Rapid versus slow withdrawal of antiepileptic drugs.

BACKGROUND: The ideal objective of treating a person with epilepsy is to induce remission (free of seizures for some time) using antiepileptic drugs (AEDs) and withdraw the AEDs without causing seizure recurrence. Prolonged usage of AEDs may have long-term adverse effects. Hence, when a person with epilepsy is in remission, it is logical to attempt to discontinue the medication. The timing of withdrawal and the mode of withdrawal arise while contemplating withdrawal of AEDs. This review examines the evidence for the rate of withdrawal of AEDs (whether rapid or slow tapering) and its effect on seizure recurrence. This is an updated version of the Cochrane Review previously published in 2020. OBJECTIVES: To quantify risk of seizure recurrence after rapid (tapering period of three months or less) or slow (tapering period of more than three months) discontinuation of antiepileptic drugs in adults and children with epilepsy who are in remission, and to assess which variables modify the risk of seizure recurrence. SEARCH METHODS: For the latest update, on 8 November 2021, we searched: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid), and SCOPUS. There were no language restrictions. CRS Web includes randomized or quasi-randomized, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), CENTRAL, and the Specialized Registers of Cochrane Review Groups including Epilepsy. SELECTION CRITERIA: Randomized controlled trials that evaluated withdrawal of AEDs in a rapid or slow tapering after varying periods of seizure control in people with epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the trials for inclusion and extracted the data. The outcomes assessed included seizure freedom after one, two, or five years of AED withdrawal; time to recurrence of seizure following withdrawal; occurrence of status epilepticus; mortality; morbidity due to seizure, such as injuries, fractures, and aspiration pneumonia; and quality of life (assessed by validated scale). MAIN RESULTS: There are two included studies in this review. One study randomized 57 children with epilepsy with seizure freedom for at least two years to taper down the AED over one or six months. The study was not blinded and there were no details of randomization. Over the period of 54 months of follow-up, 20/30 participants in the one-month group remained seizure-free compared to 15/27 participants in the six-month group (no evidence of a difference). There was no information on time of seizure recurrence for each group to allow a comparison. The other study involved 149 children. There was a non-significant trend towards a lower risk of seizure recurrence after one year of AED withdrawal in participants allocated to slow tapering (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.58 to 1.01; P = 0.06; very low-certainty evidence). At the end of two years, 30 participants were seizure free in the rapid-tapering group and 29 participants in the slow-tapering group (RR 0.87, 95% CI 0.58 to 1.29; P = 0.48; very low-certainty evidence). At the end of five years, 10 participants were seizure free in the rapid-tapering group and six participants in the slow-tapering group (RR 1.40, 95% CI 0.54 to 3.65; P = 0.49; very low-certainty evidence). There were no data for the other outcomes. Due to the methodological heterogeneity and the difference in the duration of tapering, we did not perform a quantitative synthesis of these studies. Currently, one Italian trial is ongoing that is investigating if a slow or a rapid withdrawal schedule of AEDs influences return of seizures (relapse) in adults with focal or generalized epilepsy who have been seizure free for at least two years (no preliminary results available). AUTHORS' CONCLUSIONS: In view of methodological deficiencies, and small sample size of the two included studies, we cannot draw any reliable conclusions regarding the optimal rate of tapering of AEDs. Using GRADE, we assessed the certainty of the evidence as very low for outcomes for which data were available. We judged both studies to be at an overall high risk of bias. Further studies are needed in adults and children to investigate the optimal rate of withdrawal of AEDs and to study the effects of variables such as seizure types, aetiology, intellectual disability, electroencephalography abnormalities, presence of neurological deficits, and other comorbidities on the rate of tapering.

Phase II/III placebo-controlled randomized trial of safety and efficacy of growth hormone treatment in incomplete chronic traumatic spinal cord injury.

STUDY DESIGN: This is a double blind phase II/III placebo-controlled randomized trial of the safety and efficacy of GH treatment in incomplete chronic traumatic spinal cord injury. OBJECTIVE: The aim of this study was to investigate the possibility to use exogenous GH administration for motor recovery in chronic traumatic incomplete human SCI. The objectives were to establish safety and efficacy of a combined treatment of subcutaneous GH (or placebo) and rehabilitation in this population. SETTING: Hospital Nacional de Parapléjicos METHODS: The pharmacological treatment was a subcutaneous daily dose of growth hormone (GH, Genotonorm 0.4 mg, Pfizer Pharmaceuticals) or placebo for one year. The pharmacological treatment was performed, during the first six months under hospitalization and supervised rehabilitation. RESULTS: The main findings were that the combined treatment of GH plus rehabilitation treatment is feasible and safe, and that GH but not placebo increases the ISNCSCI motor score. On the other hand, the motor-score increment was marginal (after one-year combined treatment, the mean increment of the motor-score was around 2.5 points). Moreover, we found that intensive and long-lasting rehabilitation program per se increases the functional outcome of SCI individuals (measured using SCIM III and WISCI II). CONCLUSIONS: It is important to highlight that our aim was to propose GH as a possible treatment to improve motor functions in incomplete SCI individuals. At least with the doses we used, we think that the therapeutic effects of this approach are not clinically relevant in most subjects with SCI.

Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: Experience from a national multicenter registry.

OBJECTIVE: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). METHODS: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. RESULTS: A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1-57) with a median dose of 4 mg (range = 2-10). The retention rates at 3, 6, and 12 months and last follow-up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log-rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3-26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure-free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow-up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1-8.33, P = .046). SIGNIFICANCE: PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.

Rapid versus slow withdrawal of antiepileptic drugs.

BACKGROUND: The ideal objective of treating a person with epilepsy is to induce remission (free of seizures for some time) using antiepileptic drugs (AEDs) and withdraw the AEDs without causing seizure recurrence. Prolonged usage of AEDs may have long-term adverse effects. Hence, when a person with epilepsy is in remission, it is logical to attempt to discontinue the medication. The timing of withdrawal and the mode of withdrawal arise while contemplating withdrawal of AEDs. This review examines the evidence for the rate of withdrawal of AEDs (whether rapid or slow tapering) and its effect on seizure recurrence. This is an updated version of the original Cochrane Review published in 2006, Issue 2. OBJECTIVES: To quantify risk of seizure recurrence after rapid (tapering period of three months or less) or slow (tapering period of more than three months) discontinuation of antiepileptic drugs in adults and children with epilepsy who are in remission, and to assess which variables modify the risk of seizure recurrence. SEARCH METHODS: For the latest update, on 9 April 2019, we searched: Cochrane Register of Studies (CRS Web, which includes the Cochrane Epilepsy Group Specialized Register, CENTRAL, and ClinicalTrials.gov), MEDLINE (Ovid; 8 April 2019), the WHO International Clinical Trials Registry Platform, and SCOPUS. There were no language restrictions. SELECTION CRITERIA: Randomized controlled trials that evaluate withdrawal of AEDs in a rapid or slow tapering after varying periods of seizure control in people with epilepsy. DATA COLLECTION AND ANALYSIS: Review authors independently assessed the trials for inclusion and extracted the data. The outcomes assessed included seizure freedom after one, two, or five years of AED withdrawal; time to recurrence of seizure following withdrawal; occurrence of status epilepticus; mortality; morbidity due to seizure, such as injuries, fractures, and aspiration pneumonia; and quality of life (assessed by validated scale). MAIN RESULTS: In this review update, we have included one new study. The new study randomized 57 children with epilepsy with seizure freedom for at least two years to taper the AED during over one or six months. The study was not blinded and there were no details of randomization. Over the period of 54 months of follow-up, 20/30 participants in the one-month group remained seizure-free compared to 15/27 participants in the six-month group (no evidence of a difference). There was no information on time of seizure recurrence for each group to allow a comparison. One trial had already been included in the previous version of the review; it involved 149 children. There was a non-significant trend toward a lower risk of seizure recurrence after one year of AED withdrawal in participants allocated to slow tapering (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.58 to 1.01; P= 0.06; very low-certainty evidence). At the end of two years, 30 participants were seizure free in the rapid-tapering group and 29 participants in the slow-tapering group (RR 0.87, 95% CI 0.58 to 1.29; P = 0.48; very low-certainty evidence). At the end of five years, 10 participants were seizure free in the rapid-tapering group and six participants in the slow-tapering group (RR 1.40, 95% CI 0.54 to 3.65; P = 0.49; very low-certainty evidence). There were no data for the other outcomes. Due to the methodological heterogeneity and the difference in the duration of tapering we did not perform a quantitative synthesis of these studies. AUTHORS' CONCLUSIONS: Since the last version of this review was published, we found one new pediatric study. In view of methodological deficiencies, and small sample size of the two included studies, we cannot draw any reliable conclusions regarding the optimal rate of tapering of AEDs. Using GRADE, we assessed the certainty of the evidence as very low for outcomes for which data were available. We judged both studies to be at high risk of bias. Further studies are needed in adults and children to investigate the optimal rate of withdrawal of AEDs and to study the effects of variables such as seizure types, etiology, mental retardation, electroencephalography abnormalities, presence of neurologic deficits, and other comorbidities on the rate of tapering.

CONTEXTE: L'objectif idéal du traitement d'une personne épileptique est d'induire une rémission (absence de crises pendant un certain temps) en utilisant des médicaments antiépileptiques (MAE) et d'arrêter les MAE sans provoquer de récidive des crises. L'utilisation prolongée des MAE pourrait avoir des effets indésirables à long terme. Par conséquent, lorsqu'une personne épileptique est en rémission, il est logique de tenter d'interrompre la médication. La question du moment et du mode d'arrêt se posent lorsque l'on envisage l'arrêt des MAE. Cette revue examine les données probantes sur le taux d'arrêt des MAE (qu'il s'agisse d'un arrêt rapide ou lent) et son effet sur la récurrence des crises. Ceci est une version mise à jour de la revue Cochrane originale publiée en 2006, numéro 2. OBJECTIFS: Quantifier le risque de récidive des crises après un arrêt rapide (période de diminution progressive de trois mois ou moins) ou lent (période de diminution progressive de plus de trois mois) des médicaments antiépileptiques chez les adultes et les enfants épileptiques en rémission, et évaluer les variables qui modifient le risque de récidive des crises. STRATÉGIE DE RECHERCHE DOCUMENTAIRE: Pour la dernière mise à jour, le 9 avril 2019, nous avons fait des recherches dans : le registre Cochrane des études cliniques (CRS Web, qui comprend le registre spécialisé du groupe Cochrane sur l'épilepsie, CENTRAL, et ClinicalTrials.gov), MEDLINE (Ovid ; 8 avril 2019), le système d'enregistrement international des essais cliniques (ICTRP) de l'OMS et SCOPUS. Aucune restriction de langue n'a été appliquée. CRITÈRES DE SÉLECTION: Essais contrôlés randomisés qui évaluent l'arrêt des MAE, par une diminution rapide ou lente, après diverses périodes de contrôle des crises chez les personnes épileptiques. RECUEIL ET ANALYSE DES DONNÉES: Les auteurs de l'étude ont, de manière indépendante, évalué les essais pour l'inclusion et ont extrait les données. Les critères de jugement évalués comprenaient l'absence de crise après un, deux ou cinq ans d'arrêt des MAE ; le délai sans récidive de crise après arrêt ; l'apparition d'un état de mal épileptique ; la mortalité ; la morbidité due à la crise, comme les blessures, les fractures et la pneumonie d'aspiration ; et la qualité de vie (évaluée par une échelle validée). RÉSULTATS PRINCIPAUX: Dans cette mise à jour de la revue, nous avons inclus une nouvelle étude. La nouvelle étude a randomisé 57 enfants souffrant d'épilepsie et ne souffrant pas de crises depuis au moins deux ans afin de réduire la prise des MAE pendant au moins un à six mois. L'étude n'a pas été réalisée en aveugle et il n'y a pas eu de détails sur la randomisation. Au cours de la période de suivi de 54 mois, 20/30 participants du groupe un mois sont restés sans crise d'épilepsie, contre 15/27 participants du groupe six mois (pas de preuve de différence). Il n'y avait pas d'information sur le moment de la récidive des crises dans chaque groupe afin de permettre une comparaison. Un essai avait déjà été inclus dans la version précédente de la revue ; il concernait 149 enfants. Nous avons constaté une tendance non­significative de diminution du risque de récidive des crises après un an d'arrêt des MAE, chez les participants affectés à la diminution lente (rapport de risque (RR) 0,76, intervalle de confiance (IC) à 95% 0,58 à 1,01 ; P= 0,06 ; données probantes de très faible certitude). Au bout de deux ans, 30 participants étaient exempts de crises dans le groupe à diminution rapide et 29 participants dans le groupe à diminution lente (RR 0,87, 95 % IC 0,58 à 1,29 ; P = 0,48 ; données probantes de très faible certitude). Au bout de cinq ans, dix participants étaient exempts de crises d'épilepsie dans le groupe à diminution rapide et six dans le groupe à diminution lente (RR 1,40, IC 95% 0,54 à 3,65 ; P = 0,49 ; données probantes de très faible certitude). Il n'y avait pas de données sur les autres critères de jugement. En raison de l'hétérogénéité méthodologique et de différence dans la durée de la diminution, nous n'avons pas effectué de synthèse quantitative de ces études. CONCLUSIONS DES AUTEURS: Depuis la publication de la dernière version de cette revue, nous avons trouvé une nouvelle étude pédiatrique. Compte tenu des lacunes méthodologiques et de la petite taille de l'échantillon des deux études incluses, nous ne pouvons pas tirer de conclusions fiables concernant le rythme de diminution optimal des MAE. En utilisant GRADE, nous avons évalué la certitude des données probantes comme étant très faible pour les résultats pour lesquels des données étaient disponibles. Nous avons jugé que les deux études présentaient un risque de biais élevé. D'autres études sont nécessaires chez les adultes et les enfants pour étudier le taux d'arrêt optimal des MAE et pour étudier les effets de variables telles que les types de crises, l'étiologie, le retard mental, les anomalies sur l'électroencéphalogramme, la présence de déficits neurologiques et d'autres comorbidités sur le rythme de diminution.

[Value of the cutaneous-plantar reflex in the diagnosis of idiopathic carpal tunnel syndrome]. / Valor del reflejo cutáneo palmar en el diagnóstico del sindrome del túnel del carpo idiopático.

INTRODUCTION: Carpal tunnel syndrome (CTS) is the most common of all focal neuropathies. Its diagnosis is based on a neurophysiological study of the thick motor and sensory fibres in patients with a characteristic clinical picture, although sometimes, in mild cases, this study does not detect the abnormalities. The decision was made to evaluate the small-calibre sympathetic fibres by means of cutaneous-plantar reflex (CPR) in patients with different degrees of idiopathic CTS. SUBJECTS AND METHODS: The study involved 54 cases -15 males and 39 females with CTS- and 15 healthy volunteer controls. The cases were divided into three groups: those with only positive clinical features; those with clinical features and alteration of sensory conduction; and those with clinical features, alteration of sensory and motor conduction, and axonal loss. The CPR was obtained by means of the usual technique (which we modified), involving stimulation of the median nerve in the wrist and recording the response in the contralateral hand. Two successive responses were processed with an interval of more than one minute between them. Special attention was paid to controlling the baseline and sweating. A descriptive statistical inference and correlation analysis was performed. RESULTS: A decrease in amplitude of the response was observed in patients with CTS, with shorter latencies in women and a good correlation between the latencies of the first and the second response. No significant differences were observed in the other parameters that were studied. CONCLUSION: Studying the CPR can provide complementary data in the evaluation of CTS.

Respuesta: Pannus reumatoide: una nomenclatura equívoca / Reply: Rheumatoid pannus: an ambiguous nomenclature

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Variabilidad clínica en la neuromielitis óptica: descripción de tres casos / Clinical variability in neuromyelitis optica: three case reports

Introducción. Se presentan tres casos clínicos, valorados en el último año en nuestro centro, diagnosticados de neuromielitis óptica (NMO) con características clínicas heterogéneas. Casos clínicos. Caso 1: mujer de edad media con cinco brotes de mielitis y aumento de la latencia de la P100 en los potenciales evocados visuales. La resonancia magnética cerebral fue normal y los anticuerpos IgG anti-NMO fueron negativos. Caso 2: mujer de 17 años con un cuadro desarrollado en dos meses de neuritis óptica retrobulbar (NOR) en el ojo izquierdo y posteriormente mielitis cervical y NOR en el ojo derecho, con excelente evolución clínica tras el tratamiento inmunosupresor y anticuerpos IgG anti-NMO positivos. Caso 3: mujer de edad avanzada que había sufrido varios años antes tres episodios de mielitis cervicodorsal, y posteriormente presentó otros dos nuevos episodios y una NOR del ojo derecho sin lesiones desmielinizantes en la resonancia magnética cerebral, con anticuerpos IgG anti-NMO negativos. Conclusiones. El concepto de la NMO ha cambiado desde su descripción original hasta la actualidad. Hoy se concibe como un espectro clínico con unos criterios diagnósticos bien definidos, pero heterogéneo en cuanto a las características clínicas, la edad de aparición o la respuesta al tratamiento, como queda reflejado en los casos que se presentan (AU)

Introduction. Three cases of neuromyelitis optica (NMO) admitted in our hospital with a heterogeneous clinical characteristicsare presented. Case reports. Case 1: a middle-aged woman with five acute transverse myelitis episodes and a high latency of the P100 in the visual evoked potentials. The MRI and the NMO antibodies were both negatives. Case 2: a young lady with a two months duration episode of optic neuritis in one eye first, and both myelitis and optic neuritis on the other eye burst secondly, with a very good evolution and positive NMO antibodies. Case 3: a 72 years-old woman with three episodes of acute transverse myelitis. After three years she had two more acute myelitis bursts and finally one optic neuritis, with no lesions in the brain MRI and negative NMO antibodies. Conclusions. The concept of the NMO has changed from its original description. Today it is conceived as a clinical spectrum by a well definite diagnostic criteria, but very heterogeneous as for the clinical characteristics, the outbreak age, or the response to the treatment, since it remains reflected in this three cases (AU)

Efectos adversos neuropsiquiátricos del ziconotide intratecal / Neuropsychiatric side effects of intrathecal ziconotide

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Mielopatía cervical por pannus reumatoide como forma de la artritis reumatoide / Cervical mielopathy by rheumatoid pannusas onset form of rheumatoid arthritis

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Asociación de trastuzumab con mayor incidencia de metástasis cerebrales en pacientes con cáncer de mama HER2 positivo / Trastuzumab’s association with cerebral metastases and meningeal carcinomatosis in a patient with HER2-positive breast cancer

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