Síndrome neuroléptico maligno

El síndrome neuroléptico maligno (SNM) es una reacción adversa medicamentosa potencialmente fatal asociada comúnmente a medicamentos antipsicóticos. Este artículo presenta una revisión actualizada sobre el SNM, aborda su epidemiología, factores de riesgo, presentación clínica, posibles mecanismos subyacentes y tratamiento. Se busca mejorar el reconocimiento temprano, diagnóstico y manejo del SNM en el ámbito clínico para reducir su morbimortalidad. La búsqueda de literatura se realizó en PubMed, fueron priorizados ensayos aleatorizados, revisiones sistemáticas, estudios retrospectivos y reportes de caso. La incidencia del SNM ha disminuido en los últimos años, posiblemente debido a una mejor prescripción y titulación de la medicación. Los factores de riesgo incluyen el uso de antipsicóticos de alta potencia, dosis elevadas, incremento rápido de la dosis y uso de antipsicóticos inyectables de depósito. Se han identificado factores ambientales como la deshidratación, sujeción mecánica y temperaturas extremas. Algunas características psicopatológicas, como la agitación psicomotriz y la confusión, también se han asociado al SNM. Los factores hereditarios y los polimorfismos genéticos pueden influir en la susceptibilidad al SNM, pero se requieren estudios adicionales. La fisiopatología del SNM se relaciona con el bloqueo excesivo de los receptores dopaminérgicos, pero otros cofactores y sistemas neurotransmisores también podrían estar involucrados. El cuadro clínico del SNM se caracteriza por cambios en el estado mental, rigidez muscular, hipertermia, síntomas catatónicos y sudoración profusa. Existen diversas formas de tratamiento, desde medidas generales hasta intervenciones farmacológicas.

The Neuroleptic malignant syndrome (NMS) is a potentially fatal adverse drug reaction commonly associated with antipsychotic medications. This article presents an updated review of NMS, addressing its epidemiology, risk factors, clinical presentation, possible underlying mechanisms, and treatment. The aim is to improve early recognition, diagnosis, and management of NMS in the Peruvian clinical setting to reduce morbidity and mortality. The literature search was conducted in PubMed, prioritizing randomized studies, systematic reviews, retrospective studies, and case reports. The incidence of NMS has decreased in recent years, possibly due to better medication prescription and titration. Risk factors include the use of high-potency antipsychotics, high doses, rapid dose escalation, and the use of depot injectable antipsychotics. Environmental factors such as dehydration, mechanical restraint, and extreme temperatures have been identified. Some psychopathological characteristics, such as psychomotor agitation and confusion, have also been associated with NMS. Genetic factors and genetic polymorphisms may influence susceptibility to NMS, but further studies are needed. The pathophysiology of NMS is related to excessive blockade of dopaminergic receptors, but other cofactors and neurotransmitter systems may be involved. The clinical presentation of NMS is characterized by changes in mental status, muscle rigidity, hyperthermia, catatonic symptoms, and profuse sweating. There are various treatment approaches ranging from general measures to pharmacological interventions.

La terapia electroconvulsiva en el síndrome neuroléptico maligno / Electroconvulsive therapy in neuroleptic malignant syndrome

Resumen: Uno de los efectos adversos más importantes de los neurolépticos es la posibilidad de desencadenar el síndrome neuroléptico maligno (NMS). El diagnóstico se determina por exclusión y el manejo terapéutico inicial será retirado por neurolépticos por la administración de benzodiacepinas y, en casos extremos, el uso de la terapia electroconvulsiva (ECT). La ECT es una opción terapéutica eficaz en estos pacientes y en esos casos se obtiene una mala respuesta a la administración con fármacos antipsicóticos. Basándonos en el caso del artículo «Rocuronium-sugammadex for electroconvulsive therapy management in neuroleptic malignant síndrome. A case report¼ donde se describe el manejo exitoso del uso de relajantes no despolarizantes y su reversor específico en terapias electroconvulsivas en pacientes diagnosticados de síndrome neuroléptico maligno, comentamos la fisiopatología e implicaciones anestésicas además de similitudes con otras entidades hipertérmicas, como es la hipertermia maligna.

Abstract: One of the most important adverse effects of neuroleptics is the possibility of triggering neuroleptic malignant syndrome (NMS). The diagnosis is determined by exclusion and the initial therapeutic management will be withdrawn by neuroleptics by the administration of benzodiazepines and, in extreme cases, the use of electroconvulsive therapy (ECT). ECT is an effective therapeutic option in these patients and in these cases a poor response to administration with antipsychotic drugs is obtained. Based on the case of the article «Rocuronium-sugammadex for the management of electroconvulsive therapy in neuroleptic malignant syndrome. A case report¼ where the successful management of the use of non-depolarizing relaxants and their specific reversal in electroconvulsive therapies in patients diagnosed with of malignant neuroleptic syndrome, we comment on the pathophysiology and anesthetic images as well as similarities with other hyperthermic entities, such as malignant hyperthermia.

Síndrome neuroléptico maligno asociado a antipsicóticos atípicos: a propósito de un caso

Introducción: El síndrome neuroléptico maligno (SNM) es infrecuente, con una incidencia del 0,01 al 3,23%, y tiene relación con el consumo de fármacos que interfieren con la dopamina; genera hipertermia, rigidez muscular, confusión, inestabilidad autonómica y la muerte. Caso clínico: Un varón de 35 arios, con antecedentes de catatonía, epilepsia refractaria y deterioro funcional, en tratamiento anticonvulsivo y antipsicótico, requirió cambio frecuente por efectos adversos de este. En julio de 2019 se cambió la clozapina por amisulprida; en septiembre se inicia un cuadro de 2 semanas de fiebre, rigidez muscular, estupor, diaforesis y taquipnea; los paraclínicos mostraron aumento de la creatininasa (CK) y leucocitosis, por lo que se consideró SNM. Se retiró el antipsicótico y se trató con bromocriptina y biperideno, que obtuvieron buena respuesta. A los 10 días del egreso, se inició tratamiento con olanzapina, que generó en diciembre un cuadro clínico similar al descrito, con posterior tratamiento y resolución. Discusión: El diagnóstico se basa en la toma de fármacos que alteren la dopamina, más alteración del estado de conciencia, fiebre e inestabilidad autonómica, junto con paraclínicos como leucocitosis y elevación de la CK. Se debe descartar diagnósticos diferenciales. El diagnóstico temprano generalmente lleva a la remisión total; algunos tendrán complicaciones, secuelas a largo plazo o recidivas. La recurrencia en este caso derivó de la reintroducción temprana del neuroléptico después del primer episodio. El tratamiento se debe individualizar según la gravedad para evitar la muerte. Conclusiones: Rara vez se sospecha que los antipsicóticos atípicos generen SNM; a su vez se debe tener en cuenta el tiempo a la reintroducción después de un episodio.

Introduction: Neuroleptic malignant syndrome (NMS) is uncommon, with an incidence of 0.01% to 3.23%, and is associated with the use of drugs that intervene with dopamine, causing hyperthermia, muscular rigidity, confusion, autonomic instability and death. Case report: A 35-year-old man with a history of catatonia, refractory epilepsy and functional impairment, required frequent changes in his anticonvulsant and antipsychotic treatment, due to adverse effects. During 2019, in the month of July, clozapine was changed to amisul-pride, in September he developed fever, muscle stiffness, stupor, diaphoresis and tachypnea over a two-week period; paraclinical tests showed elevated creatine phosphokinase (CPK) and leukocytosis, so NMS was considered. The antipsychotic was withdrawn and he was treated with bromocriptine and biperiden, with a good response. Ten days after discharge, he began treatment with olanzapine, which generated a similar episode to the one described in December, with subsequent management and resolution. Discussion: The diagnosis is based on the use of drugs that alter dopamine levels, plus altered state of consciousness, fever, autonomic instability and paraclinical tests showing leukocy-tosis and elevated CPK. Differential diagnosis must be ruled out. Early diagnosis generally leads to total remission, although some patients will suffer complications, long-term sequelae or recurrences. The recurrence in this case derived from the early reintroduction of the neuroleptic after the first episode. Treatment should be individualised according to severity to avoid mortality. Conclusions: Atypical antipsychotics are rarely suspected of generating NMS. Moreover, the time to reintroduction after an episode must also be taken into account.

Sospecha fallida de síndrome neuroléptico maligno en una paciente con esquizofrenia / Failed suspicion of neuroleptic malignant syndrome in a patient with schizophrenia

Introducción: el estado mental alterado es un término general que se utiliza para describir varios trastornos del funcionamiento mental, que pueden variar desde una ligera confusión hasta el coma. En general no es un diagnóstico, por el contrario hace referencia a un grupo de síntomas neurológicos variables e inespecíficos que requieren una mayor determinación de las causas. Dentro de estas se deben considerar en el adulto mayor los efectos adversos e interacciones medicamentosas. Los pacientes con antecedente de esquizofrenia requieren tratamiento de por vida aunque los síntomas desaparezcan, por ello los medicamentos antipsicóticos deben tenerse en cuenta por sus potenciales efectos asociados. El síndrome neuroléptico maligno (SNM) es uno de estos efectos adversos con riesgo de mortalidad. Presentación del caso: se presenta el caso de una paciente de 78 años que ingresó al servicio de urgencias de un hospital de tercer nivel por alteración del estado de conciencia, con antecedentes de esquizofrenia y múltiples comorbilidades, que representan un reto en el abordaje inicial en el servicio de urgencias; los paraclínicos tomados mostraron elevación de la CPK

Introduction: Altered mental status (AMS) is a general term used to describe various disorders that affect mental function. AMS ranges from mild confusion to coma. Normally, it is not a diagnosis, instead it refers to a group of variable and nonspecific neurological symptoms which require further determination of the causes. Drugs adverse effects and interactions must be taken into account in the elderly. Schizophrenia patients require lifelong treatment even if their symptoms disappear, therefore antipsychotic drugs should be considered due to their potential side effects. Neuroleptic malignant syndrome (NMS) is one of these life-threatening adverse reactions. Case presentation: a case is presented in a 78-year-old female patient, with a history of schizophrenia and multiple comorbidities, admitted to a tertiary hospital emergency room for altered consciousness which posed a challenge for the emergency initial approach; laboratory workup revealed elevated CPK levels.

Síndrome neuroléptico maligno en un hospital general

Describimos la presentación clínica y dificultades diagnósticas de un caso de síndrome neuroléptico maligno en un hospital general. El paciente fue un varón de 18 años con diagnóstico de retraso mental grave e historia de convulsiones que recibía tratamiento irregular con risperidona y fenitoína. Tras presentar irritabilidad, agresividad y agitación psicomotriz acude a hospital psiquiátrico en donde le indican incremento de dosis de risperidona. Posteriormente por persistencia de agresividad, acude a hospital psiquiátrico en donde se indicó haloperidol, midazolam y levomepromazina, a los pocos días presentó distonía oro mandibular, alza térmica y distonía generalizada con dificultad para la deglución de alimentos, motivo por el cual acudió a hospital general y fue diagnosticado de síndrome neuroléptico maligno. El paciente recibió tratamiento con bromocriptina y diazepam durante hospitalización y tuvo evolución favorable de síntomas neuropsiquiátricos. El síndrome neuroléptico maligno es un evento adverso raro y fatal. Está asociado al uso de psicotrópicos, especialmente antipsicóticos.

We describe the clinical presentation and diagnostic difficulties of a case of Neuroleptic Malignant Syndrome in a general hospital. The patient was an 18-year-old male with severe mental retardation and a history of seizures who received irregular treatment with risperidone and phenytoin. After presenting irritability, aggressiveness, and psychomotor agitation, he went to a psychiatric hospital where received an increase in the dose of risperidone. Subsequently, due to persistence of aggressiveness, he went to a psychiatric hospital where haloperidol, midazolam and levomepromazine were indicated, after few days developed oromandibular dystonia, temperature rise and generalized dystonia with difficulty swallowing food, which is why he went to hospital general and was diagnosed with Neuroleptic Malignant Syndrome. Patient received treatment with bromocriptine and diazepam during hospitalization with favorable evolution of neuropsychiatric symptoms. Neuroleptic Malignant Syndrome is a rare and fatal adverse event. It is associated with the use of psychotropics, especially antipsychotics.

Síndrome neuroléptico maligno asociado con intoxicación aguda por un organofosforado: reporte de caso / Neuroleptic malignant syndrome associated with acute organophosphate poisoning: Case report

El síndrome neuroléptico maligno es una condición clínica rara y potencialmente letal que frecuentemente se asocia con el uso de antipsicóticos. En la literatura especializada se encontró únicamente un reporte de caso relacionado con la ingestión de organofosforados. Se presenta un paciente con un cuadro clínico correspondiente al síndrome neuroléptico maligno posterior a la ingestión de clorpirifós. Como resultado de un intento de suicidio con el mencionado organofosforado, el hombre de 57 años presentó deterioro agudo del estado de consciencia, evolución neurológica tórpida e inestabilidad autonómica asociada a rigidez e hipertermia persistentes, así como incremento de la creatina-fosfocinasa (creatine phosphokinase, CPK). Se le administró tratamiento con bromocriptina, con lo cual el cuadro clínico remitió, y fue dado de alta sin secuelas. El diagnóstico del síndrome neuroléptico maligno es clínico y debe contemplarse en cualquier caso de exposición a sustancias que puedan resultar en una desregulación de la neurotransmisión dopaminérgica, con el fin de iniciar el tratamiento oportuno y contrarrestar efectivamente los efectos.

Neuroleptic malignant syndrome is a rare and potentially fatal clinical condition frequently associated with the use of antipsychotics. In the literature, there is only one case report associated with the intake of organophosphates. We present the case of a patient who presented with a clinical picture compatible with neuroleptic malignant syndrome, after the ingestion of an organophosphate (chlorpyrifos). A 57-year-old man who consulted for attempted suicide, acute deterioration of consciousness, torpid neurological evolution, and associated autonomic instability associated with rigidity, persistent hyperthermia, and elevated CPK. Bromocriptine treatment was offered, which resolved the clinical picture. The association with the ingestion of an organophosphate was established, and he was discharged without sequelae. The diagnosis of neuroleptic malignant syndrome is clinical and should be considered in any case of exposure to substances that may lead to dysregulation of dopaminergic neurotransmission in order to initiate timely therapy and impact outcomes.

Neuroleptic malignant syndrome in a postoperative patient: A case report.

Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis. A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity. Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms. The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.

Síndrome neuroléptico maligno en paciente postoperada: a propósito de un caso / Neuroleptic malignant syndrome in a postoperative patient: a case report

El síndrome neuroléptico maligno es una emergencia médica poco frecuente asociada al uso de antipsicóticos y otros fármacos antidopaminérgicos. No se dispone de una prueba específica para su diagnóstico, basándose este en una alta sospecha clínica y la realización de un buen diagnóstico diferencial. Un cuadro clínico compatible, destacando la hipertermia, rigidez muscular, alteración del nivel de conciencia y signos de rabdomiolisis en los estudios analíticos, junto con el antecedente de la toma de fármacos neurolépticos, constituyen los elementos clave para la detección de esta entidad. Debido a su escasa incidencia y su potencial mortalidad, es primordial su conocimiento a través de series de casos descritos en la literatura para facilitar su sospecha diagnóstica ante un caso clínico compatible. A continuación, exponemos un caso de una paciente de 79 años con consumo crónico de alcohol como único antecedente de interés, que recibió una dosis única de haloperidol tras un cuadro de delirio en el contexto de un postoperatorio convencional de traumatología. Posteriormente, desarrolló un cuadro de deterioro progresivo del nivel de conciencia, diaforesis, rigidez muscular generalizada, hipertermia, junto a acidosis metabólica severa, hiperlactacidemia, rabdomiolisis, hipertransaminasemia e hipocalcemia. Tras excluir otras entidades compatibles con la clínica, el síndrome neuroléptico maligno se postuló como la principal hipótesis diagnóstica, reforzándose el diagnóstico tras la mejoría clínica y analítica evidente posterior al inicio del tratamiento con dantrolene. La paciente pudo, finalmente, ser dada de alta escasos días después del inicio del cuadro sin presentar secuelas.(AU)

Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis.A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity.Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms.The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.(AU)

Manía transcultural en UCI / Cross-cultural mania in ICU

Objetivo: Presentar el caso clínico de una fase grave de manía que padece un posible síndrome neuroléptico maligno (SNM). Caso clínico joven de 16 años, natural de España, con familia de origen argelina. Diagnosticada de trastorno bipolar. En el episodio actual, inicia un cuadro de descompensación psicopatológica tras el abandono del tratamiento psicofarmacológico. Presenta agripnia, irritabilidad, fugas de domicilio, ánimo expansivo, así como alteraciones del comportamiento rechazando toda práctica de su cultura islámica. Debido a todo ello, precisa un ingreso involuntario en la unidad de hospitalización. Durante este, debido a conductas graves, se requiere contención mecánica y farmacológica. Súbitamente comienza con un cuadro de fiebre, temblor generalizado y aumento de CPK en la analítica, lo que motiva su traslado a UCI para observación y tratamiento intensivo ante la posibilidad de SNM.Resultadostras la estabilización se decide el alta con diagnóstico de posible SNM e infección respiratoria, apreciándose una mejoría clínica evidente.Conclusionesno existen criterios universales para el SNM, la paciente presenta varios síntomas típicos no pudiéndose confirmar que estemos antes un SNM en su totalidad. Los aspectos socio-culturales modulan la psicopatología de una forma característica. (AU)

Objective: To present the clinical case of a severe phase of mania suffering from a possible Neuroleptic Malignant Syndrome (NMS).Clinical case16-year-old girl, native of Spain, family of Algerian background. Diagnosed with bipolar disorder. In the current episode, she begins a psychopathological decompensation after abandoning psychopharmacological treatment. She presents agripnia, irritability, escapes from home, expansive mood, as well as behavioral alterations rejecting any practice of her Islamic culture. Due to all this, she needs an involuntary admission to the hospitalization unit. During this, due to serious behaviors, mechanical and pharmacological restraint is required. Suddenly she begins to develop fever, generalized tremor and increased CPK in blood tests, which led to her transfer to the ICU for observation and intensive treatment due to the possibility of NMS.ResultsAfter stabilization, discharged was decided with a diagnosis of possible NMS and respiratory infection, with evident clinical improvement.ConclusionsThere are no universal criteria for NMS, the patient presents several typical symptoms but it is not possible to confirm that we are before a NMS in its totality. Socio-cultural aspects modulate psychopathology in a characteristic way. (AU)

Síndrome neuroléptico maligno secundario a quetiapina / Neuroleptic malignant syndrome secondary to quetiapine

Objetivo: Describir un caso clínico de una paciente tratada con quetiapina a alta dosis de larga duración en el que produjo una reacción adversa atípica.Descripción del caso clínico: Mujer de 82 años institucionalizada en una residencia para mayores de edad, acude a urgencias con síntomas de fiebre (39º), espasticidad y cambio de estado mental. Se excluyeron los diagnósticos diferenciales iniciales: accidente cerebrovascular e infección, por lo que con los síntomas presentados se diagnosticó de SNM. En el tratamiento farmacológico en el momento del ingreso destacó un dosis de quetiapina 400mg/24h; confirmado con su centro de residencia debido a las discrepancias con su prescripción electrónica. Según informes médicos, la paciente había recibido este tratamiento durante dos meses previo al ingreso, aunque el SNM es un efecto secundario poco común entre los antipsicóticos posee unas consecuencias fatales. El primer día de hospitalización se suspendió la quetiapina y recibió tratamiento específico contra el SNM, compuesto por dantroleno, fluidoterapia y cuidados de apoyo. El SNM se resolvió a los 3 días.Discusión: A pesar de que los antipsicóticos atípicos (AA) se consideren de mayor seguridad debido a su baja potencia para bloquear los receptores D2, pueden causar SNM incluso cuando se prescriben en monoterapia. Por ello, es fundamental un seguimiento de los tratamientos crónicos especialmente en personas mayores con un deterioro cognitivo de base.Esto enfatiza la importancia de la comunicación médico-farmacéutico para promover la seguridad de pacientes y la importancia de las notificaciones. (AU)

Aim: To describe a clinical case of a patient treated with quetiapine at high dose of long duration in which it produced an atypical adverse reaction.Description of the clinical case: An 82-year-old woman institutionalized in a nursing home for the elderly, went to the emergency room with the next symptoms; fever (39º), spasticity and change in mental state. After excluding other pathologies, she was diagnosed NMS. Pharmacological treatment at the time of admission a dose of quetiapine 400mg/24h attracted attention; which was confirmed with her center of residence due to discrepancies with her electronic prescription. According to medical reports, the patient had received this treatment for two months before admission, although NMS is an uncommon side effect among antipsychotics with fatal consequences. Hospitalization first´s day, quetiapine was discontinued and she received specific treatment for NMS, consisting of dantrolene, fluid therapy and supportive care. The NMS was resolved after 3 days.Discussion: Although atypical antipsychotics (AA) are considered safer because of their low potency in blocking D2 receptors, they can cause NMS even when prescribed in monotherapy. Therefore, a follow-up of chronic treatments is essential, especially in older people with a basic cognitive impairment.This case emphasizes the importance of medical-pharmaceutical communication´s to promote patient safety and the importance of reporting. (AU)

Síndrome neuroléptico maligno en niños y adolescentes: revisión sistemática de reportes de caso / Neuroleptic malignant syndrome in children and adolescents: Systematic review of case reports

RESUMEN Introducción: El síndrome neuroléptico maligno (SNM) es una rara y potencialmente fatal reacción adversa medicamentosa. Aún son pocos los estudios de esta entidad en la población infanto-juvenil. Objetivos: Describir las características clínicas, de laboratorio y terapéuticas de los pacientes niños y adolescentes con SNM. Analizar la agrupación de síntomas presentes en el SNM en la misma población. Material y métodos: Se realizó una búsqueda en MEDLINE/PubMed de todos los casos reportados de SNM desde enero del 2000 hasta noviembre del 2018 y se identificaron las variables demográficas, clínicas, laboratoriales y terapéuticas. Se realizó un análisis factorial de los síntomas. Resultados: Se incluyó a 57 pacientes (42 varones y 15 mujeres), con edad promedio de 13,65 ± 3,89 arios. La aparición del SNM ocurrió a los 11,25 ± 20,27 días (con antipsicóticos típicos) y a los 13,69 ± 22,43 días (con antipsicóticos atípicos). Los síntomas más frecuentes fueron la rigidez muscular (84,2%), inestabilidad autonómica (84,2%) y fiebre (78,9). Los hallazgos de laboratorio más frecuentes fueron la elevación del CK y leucocitosis (42.1%). El tratamiento más usado fue la indicación de benzodiacepinas (28,1%). En el análisis factorial exploratorio de los síntomas encontramos 3 factores: 1) «catatónico¼, con mutismo (0,912), negativismo (0,825) y flexibilidad cérea (0,522); 2) «extrapiramidal¼, con alteración de la marcha (0,860), movimientos anormales involuntarios (0,605), rigidez muscular (0,534) y sialorrea (0,430), y 3) «inestabilidad autonómica¼, con fiebre (0,798), alteración de la consciencia (0,795) e inestabilidad autonómica (0,387). Conclusiones: El SNM en niños y adolescentes podría ser de 3 tipos: catatónico, extrapiramidal e inestable autonómico.

ABSTRACT Introduction: Neuroleptic malignant syndrome (NMS) is a rare and potentially fatal drug adverse reaction. There are still few studies of this entity in the child-adolescent population. Objectives: Describe the clinical, laboratory and therapeutic characteristics of children and adolescent patients with NMS. Analyse the grouping of symptoms present in NMS in the same population. Material and methods: A MEDLINE/PubMed search of all reported cases of NMS from January 2000 to November 2018 was performed and demographic, clinical, laboratory and therapeutic variables were identified. A factorial analysis of the symptoms was performed. Results: 57 patients (42 males and 15 females) were included, (mean age 13.65 ± 3.89 years). The onset of NMS occurred at 11.25± 20.27 days with typical antipsychotics and at 13.69 ± 22.43 days with atypical antipsychotics. The most common symptoms were muscle stiffness (84.2%), autonomic instability (84.2%) and fever (78.9). The most common laboratory findings were CPK elevation and leucocytosis (42.1%). The most used treatment was benzodiazepines (28.1%). In the exploratory factorial analysis of the symptoms we found 3 factors: 1) "Catatonic" with mutism (0.912), negativism (0.825) and waxy flexibility (0.522); 2) "Extrapyramidal" with altered gait (0.860), involuntary abnormal movements (0.605), muscle stiffness (0.534) and sialorrhoea (0.430); and 3) "Autonomic instability" with fever (0.798), impaired consciousness (0.795) and autonomic instability (0.387). Conclusions: NMS in children and adolescents could be of 3 types: catatonic, extrapyramidal and autonomic unstable.

Neuroleptic malignant syndrome in children and adolescents: Systematic review of case reports.

INTRODUCTION: Neuroleptic malignant syndrome (NMS) is a rare and potentially fatal drug adverse reaction. There are still few studies of this entity in the child-adolescent population. OBJECTIVES: Describe the clinical, laboratory and therapeutic characteristics of children and adolescent patients with NMS. Analyse the grouping of symptoms present in NMS in the same population. MATERIAL AND METHODS: A MEDLINE/PubMed search of all reported cases of NMS from January 2000 to November 2018 was performed and demographic, clinical, laboratory and therapeutic variables were identified. A factorial analysis of the symptoms was performed. RESULTS: 57 patients (42 males and 15 females) were included, (mean age 13.65 ±â€¯3.89 years). The onset of NMS occurred at 11.25 ±â€¯20.27 days with typical antipsychotics and at 13.69 ±â€¯22.43 days with atypical antipsychotics. The most common symptoms were muscle stiffness (84.2%), autonomic instability (84.2%) and fever (78.9). The most common laboratory findings were CPK elevation and leucocytosis (42.1%). The most used treatment was benzodiazepines (28.1%). In the exploratory factorial analysis of the symptoms we found 3 factors: 1) "Catatonic" with mutism (0.912), negativism (0.825) and waxy flexibility (0.522); 2) "Extrapyramidal" with altered gait (0.860), involuntary abnormal movements (0.605), muscle stiffness (0.534) and sialorrhoea (0.430); and 3) "Autonomic instability" with fever (0.798), impaired consciousness (0.795) and autonomic instability (0.387). CONCLUSIONS: NMS in children and adolescents could be of 3 types: catatonic, extrapyramidal and autonomic unstable.

Neuroleptic malignant syndrome in a postoperative patient: a case report. / Síndrome neuroléptico maligno en paciente postoperada: a propósito de un caso.

Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis. A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity. Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms. The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.

Neuroleptic Malignant Syndrome Associated with Atypical Antipsychotics: A Case Report. / Síndrome neuroléptico maligno asociado a antipsicóticos atípicos: a propósito de un caso.

INTRODUCTION: Neuroleptic malignant syndrome (NMS) is uncommon, with an incidence of 0.01% to 3.23%, and is associated with the use of drugs that intervene with dopamine, causing hyperthermia, muscular rigidity, confusion, autonomic instability and death. CASE REPORT: A 35-year-old man with a history of catatonia, refractory epilepsy and functional impairment, required frequent changes in his anticonvulsant and antipsychotic treatment, due to adverse effects. During 2019, in the month of July, clozapine was changed to amisulpride, in September he developed fever, muscle stiffness, stupor, diaphoresis and tachypnea over a two-week period; paraclinical tests showed elevated creatine phosphokinase (CPK) and leukocytosis, so NMS was considered. The antipsychotic was withdrawn and he was treated with bromocriptine and biperiden, with a good response. Ten days after discharge, he began treatment with olanzapine, which generated a similar episode to the one described in December, with subsequent management and resolution. DISCUSSION: The diagnosis is based on the use of drugs that alter dopamine levels, plus altered state of consciousness, fever, autonomic instability and paraclinical tests showing leukocytosis and elevated CPK. Differential diagnosis must be ruled out. Early diagnosis generally leads to total remission, although some patients will suffer complications, long-term sequelae or recurrences. The recurrence in this case derived from the early reintroduction of the neuroleptic after the first episode. Treatment should be individualised according to severity to avoid mortality. CONCLUSIONS: Atypical antipsychotics are rarely suspected of generating NMS. Moreover, the time to reintroduction after an episode must also be taken into account.

Síndrome neurológico maligno: a propósito de un caso / Malignant neurological syndrome: about a case

RESUMEN Fundamento: los neurolépticos con efecto antipsicótico, son eficaces para controlar los síntomas de la esquizofrenia, delirios y alucinaciones. El síndrome neuroléptico maligno es el efecto adverso más grave ocasionado por los antipsicóticos. Objetivo: presentar un caso inusual de un paciente con diagnóstico de cuadro psicótico que presentó un síndrome neuroléptico maligno ocasionado por los antipsicóticos. Presentación del caso: se ingresa un paciente que escucha voces dentro de su cabeza y el médico lo nota hiperconcentrado además realizaba movimientos estereotipados con dificultades para deambular. Al septimo día de hospitalización comienza con rigidez generalizada, temblor, trastornos del lenguaje y disfagia que se interpreta como un síndrome extrapiramidal de causa medicamentosa, con cifras de creatininfosfoquinasa aumentadas. Se emplea la bromocriptina 2,5 mg cada 12 horas, además de hidratación enérgica, anticoagulación profiláctica con heparina de bajo peso molecular y evaluación periódica de la función respiratoria y renal. Conclusiones: el síndrome neurológico maligno corresponde a una reacción de tipo idiosincrático, producida por cualquier fármaco bloqueador del receptor de la dopamina asociada clásicamente a los fármacos antipsicóticos de alta potencia como haloperidol y flufenazina, como se observó en el caso, por lo que fue necesario identificar los signos prodrómicos de forma precoz y realizar las modificaciones terapéuticas de forma oportuna a fin de prevenir el cuadro grave y restablecer la salud del enfermo con mínimo riesgo.

ABSTRACT Background: neuroleptics with an antipsychotic effect are effective in controlling the symptoms of schizophrenia, delusions and hallucinations. Neuroleptic malignant syndrome is the most serious adverse effect caused by antipsychotics. Objective: to present an unusual case of a patient with a diagnosis of psychotic symptoms who presented a neuroleptic malignant syndrome caused by antipsychotics. Case report: a patient who listens to voices inside his head is admitted and the doctor notes that he was hyperconcentrated and performed stereotyped movements with difficulties in wandering. At the 7th day of hospitalization he begins with generalized rigidity, tremor, language disorders and dysphagia that is interpreted as an extrapyramidal syndrome of drug cause, with increased creatinine phosphokinase (CK) levels. Bromocriptine 2.5 mg every 12 hours is used, in addition to vigorous hydration, prophylactic anticoagulation with low molecular weight heparin and periodic assessment of respiratory and renal function. Conclusions: the malignant neurological syndrome corresponds to an idiosyncratic reaction, produced by any dopamine receptor blocker drug classically associated with high potency antipsychotic drugs such as haloperidol and fluphenazine, as observed in the case presented in the article, so it was necessary to identify the prodromal signs early and make the therapeutic changes in a timely manner in order to prevent the serious condition and restore the health of the patient with minimal risk.

Neuroleptic Malignant Syndrome in Children and Adolescents: Systematic Review of Case Reports. / Síndrome neuroléptico maligno en niños y adolescentes: revisión sistemática de reportes de caso.

INTRODUCTION: Neuroleptic malignant syndrome (NMS) is a rare and potentially fatal drug adverse reaction. There are still few studies of this entity in the child-adolescent population. OBJECTIVES: Describe the clinical, laboratory and therapeutic characteristics of children and adolescent patients with NMS. Analyse the grouping of symptoms present in NMS in the same population. MATERIAL AND METHODS: A MEDLINE/PubMed search of all reported cases of NMS from January 2000 to November 2018 was performed and demographic, clinical, laboratory and therapeutic variables were identified. A factorial analysis of the symptoms was performed. RESULTS: 57 patients (42 males and 15 females) were included, (mean age 13.65±3.89 years). The onset of NMS occurred at 11.25±20.27 days with typical antipsychotics and at 13.69±22.43 days with atypical antipsychotics. The most common symptoms were muscle stiffness (84.2%), autonomic instability (84.2%) and fever (78.9). The most common laboratory findings were CPK elevation and leucocytosis (42.1%). The most used treatment was benzodiazepines (28.1%). In the exploratory factorial analysis of the symptoms we found 3factors: 1) "Catatonic" with mutism (0.912), negativism (0.825) and waxy flexibility (0.522); 2) "Extrapyramidal" with altered gait (0.860), involuntary abnormal movements (0.605), muscle stiffness (0.534) and sialorrhoea (0.430); and 3) "Autonomic instability" with fever (0.798), impaired consciousness (0.795) and autonomic instability (0.387). CONCLUSIONS: NMS in children and adolescents could be of 3types: catatonic, extrapyramidal and autonomic unstable.

Síndrome neuroléptico maligno inducido por risperidona y facilitado por sepsis de origen urinario: clínica y fisiopatología / Malignant neuroleptic syndrome induced by risperidone and facilitated by sepsis of urinary origin: clinical aspects and physiopathology

La risperidona es un antagonista selectivo monoaminérgico, con una elevada afinidad por receptores dopaminérgicos, que puede producir síndrome neuroléptico maligno (SNM), considerado una emergencia médica con alto riesgo de muerte. Tiene una incidencia de hasta el 3% y su mortalidad está entre el 10 y 20%. Se reporta el caso de una paciente de 56 años, que reunía los criterios clínicos del SNM, inducido por el uso de risperidona y facilitado por una sepsis de origen urinario. El tratamiento se condujo con un agente agonista dopaminérgico y cambio del antipsicótico, procedimientos que resultaron en una adecuada evolución clínica. El SNM es una entidad de baja prevalencia, para la cual existen criterios diagnósticos con especificidad y sensibilidad mayor del 90%, por lo que debe diferenciarse claramente de otras patologías. Se discute el mecanismo mediante el cual la infección urinaria facilitaría la ocurrencia de esta enfermedad. El diagnóstico precoz mejora la respuesta al manejo adecuado que se establezca en cada caso.

Risperidone is a selective monoaminergic antagonist with a high affinity for dopamine receptors that can cause neuroleptic malignant syndrome (NMS), considered a life-threatening medical emergency. It has an incidence of up to 3% and its mortality is between 10 and 20%. The case of a 56-year-old female who met the clinical criteria of NMS, induced by the use of risperidone and facilitated by a sepsis of urinary origin, is reported. It was managed with a dopamine agonist and the change of antipsychotic, which resulted in a favorable clinical course. The NMS is a low-prevalence entity whose diagnosis has specificity and sensitivity greater than 90%, reason for which must be clearly differentiated from other pathologies. The mechanism by which urinary infection could facilitate the occurrence of this disease is discussed. Early diagnosis improves the response to an adequate management to be established in each case.

Síndrome neuroléptico maligno debido a ziprasidona: reporte de un caso / Neuroleptic malignant syndrome due to ziprasidone: a case report

El síndrome neuroléptico maligno es una rara y potencialmente fatal reacción adversa medicamentosa, asociada usualmente al uso de antipsicóticos. Tiene por características la presencia de fiebre, rigidez muscular, estado mental alterado y disfunción autonómica. Los hallazgos de laboratorio son inespecíficos, sin embargo, la presencia de leucocitosis y elevación de la creatina fosfoquinasason hallazgos frecuentes. Presentamos el caso de un paciente varón de 51 años, natural de Lima con antecedentes médicos de tuberculosis pulmonar y esquizofrenia que acude a nuestro hospital con un cuadro de psicosis quien, luego de ser tratado con ziprasidona administrada por vía intramuscular, presentó los síntomas característicos de un síndrome neuroléptico maligno. Conocer la clínica y la fisiopatología de este síndrome nos permitirá un mejor abordaje, ya que por su poca frecuencia podría no llegar a plantearse dentro de los diagnósticos diferenciales, lo que resultaría perjudicial para el paciente.

Neuroleptic malignant syndrome is a rare and potentially fatal drug adverse reaction, usually associated with antipsychotics. Signs and symptoms include: fever, muscle rigidity, altered mental status and autonomic dysfunction. Laboratory findings are nonspecific, however the presence of leukocytosis and elevated creatinine phosphokinase are frequent findings. We present the case of a 51-year-old male patient from Lima with a medical history of pulmonary tuberculosis and schizophrenia that comes to our hospital with psychotic symptoms. After being treated with ziprasidone, administered by intramuscular injection presents with typical symptoms of neuroleptic malignant syndrome. Knowing the clinical features and the pathophysiology of this syndrome will allow us to better approach the condition. Due to its infrequent presentation, it may not be considered within the differential diagnosis, which could be harmful to the patient.

Síndrome neuroléptico maligno con mielinolisis central pontina / Neuroleptic malignant syndrome with central pontine myelinolysis

RESUMEN El síndrome neuroléptico maligno (SNM) es una complicación severa de los antipsicóticos, en especial los de primera generación como el haloperidol, que fue el primero en el que se describió esta patología, caracterizada por fiebre, rigidez, alteración del estado de conciencia y disautonomías. Por otro lado, la mielinólisis central pontina (ahora llamada síndrome de desmielinización osmótica) resulta de las alteraciones agudas séricas del sodio, como las que ocurren en las reposiciones de hiponatremia, y podría poner en riesgo la vida al igual que el SNM. La asociación de estas dos patologías es inusual y hasta el momento no se conoce con claridad su relación causal, producto de los pocos casos reportados. Aunque se conoce la mortalidad del síndrome neuroléptico maligno, la compañía de la mielinolisis central pontina podría aumentar la morbimortalidad de esta entidad, por lo cual es necesario reconocerla rápidamente para prevenir la aparición de complicaciones, ya que no cuenta con un tratamiento específico. Presentamos el caso de un paciente joven que cursó con estas dos patologías, y consideramos que la causa de la mielinolisis central pontina fue el haloperidol, así como del SNM. A pesar de ello, este medicamento continúa siendo muy seguro en la práctica clínica ya que la aparición de estas complicaciones es una reacción idiosincrática por algún tipo de susceptibilidad genética desconocida.

SUMMARY Neuroleptic malignant syndrome (NMS) is a severe complication of antipsychotics, especially those of first generation such as haloperidol, which was the first in which this pathology was described, characterized by: fever, rigidity, alteration of the state of consciousness and dysautonomies. On the other side, central pontine myelinolysis (Now Called Osmotic Demyelination Syndrome), search results of acute sodium alterations of sodium, as those occurring in hyponatremia replenings and could put life at risk just like the NMS. The association of these two pathologies is unusual and until now, their causal relationship, the result of the few cases reported, is not clearly known. Although the relationship of the neurological syndrome may be limited, the company of central myelolysis could increase the morbidity of this entity, so it is necessary to be required quickly to prevent the onset of complications, which does not have a specific treatment. We present the case of a young patient who has these pathologies and we consider that the cause of centralized myelinolysis is haloperidol as well as NMS, despite this, this medication continues to be very safe in clinical practice since the appearance of These complications is an idiosyncratic reaction due to some type of unknown genetic susceptibility.

Síndrome neuroléptico maligno like

RESUMEN El síndrome neuroléptico maligno like o crisis acinética es una rara y potencialmente letal complicación del abandono de medicación de los pacientes con enfermedad de Parkinson. Se presenta el caso clínico de un paciente de sexo masculino de 52 años de edad, con antecedente de enfermedad de Parkinson de 10 años de evolución que se encuentra en tratamiento con levodopa-carbidopa. Acude a consultar por disminución del estado de conciencia y rigidez muscular generalizada, relacionado con el abandono de medicación 7 días antes del inicio de los síntomas.

ABSTRACT Neuroleptic malignant-like syndrome or akinetic crisis is a rare and potentially lethal complication of the withdrawal of medication of patients with Parkinson's disease. We present the clinical case of 52-year man with 10-year history of Parkinson's disease who is being treated with levodopa-carbidopa. He consults for decreased level of consciousness and general muscular rigidity, related to the withdrawal of the medication 7 days before the onset of symptoms.