Examining the Features of Neuroleptic Malignant Syndrome in Anti-NMDA Receptor Encephalitis: A Case-Control Study.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with antipsychotics is common in the early stages when psychiatric symptoms predominate, and their use has been associated with serious side effects including neuroleptic malignant syndrome (NMS). The observation of an adverse response to antipsychotics, raising the suspicion of NMS, has been included as a criterion for possible autoimmune psychosis. METHODS: This case-control study included patients who received antipsychotics before referral to the National Institute of Neurology and Neurosurgery of Mexico, where they were diagnosed as having definite ANMDARE, and patients with ANMDARE who did not receive antipsychotics before referral. The neurologic and systemic features that are used to measure an adverse response to antipsychotics, raising the suspicion of NMS, were measured in both groups, including akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, and hyperthermia. A logistic regression analysis was used to determine the relationship between the previous use of antipsychotics and the occurrence of NMS-like reactions. RESULTS: A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before being referred to our institution. In this group, thirty-six patients (72%) were initially classified as having an adverse response, raising the suspicion of NMS, with the following features: akinesia (64%), autonomic instability (58%), generalized rigidity (52%), elevated concentrations of creatine phosphokinase (50%), and hyperthermia (14%). Six patients fulfilled the criteria for NMS (12%). The comparison with patients who did not receive antipsychotics before the clinical assessment did not show a significant difference between groups regarding the frequency of akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, or hyperthermia. Among different antipsychotics, only haloperidol was significantly associated with generalized rigidity as compared to patients who did not receive antipsychotics. CONCLUSIONS: Our study supports previous observations about the high frequency of autonomic dysfunction, hyperthermia, tachycardia, rigidity, and elevated creatine phosphokinase levels in patients with anti-NMDAR encephalitis following the administration of antipsychotic medications. Nevertheless, our study does not suggest a causal link between atypical antipsychotics and the onset of these neurological symptoms, as they were equally frequent among the group of patients who did not receive antipsychotic treatment.

When the fever will not stop, stop the pills! A case report.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics and less frequently with atypical or second-generation antipsychotics. The diagnosis relies on both clinical and laboratory criteria, with other organic and psychiatric conditions being ruled out. CASE REPORT: A 39-year-old female patient, who is institutionalized and completely dependent, has a medical history of recurrent urinary infections and colonization by carbapenem-resistant Klebsiella pneumoniae. Her regular medication regimen included sertraline, valproic acid, quetiapine, risperidone, lorazepam, diazepam, haloperidol, baclofen, and fentanyl. The patient began experiencing dyspnea. Upon physical examination, she exhibited hypotension and a diminished vesicular murmur at the right base during pulmonary auscultation. Initially, after hospitalization, she developed high febrile peaks associated with hemodynamic instability, prompting the initiation of antibiotic treatment. Despite this, her fever persisted without an increase in blood inflammatory parameters, and she developed purulent sputum, necessitating antibiotherapy escalation. The seventh day of hospitalization showed no improvement in symptoms, suggesting NNMS as a differential diagnosis. All antipsychotic and sedative drugs, as well as antibiotherapy, were discontinued, after which the patient showed significant clinical improvement. CONCLUSION: Antipsychotic agents are commonly employed to manage behavioral changes linked to various disorders. However, their severe side effects necessitate a high degree of vigilance, the cessation of all medications, and the implementation of supportive care measures. A prompt and accurate diagnosis of NMS is crucial to alleviating the severe, prolonged morbidity and potential mortality associated with this syndrome.

Neuroleptic malignant syndrome in pregnancy: case report and literature review.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a serious complication associated with the use of drugs that affect dopaminergic system neurotransmission. The occurrence of NMS during pregnancy or gestation is considered a life-threatening obstetric emergency. CASE: We are reporting the first case in Latin America of NMS in one pregnant women with acute psychotic episode. One day after starting with antipsychotic therapy, she developed a fever higher than 39.0 °C with tachycardia, tachypnea, generalized muscle rigidity and somnolence, with creatine kinase (CPK) levels evidencing a result of 2800 U/L. She was treated successfully with levetiracetam, biperiden and quetiapine. DISCUSSION: A search in PubMed, Embase and Ovid from 1988 to 2016 resulted in seven cases reported in either pregnant or puerperal women. In general, NMS resolves within 3-14 days; most NMS cases reported during pregnancy have involved the use of haloperidol (5 case reports) which is concordant with this report. The obstetric results were good in cases reported, only two women showed signs, among them: hyperemesis gravidarum and preterm delivery. Most of the pregnant women who had NMS presented other associated comorbidities, being mostly of infectious origin. In other investigations, it has been affirmed that NMS can become lethal in adults; however, in our search for pregnant women with this disease, no associated mortality was found. CONCLUSIONS: NMS is seen infrequently during pregnancy. The clinical diagnosis requires high suspicion by the examiner. It is important that obstetricians timely recognize the condition.

Síndrome Neuroléptico Maligno en el manejo anestésico / Neuleptic Malignant Syndrome in anesthetic management

El Síndrome Neuroléptico Maligno (SNM) es un trastorno de aparición rara en pacientes tratados con fármacos neurolépticos, cuyos efectos secundarios son a menudo extensiones de las muchas acciones farmacológicas de las drogas sobre el Sistema Nervioso Central, Cardiovascular, Sistema Nervioso Autónomo y funciones endocrinas. Sus efectos extrapiramidales incluyen cinco variedades de Síndromes producidos por el uso de las drogas neurolépticas. Tres de ellos aparecen por lo general simultáneamente con la administración de la droga y dos aparecen tardíamente después de un tratamiento prolongado durante meses o años. Su incidencia es aproximadamente 0.2-0.4 por ciento de los pacientes tratados con neurolépticos, siendo mayor en varones con una proporción 2:145. La existencia de un patrón constante de incidencia más elevada en varones que en mujeres es atribuida a la tendencia de los clínicos a instaurar un tratamiento intenso en varones, debido a que son más violentos los varones sicóticos que las mujeres enfermas. Los síntomas en el 68 por ciento de los casos aparecen durante la primera semana de tratamiento neuroléptico. El 80 por ciento de los pacientes son menores de 40 años con una edad mínima de 20-50 años, y aun cuando el adulto joven es el paciente típico, puede aparecer en ancianos y niños que ingieren neuroléptico accidentalmente. Nos propusimos realizar esta revisión bibliográfica para comprender mejor las acciones farmacológicas de estos compuestos, que a pesar de ser indicados con frecuencia en pacientes psicóticos y comprobar por la bibliografía revisada que su aparición no es frecuente, en ocasiones puede ser grave y potencialmente fatal...(AU)

Neuroleptic malignant syndrome-like, or--dopaminergic malignant syndrome--due to levodopa therapy withdrawal. Clinical features in 11 patients.

A clinical picture named neuroleptic malignant-like syndrome has been described in patients with Parkinson's disease (PD) who suddenly stop their L-dopa treatment. The sudden withdrawal of the drug is deemed to lead to an acute deficiency stage in a patient who has an iatrogenic increase of dopaminergic transmission. We present a series of 11 patients with PD with an average age of 72.09 years, a mean disease duration of 9.45 years who developed this problem after a 92.72 h latency period. If patients with PD develop severe rigidity, stupor and hyperthermia, L-dopa withdrawal should be suspected and the dopaminergic drug restarted as soon as possible.

Síndrome Neuroléptico Maligno / Malignant neuroleptic syndrome

El síndrome neuroléptico maligno constituye una complicación infrecuente asociada con el uso de neruolépticos. El cuadro establecido tiene toma de conciencia, rigidez generalizada, disautonomías asociadas con rabdomiólisis con creatinin fosfoquinasa elevada. Se presenta un paciente del sexo masculino de 31 años de edad, con antecedentes de cuadros delirantes alucinatorios a los 7 años, a los 21 y el actual. Los primeros síntomas comenzaron 2 meses antes de su ingreso, con alucinaciones auditivas. Comienza tratamiento con haloperidol; al no mejorar el cuadro psicótico y estar muy agresivo deciden asociarle clorpromazina. Un mes después presenta fiebre y manifestaciones respiratorias. Días después empeora la fiebre, aparece la rigidez axial y la sialorrea. Es trasladado a cuidados intensivos con el diagnóstico de síndrome neuroléptico maligno, comienza tratamiento específico, no obstante fallece a los 3 días. Se concluye que el síndrome neuroléptico maligno es una complicación neurológica infrecuente pero muy grave, con una elevada mortalidad en los casos no tratados de manera precoz

Síndrome neuroléptico maligno en postoperatorio tardío / Neuroleptic malignant syndrome in postoperative period

La aparición de fiebre en el postoperatorio puede señalar una potencial complicación. A veces ésta sólo puede estar originada por drogas, especialmente neurolépticos, como en este caso. Varón 24 años sometido a gran cirugía tóraco-abdominal, por escopetazo con intento suicida. Con evolución favorable se da de alta quirúrgica a los 14 días con Haldol para evaluacion por siquiatra que lo sustituye por Fluanxol. Comenzando una semana después con fiebre alta, taquicardia, hipotermia, sudoración, calofríos y desorientación. Después de descartar cuadro febril de origen quirúrgico se plantea SNM, suspendiéndose neuroléptico e iniciando tratamiento cediendo fiebre en 24 horas. Comentario: A pesar de lo escaso de su presentación se analiza un caso de fiebre por drogas que siempre se debe tener presente en cirugía

Selective destruction of nigrostriatal dopaminergic neurons does not alter [3H]-ryanodine binding in rat striatum.

Dopamine nigrostriatal neurons are important for motor control and may contain a particularly dense population of ryanodine receptors involved in the control of dopamine release. To test this hypothesis, we used a classical model of unilateral selective lesion of these neurons in rats based on 6-hydroxydopamine (6-OHDA) injection into the substantia nigra. Binding of [3H]-GBR 12935, used as a presynaptic marker since it labels specifically the dopamine uptake complex, was dramatically decreased by 83-100% in striatum homogenates after 6-OHDA lesion. On the contrary, no reduction of [3H]-ryanodine binding was observed. The present data indicate that [3H]-ryanodine binding sites present in rat striatum are not preferentially localized in dopaminergic terminals.

Selective destruction of nigrostriatal dopaminergic neurons does not alter [3H]-ryanodine binding in rat striatum

Dopamine nigrostriatal neurons are important for motor control and may contain a particularly dense population of ryanodine receptors involved in the control of dopamine release. To test this hypothesis, we used a classical model of unilateral selective lesion of these neurons in rats based on 6-hydroxydopamine (6-OHDA) injection into the substantia nigra. Binding of [3H]-GBR 12935, used as a presynaptic marker since it labels specifically the dopamine uptake complex, was dramatically decreased by 83-100 percent in striatum homogenates after 6-OHDA lesion. On the contrary, no reduction of [3H]-ryanodine binding was observed. The present data indicate that [3H]-ryanodine binding sites present in rat striatum are not preferentially localized in dopaminergic terminals

Síndrome neuroléptica maligna: relato de caso com recorrência associada ao uso de olanzapina / Neuroleptic malignant syndrome: case report with recurrence associated with the use of olanzapine

A síndrome neuroléptica maligna (SNM) consiste em reaçao idiossincrática a neurolépticos, provavelmente relacionada a bloqueio dos receptores dopaminérgicos nos gânglios da base, sendo por isso também conhecida como síndrome da deficiência aguda de dopamina. A SNM é caracterizada por hiperpirexia, alteraçao do nível de consciência, hipertonia, disfunçao autonômica e insuficiência respiratória, podendo ainda ser encontrados rabdomiólise e leucocitose. O haloperidol é a droga mais frequentemente associada à síndrome. Relatamos o caso de um paciente de 30 anos que apresentou SNM em duas ocasioes diferentes, a primeira delas relacionada ao uso de haloperidol e clorpromazina e a segunda relacionada ao uso de olanzapina, fato este sem mençao anterior na literatura indexada.

[Neuroleptic malignant syndrome: case report with recurrence associated with the use of olanzapine]. / Síndrome neuroléptica maligna. Relato de caso com recorrência associada ao uso de olanzapina.

The neuroleptic malignant syndrome (NMS) consists in an idiosyncratic reaction to neuroleptic drugs, probably related to a blockage of dopamine receptors in basal ganglia. Research criteria for diagnosing NMS from DSM-IV require severe rigidity and fever accompanied by 2 of 10 minor features including diaphoresis, dysphagia, tremor, incontinence, altered mentation, mutism, tachycardia, elevated or labile blood pressure, leukocytosis and elevation of creatine phosphokinase. From a clinical point of view, the NMS may range a large spectrum of presentations. Haloperidol is the most frequent drug associated with this syndrome. We report the case of a 30 year-old man who developed NMS at two different occasions, the first related to haloperidol and chlorpromazine and the second related to olanzapine, to our knowledge without previous mention in the indexed literature.

[Malignant neuroleptic syndrome, medical-psychiatric approach]. / Sindrome neuroléptico maligno, aproximación médico-psiquiátrica.

We report the case of a 42 years old male, with a bipolar disorder and receiving lithium therapy, valproic acid and clonazepam. Due to an exacerbation of his underlying disease, he was admitted to a psychiatric clinic and received 50 mg of intramuscular chlorpromazine in two occasions. Afterwards, the patient had an alteration of consciousness, fever reaching 39 degrees C and generalized muscular rigidity. Laboratory work-up showed a normal brain CT scan, a diffuse slowness in the EEG and a creatinphosphokinase that reached values of 3.040 U/l. He was transferred to an intensive care unit and treated with sodium dantrolene and bromocriptine, obtaining a good clinical response.

Síndrome neuroléptico maligno: aproximación médico-psiquiátrica / Malignant neuroleptic syndrome: a clinical-psychiatric approach

We report the case of a 42 years old male, with a bipolar disorder and receiving lithium therapy, valproic acid and clonazepam. Due to an exacerbation of his underlying disease, he was admitted to a psychiatric clinic and received 50 mg of intramuscular chlorpromazine in 2 ocasions. Afterwards, the patient had an alteration of conciousness, fever reaching 39ºC and generalized muscular rigidity. Laboratory work-up showed a normal brain CT scan, a diffuse slowness in the EEG and a creatinphosphokinase that reached values of 3.040 U/l. He was transferred to an intensive care unit and treated with sodium dantrolene and bromocriptine, obtaining a good clinical response

Neuroleptic malignant syndrome.

Neuroleptic malignant syndrome is a relatively uncommon life-threatening disorder. The widespread use of the neuroleptic and psychotropic medications, however, makes it important for the primary care physician to understand the clinical presentation, differential diagnosis, and management of neuroleptic malignant syndrome. Early recognition should be possible. Rapid diagnosis followed by aggressive supportive care and specific pharmacologic therapy can be life saving.

Urgências em psiquiatria / Psychiatric urgencies

A propósito das urgências psiquiátricas, tais como sídromes histérica, ansiosa, de abstinência ao alcool, de agitaçäo psicomotora e depressiva, o autor faz comentários genéricos e expöe orientaçöes ao médico plantonista, denominado "médico de dia", no âmbito dos hospitais da Aeronáutica. A forma de abordagem, desde o manejo verbal à contençäo física, é detalhada de modo a consolidar a conduta a ser adotada pelo médico assistente em cada caso. Enfatiza que o médico que presta o atendimento use o bom senso, expresse firmeza, confiança e disponibilidade para o atendimento

Síndrome neuroléptica maligna: relato de caso / Neuroleptic malignant syndrome: a case report

A Síndrome Neuroléptica Malígna (SNM) é uma rara, mas provavelmente subdiagnosticada, complicação do tratamento com neurolépticos. Sendo potencialmente fatal, o seu diagnóstico precoce é de fundamental importância. Um caso característico de SNM é apresentado, sendo discutido aspectos diagnósticos e terapêuticos