Review Article
Neuroleptic malignant syndrome in children and adolescents: Systematic review of case reportsSíndrome neuroléptico maligno en niños y adolescentes: revisión sistemática de reportes de caso

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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.

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 años. 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) «catatónico», con mutismo (0,912), negativismo (0,825) y flexibilidad cérea (0,522); 2) «extrapiramidal», con alteración de la marcha (0,860), movimientos anormales involuntarios (0,605), rigidez muscular (0,534) y sialorrea (0,430), y 3) «inestabilidad autonómica», 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.

Introduction

The symptoms associated with neuroleptic malignant syndrome (NMS) were first described in 1956 by Ayd, and defined as such by Delay and Deniker in 1968, when they reported an unusual response to haloperidol.1 Initially, the term neuroleptic was used to describe those psychotropic drugs that controlled psychotic symptoms and produced extrapyramidal symptoms as a side effect — in other words, first-generation antipsychotics.2 Thus, NMS was described as a set of signs and symptoms that present as a potentially severe adverse reaction, secondary to the use of first-generation antipsychotics. However, over time it has been seen that it can also occur secondary to the use of atypical antipsychotics, mood stabilisers and even medication other than psychotropic drugs.

Initially, a prevalence of around 0.2%–3% was described in 1993,3 but in recent years a decrease in this has been observed, to 0.01%–0.02%,4 possibly due to greater care in the prescription and titration of medication. Four main symptoms are usually considered for its diagnosis: hyperthermia, muscular rigidity, altered consciousness and autonomic dysfunction. Added to these are diaphoresis, tremors, incontinence, leukocytosis and elevated creatine kinase (CK). Despite this, to date there is no consensus on universal diagnostic criteria.5

Although this adverse reaction can occur at any stage of life, in any gender and in people with both psychiatric and non-psychiatric illness, some risk factors associated with its appearance have been identified, such as advanced age, male gender, polypharmacy, dehydration, malnutrition, rapid administration of antipsychotics, structural brain damage and affective disorders.1, 5 Among the main associated complications are the development of rhabdomyolysis, respiratory failure, kidney failure and sepsis, with a mortality of 5.6%. Among the predictive factors of mortality are advanced age, respiratory, renal and cardiovascular failure.6 It is, then, a widely described and studied syndrome, with various fatal complications. Despite this, there are still few studies in the child–adolescent population. Apparently, it is postulated that the course and treatment in children and adolescents is usually the same as in adults. However, more studies are needed in this regard.1, 2 For this reason, the present work aims to describe the clinical and laboratory characteristics and the treatment of child and adolescent patients with NMS, and we will also analyse the grouping of the symptoms.

Section snippets

Methods

The guidelines of the PRISMA Statement7 guide were followed. A search was carried out in the MEDLINE/PubMed search engine of all the reported cases of NMS from 1 January 2000 to 3 November 2018, entering the terms: (children OR child OR paediatric OR pediatric OR school child OR adolescents OR adolescence OR teenage) AND (case OR report OR case report OR case reports) AND (neuroleptic malignant syndrome). We selected the articles that met the following characteristics: articles written in

Results

The initial search yielded a total of 118 articles. Of these, 59 articles that were not case reports or series were discarded, leaving 59 articles with reports of cases of NMS in children and adolescents published between 1 January 2000 and 3 November 2018.1, 3, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64

From the

Discussion

The current state of knowledge of NMS is based on case reports and series, few of which were carried out in children and adolescents. This study found that more cases were reported in males, similarly to Silva et al.,2 who found a higher frequency of NMS in males (63.63%) in case reports of children and adolescents. This is probably due to this population being more frequently exposed to antipsychotics, since many of the diseases in child and adolescent psychiatry predominantly affect males.65

Conclusions

NMS in this sample was more frequent in males. The most frequently reported symptoms were: muscle rigidity, autonomic instability and fever. According to the factor analysis of symptoms, NMS could be of three types: catatonic, extrapyramidal and autonomically unstable.

Funding

Self-financed.

Conflicts of interest

The authors have no conflicts of interest to declare.

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    Please cite this article as: León-Amenero D, Huarcaya-Victoria J. Síndrome neuroléptico maligno en niños y adolescentes: revisión sistemática de reportes de caso. Rev Colomb Psiquiat. 2021;50:290–300.

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