellos la Levodopa, el Pramipexol y la Pergolida (8), (9), (10). Objetivo: evaluar la efectividad y seguridad del pramipexol, comparado con otros agonistas dopaminergicos para el tratamiento del Síndrome de Piernas Inquietas (RSL). Metodología: la evaluación fue realizada de acuerdo al protocolo definido previamente por el grupo desarrollador el cual incluye una revisión sistemática de la literatura en MEDLINE, EMBASE, LILACS, COCHRANE y Google para dar respuesta a la pregunta de investigación desarrollada bajo la estrategia PICOT en compañía de expertos técnicos y metodológicos. En el estudio de Scholz con el uso del pramipexol se observó una diferencia de medias de -5.16 [IC95% -6.87 a -3.45] comparado con placebo en la escala de síntomas IRLS (I²= 76%). Los agonistas dopaminérgicos comparados con el placebo produjeron una diferencia de medias en la reducción del PLMSI de −22.38 (IC95% −27.82 a −16.94) por hora de sueño (I² = 73%). El Pramipexol produjo contra placebo una diferencia de medias de -30.47 [IC9% -51.58 a -9.35] (I² = 85%) en el Cambio en el PLMSI (calidad del sueño, a favor de pramipexol. Los agonistas dopaminérgicos comparados con placebo reportaron una diferencia de medias de 0.4 [IC95% 0.33 a 0.47] a favor de los agonistas dopaminergicos respecto a la calidad del sueño autoreportada. En un análisis de subgrupos por medicamentos, el pramipexol produjo contra placebo un cambio en la calidad del sueño autoreportada con una diferencia de medias de 0.44 [IC: 0.33, 0.54], a favor de pramipexol. Los agonistas dopaminérgicos produjeron mejoría en la calidad de vida comparado contra placebo con una diferencia de medias de 0.34 [IC95% 0.23 a 0.44] (I²= 61%). En un análisis de subgrupos por medicamento, el pramipexol produjo mejoría en la calidad de vida comparado contra placebo con una diferencia estandarizada de medias de 0.30 [IC95% 0.13 a 0.47]. Los agonistas dopaminérgicos (cabergolina o pramipexol) comparados con levodopa produjeron un cambio en la línea de base del IRLS con una diferencia de medias de -5.25 [IC95% -8.40 a -2.10] (I²= 55%). En comparaciones indirectas dentro del estudio Ying Sun el pramipexol versus el ropirinole mostró una diferencia de medias en la escala de síntomas IRLS de -1.48 (IC95% -4.47 a 0.45) sin embargo esta diferencia no fue estadísticamente significativa. Respecto a la seguridad, los eventos adversos fueron más frecuentes en el grupo de pacientes que recibió agonistas dopaminérgicos comparado con los pacientes que recibieron placebo con un OR de 1.82 [IC95% 1.59 a 2.08]. Los retiros por eventos adversos fue superior en el grupo de agonistas dopaminergicos versus placebo, con un OR 1.82, (IC95% 1.35 a 2.45), diferencia estadísticamente significativa y mostró una heterogeneidad moderada (I² = 41%). Los retiros por eventos adversos fue superior en el grupo de agonistas dopaminergicos versus placebo, con un OR 1.82, (IC95% 1.35 a 2.45), diferencia estadísticamente significativa y mostró una heterogeneidad moderada (I² = 41%). En un análisis de subgrupos por medicamentos, se reportaron más retiros con pramipexol que con placebo con un OR de 1.11 [IC95% 0.66 a 1.87], esta diferencia no fue estadísticamente significativa con una heterogeneidad moderada (I²= 44%). Conclusiones: Efectividad: Los agonistas dopaminergicos, dentro de los cuales está incluido el pramipexol, son más efectivos que el placebo en el tratamiento de las personas con RLS para los desenlaces de escala de síntomas IRLS, la reducción del PLMSI , la calidad de sueño autoreportada y calidad de vida. En un análisis por subgrupos dentro de la comparación entre agonistas dopaminergicos y el placebo, el pramipexol se mostró más efectivo que el placebo en los desenlaces del cambio del PLMSI, calidad del sueño y en la calidad de vida. Los agonistas dopaminergicos, dentro de los cuales está incluido el pramipexol, son más efectivos que la levodopa para los desenlaces de escala de síntomas IRLS. Al comparar el pramipexol de forma indirecta con el ropirinole (agonista dopaminergico) no se observaron diferencias estadísticamente significativas. Seguridad: Los eventos adversos son más frecuentes en el de grupo tratamiento con agonistas dopaminergicos (dentro de los cuales se encuentra el pramipexol) comparado con placebo. No se encontraron diferencias en seguridad entre el pramipexol y el placebo.(AU)

Saint John's wort, an herbal inducer of the cytochrome P4503A4 isoform, may alleviate symptoms of Willis-Ekbom's disease

OBJECTIVE: Certain drug classes alleviate the symptoms of Willis-Ekbom's disease, whereas others aggravate them. The pharmacological profiles of these drugs suggest that drugs that alleviate Willis-Ekbom's disease inhibit thyroid hormone activity, whereas drugs that aggravate Willis-Ekbom's disease increase thyroid hormone activity. These different effects may be secondary to the opposing actions that drugs have on the CYP4503A4 enzyme isoform. Drugs that worsen the symptoms of the Willis-Ekbom's disease inhibit the CYP4503A4 isoform, and drugs that ameliorate the symptoms induce CYP4503A4. The aim of this study is to determine whether Saint John's wort, as an inducer of the CYP4503A4 isoform, diminishes the severity of Willis-Ekbom's disease symptoms by increasing the metabolism of thyroid hormone in treated patients. METHODS: In an open-label pilot trial, we treated 21 Willis-Ekbom's disease patients with a concentrated extract of Saint John's wort at a daily dose of 300 mg over the course of three months. RESULTS: Saint John's wort reduced the severity of Willis-Ekbom's disease symptoms in 17 of the 21 patients. CONCLUSION: Results of this trial suggest that Saint John's wort may benefit some Willis-Ekbom's disease patients. However, as this trial was not placebo-controlled, the extent to which Saint John's wort is effective as a Willis-Ekbom's disease treatment will depend on future, blinded placebo-controlled studies. .

Comorbidities, medications and depressive symptoms in patients with restless legs syndrome and migraine / Comorbidades, medicações e sintomas depressivos em pacientes com síndrome das pernas inquietas e enxaqueca

OBJECTIVE: The pathophysiology of migraine and restless legs syndrome (RLS) seems to involve inherited mechanism and dysfunction of the dopaminergic system. Previous articles have shown that the frequency of RLS is higher in migraine patients than in controls. We conducted a study to evaluate comorbidities, medication used and depressive symptoms that can explain the relation between migraine and RLS. METHODS: A case-control study was performed in which patients with migraine (n=72) and a control group without migraine (n=72) were interviewed. Data including RLS diagnosis, depressive symptoms, comorbidities and drugs used were evaluated. RESULTS: There was a significant association between migraine and RLS (p=0.01), but comorbidities such as diabetes, hypertension, anemia and drugs used did not explain this association. Depression scores, as measured by the Beck Depression Inventory, were higher in migraine patients with RLS (p =0.04). CONCLUSION: No specific factors explaining the association between migraine and RLS were found. Symptoms of depression were more frequent in patients with migraine and RLS.

OBJETIVO: A fisiopatologia da enxaqueca e da síndrome das pernas inquietas (SPI) parece envolver mecanismos genéticos e disfunção do sistema dopaminérgico. Artigos anteriores mostraram que a frequência de SPI em pacientes com enxaqueca é maior do que nos controles. Desenvolvemos um estudo para avaliar comorbidades, medicamentos utilizados e sintomas depressivos em pacientes com migrânea e SPI. MÉTODOS: Foi desenvolvido um estudo de caso-controle. Foram entrevistados pacientes com enxaqueca (n=72) e sujeitos de um grupo controle (n=72). Foram avaliados dados incluindo diagnóstico de SPI, sintomas depressivos, comorbidades e medicamentos usados. RESULTADOS: Houve associação significativa entre enxaqueca e SPI (p=0,01). Comorbidades como diabetes, hipertensão, anemia ou drogas utilizadas não explicam esta associação. Escores de depressão, medidos pelo Inventário de Beck, foram mais altos em pacientes com enxaqueca e SPI (p=0,04). CONCLUSÃO: Não foram encontrados fatores específicos que explicam a associação entre enxaqueca e SPI. Sintomas de depressão foram mais frequentes em pacientes com enxaqueca e SPI.

Clinical correlates of the restless legs syndrome / Correlações clínicas da síndrome das pernas inquietas

OBJECTIVE: To determine the clinical correlates of the restless legs syndrome (RLS) in a Brazilian sleep disorders center. METHODS: We retrospectively studied 118 patients with RLS from January, 2004, to December, 2010. The analyzed variables were: age at disease onset, gender, race, years of school instruction, primary and secondary RLS, and treatment options. RESULTS: Among the studied patients, 83.9% were women with a female/male sex ratio of 5:1. Mean age of the patients at symptom onset ± standard deviation was 41.7±17.9 years-old. The primary RLS was found in 85% of patients. The other 15% remainders consisted of secondary forms, and they were associated with neuropathy, iron deficiency anemia, end-stage renal disease, or Parkinson's disease. Drug therapy for RLS was introduced in 67% of patients. CONCLUSIONS: Most patients presented primary RLS with an early disease onset. Further epidemiological studies are welcomed to provide better information on secondary RLS in Brazil.

OBJETIVO: Determinar as correlações clínicas da síndrome das pernas inquietas (SPI) em um centro brasileiro de distúrbios de sono. MÉTODOS: Foram estudados retrospectivamente 118 pacientes com SPI atendidos entre janeiro de 2004 e dezembro de 2010. As variáveis analisadas compreendiam: idade ao início da doença, sexo, raça, escolaridade, SPI primária e secundária e tratamento da SPI. RESULTADOS: Do total de pacientes estudados, 83,9% eram mulheres e a razão mulher∕homem foi de 5:1. A média de idade dos pacientes ± desvio padrão de quando iniciaram sintomas da SPI foi de 41,7±17,9 anos. Oitenta e cinco por cento dos pacientes apresentaram SPI primária. Os restantes 15% apresentaram a forma secundária, que estava associada à neuropatia periférica, anemia por deficiência de ferro, insuficiência renal crônica e doença de Parkinson. Foi introduzida medicação para SPI em 67% dos pacientes. CONCLUSÕES: A maioria dos pacientes apresentou SPI primária com início precoce da doença. Mais estudos epidemiológicos são necessários para prover informações sobre as causas secundárias de SPI no Brasil.

Restless legs syndrome in subjects with a knee prosthesis: evidence that symptoms are generated in the periphery

OBJECTIVE: There are no data adressing the prevalence of restless legs syndrome in subjects who have knee prosthesis. Therefore, we conducted a cross-sectional survey of subjects who underwent knee prosthesis surgery. METHOD: A total of 107 subjects (30 male, 77 female) were interviewed over the telephone regarding restless legs syndrome symptoms. If the patients exhibited symptoms of the syndrome, we conducted face-to-face interviews. Lastly, a therapeutic test with pramipexole was proposed for each subject. RESULTS: In our cohort, 7 males (23 percent) and 30 females (39 percent) had restless legs syndrome. Of these, 6 males and 23 females were submitted to face-to-face-interview. Of the males, 5 (83 percent) had restless legs after the knee surgeryexclusively in the operated leg- and reported no family restless legs history. One man had a prior case of bilateral restless legs syndrome, a positive family history and claimed exacerbation of symptoms in the operated leg. Among the females, 16 (69 percent) had restless legs prior to surgery. A total of 10 female patients reported bilateral symptoms, with fewer symptoms in the operated leg, while 6 displayed a worse outcome in the operated leg. The 7 females (31 percent) without restless legs prior to surgery and without a family history experienced symptoms only in the operated leg. All subjects responded favorably to the pramipexole therapeutic test. CONCLUSION: Our results suggest that secondary unilateral restless legs syndrome may ensue from knee prosthesis surgery and that the symptoms are generated in the peripheral nervous system.

Imbalance between thyroid hormones and the dopaminergic system might be central to the pathophysiology of restless legs syndrome: a hypothesis

Data collected from medical literature indicate that dopaminergic agonists alleviate Restless Legs Syndrome symptoms while dopaminergic agonists antagonists aggravate them. Dopaminergic agonists is a physiological regulator of thyroid-stimulating hormone. Dopaminergic agonists infusion diminishes the levels of thyroid hormones, which have the ability to provoke restlessness, hyperkinetic states, tremors, and insomnia. Conditions associated with higher levels of thyroid hormones, such as pregnancy or hyperthyroidism, have a higher prevalence of Restless Legs Syndrome symptoms. Low iron levels can cause secondary Restless Legs Syndrome or aggravate symptoms of primary disease as well as diminish enzymatic activities that are involved in dopaminergic agonists production and the degradation of thyroid hormones. Moreover, as a result of low iron levels, dopaminergic agonists diminishes and thyroid hormones increase. Iron therapy improves Restless Legs Syndrome symptoms in iron deprived patients. Medical hypothesis. To discuss the theory that thyroid hormones, when not counterbalanced by dopaminergic agonists, may precipitate the signs and symptoms underpinning Restless Legs Syndrome. The main cause of Restless Legs Syndrome might be an imbalance between the dopaminergic agonists system and thyroid hormones.

Anticonvulsants to treat idiopathic restless legs syndrome: systematic review / Anticonvulsivantes para a síndrome das pernas inquietas idiopática: revisão sistemática

BACKGROUND: Restless legs syndrome (RLS) is a sensory motor disorder characterized by a distressing urge to move the legs and sometimes also other parts of the body usually accompanied by a marked sense of discomfort or pain in the leg or other affected body part. Many treatments have been used to minimize the discomfort of the disease, among them the anticonvulsant therapy. AIM: This review aims to evaluate the efficacy and safety of anticonvulsant treatment for idiopathic RLS. METHOD: Systematic review of randomized or quasi-randomized, double blind trials on anticonvulsant treatment for RLS. Outcomes: relief of RLS symptoms, subjective and objective sleep quality, quality of life, and adverse events associated with the treatments. RESULTS: A total of 231 patients were randomized in three cross over studies and one parallel study. Three studies with carbamazepine, one with sodium valproate, and one with gabapentin, and they were very heterogeneous so we could not perform a metanalyses. CONCLUSIONS: There is no scientific evidence on RLS treatment with anticonvulsants for clinical practice.

CONTEXTO: A síndrome das pernas inquietas (SPI ) é uma desordem caracterizada por um impulso de mover as pernas e as vezes outras partes do corpo acompanhado geralmente por desconforto ou da dor nas pernas ou em outra parte afetada. Muitos tratamentos tem sido utilizados para aliviar o desconforto causado pela doença entre eles os anticonvulsivantes. OBJETIVO: Este estudo objetivou avaliar a eficácia e segurança do tratamento da SPI com as drogas anticonvulsivantes. MÉTODO: Revisão sistemática de ensaios clínicos randomizados ou quasi-randomizados, duplo-cegos para o tratamento com anticonvulsivantes para SPI. Desfechos: alívio dos sintomas da SPI, qualidade subjetiva e objetiva do sono, qualidade de vida e efeitos adversos relacionados ao tratamento. RESULTADOS: Um total de 231 pacientes foram randomizados em três estudos cross-over e um estudo paralelo. Três estudos avaliaram a carbamazepina, um estudo avaliou o ácido valpróico e o outro a gabapentina, eles eram muito heterogêneos, o que impossibilitou a metanálise dos resultados. CONCLUSÃO: Não existe evidência científica, que o tratamento da SPI com anticonvulsivantes é eficaz e seguro, para a prática clínica.

Síndrome das pernas inquietas: diagnóstico e tratamento: opinião de especialistas brasileiros / Restless legs syndrome: diagnosis and treatment: opinion of Brazilian experts

Este artigo contém as conclusões de reunião de 17-18 de novembro de 2006 do Grupo Brasileiro de Estudo em Síndrome das Pernas Inquietas (GBE-SPI) sobre diagnóstico e tratamento de SPI. Reiterou-se que se trata de condição de diagnóstico exclusivamente clínico, caracterizada por sensação anormal localizada, sobretudo, mas não exclusivamente, em membros inferiores, com piora noturna e alívio por movimentação da parte envolvida. Agentes terapêuticos com eficácia comprovada por estudos classe I são agonistas dopaminérgicos, levodopa e gabapentina enquanto que ácido valpróico de liberação lenta, clonazepam, oxicodona e reposição de ferro têm eficácia sugerida por estudos classe II. As recomendações do GBE-SPI para manejo de SPI primária são medidas de higiene do sono, suspensão de agentes agravantes de SPI, tratamento de comorbidades e agentes farmacológicos. Para estes as drogas de primeira escolha são agentes dopaminérgicos; segunda escolha são gabapentina ou oxicodona; e terceira escolha são clonazepam ou ácido valpróico de liberação lenta.

This article contains the conclusions of the November 17-18, 2006 meeting of the Brazilian Study Group of Restless Legs Syndrome (GBE-SPI) about diagnosis and management of restless legs syndrome (RLS). RLS is characterized by abnormal sensations mostly but not exclusively in the legs which worsen in the evening and are improved by motion of the affected body part. Its diagnosis is solely based on clinical findings. Therapeutic agents with efficacy supported by Class I studies are dopamine agonists, levodopa and gabapentine. Class II studies support the use of slow release valproic acid, clonazepan and oxycodone. The GBE-SPI recommendations for management of SPI are sleep hygiene, withdrawal of medications capable of worsening the condition, treatment of comorbidities and pharmacological agents. The first choice agents are dopaminergic drugs, second choice are gabapentine or oxycodone, and the third choice are clonazepan or slow release valproic acid.

Síndrome de piernas inquietas: intervenciones terapéuticas efectivas / Restless legs syndrome: effective therapeutic interventions

Frente a un paciente que consulta por síntomas compatibles con el síndrome de piernas inquietas, la autora del presenteartículo revisa brevemente sus criterios diagnósticos así como la disponibilidad de tratamientos farmacológicosbasados en la evidencia. Asimismo, se evalúa la relación de este síndrome con los trastornos del sueño. La mayorevidencia hasta el momento la poseen el ropinirol y la pergolida. También se describe junto a otra evidencia deensayos clínicos aleatorizados de la L-dopa, la carbamazepina, la gabapentina, el hierro, la carbegolina. Poca evidenciasustenta el uso del clonazepam,u otras drogas como la rotigotina, hidroquinona, oxicodona y bromocriptina. Sinembargo, la evidencia para todos los tratamientos disponibles hoy para el SPI es de una manera u otra, algo limitada.

Treatment of restless legs syndrome

OBJECTIVE: Restless legs syndrome is a neurological disorder characterized by a desire to move limbs, which is usually only present or worsens during rest or at night. The objective of this article was to review the available literature about pharmacological treatment for this disorder. METHOD: A search of recent literature was undertaken on online databases (Medline, Pubmed, Scielo and Lilacs). RESULTS: 502 articles were retrieved, of which 30 were selected. Dopaminergic agents, anticonvulsants, opioids, benzodiazepines, zolpidem, entacapone and ketamine were all effective on the restless legs syndrome treatment. One study showed that iron was not effective. CONCLUSIONS: Based on few double-blind, randomized, controlled trials, it seems that the best options to treat restless legs syndrome patients are gabapentin and L-dopa associated to its sustained release formulation.

OBJETIVO: A síndrome das pernas inquietas é um transtorno neurológico caracterizado por um desejo incontrolável de mover os membros, que comumente está somente presente ou piora ao descanso ou à noite. O objetivo do trabalho foi a revisão da literatura disponível sobre o tratamento farmacológico para a síndrome das pernas inquietas. MÉTODO: Pesquisa da literatura recente realizada em bases de dados eletrônicas (Medline, Pubmed, Scielo e Lilacs). RESULTADOS: Quinhentos e dois artigos foram encontrados, dos quais 30 foram selecionados. Os agentes dopaminérgicos, os anticonvulsantes, os opióides, os benzodiazepínicos, o zolpidem, o entacapone e a ketamina foram eficazes no tratamento da síndrome das pernas inquietas. Um estudo mostrou que o ferro não foi eficaz. CONCLUSÕES: Baseado nos poucos estudos duplo-cegos, randomizados e controlados, parece que as melhores opções para tratar os pacientes com síndrome das pernas inquietas são a gabapentina e L-dopa associada à sua formulação de liberação lenta.

Síndrome de piernas inquietas / Syndrome of disturb legs

El Síndrome de las Piernas Inquietas (SPI) es un síndrome sensitivo motor que se caracteriza por presentar una sensación desagradable en los miembros inferiores que generan la necesidad de mover las extremidades, cediendo o atenuándose los síntomas con el movimiento. En general aparece y/o empeora por la noche y en los momentos de reposo. Es frecuente en la población general, usualmente subconsultado y subdiagnosticado a pesar que altera la calidad de vida del paciente. Se describe el SPI primario de etiología idiomática, de frecuente agregación familiar, y el secundario a deficiencia de hierro, embarazo, enfermedad renal avanzada y patología raquimedular. El diagnóstico es clínico y no requiere complejidad en los estudios complementarios. Se sugiere valorar a los pacientes con un hemograma, dosaje de ferritina, urea, creatinina y glucemia. El tratamiento consiste en tratar la causa secundaria cuando existe, principalmente la deficiencia de hierro. También se sugiere realizar cambios del estilo de vida y tratamiento no farmacológico; en caso de no responder, los agonistas dopaminérgicos, los opioides y los anticonvulsivantes constituyen tratamientos eficaces.

Síndrome de piernas inquietas: actualización clínica / Restless legs syndrome: a clinical update

El síndrome de piernas inquietas (SPI) se caracteriza por una sensación desagradable en las piernas que lleva a la imperiosa necesidad de moverlas, ocurre en reposo y es de preferencia nocturna. Su frecuencia varía entre 2-15 por ciento de la población general adulta y 20-30 por ciento en pacientes urémicos en diálisis. No existe mayor información sobre este cuadro en nuestro medio. Un reciente trabajo nacional da una frecuencia estimativa de 13 por ciento en la población general adulta y 27 por ciento en los pacientes urémicos en diálisis. Objetivo: analizar características clínicas del SPI y recientes avances en su estudio y tratamiento. Se analiza la fisiopatología del síndrome en base a una hipofunción dopaminérgica y las diversas alternativas de sustitución dopaminérgica disponible. En nuestro medio el SPI es tan frecuente como en series internacionales y está subdiagnosticado. Esta revisión enfatiza la necesidad de mayor reconocimiento de esta condición ya que existe terapia farmacológica eficaz