Neuroleptic Malignant Syndrome Research Articles

Dual Toxidrome of Anti-cholinergic Storm and Neuroleptic Malignant Syndrome: A Therapeutic Challenge Overcome by Intrathecal Neostigmine

Anticholinergic toxicity and neuroleptic malignant syndrome (NMS) are common toxidromes in medical emergencies. However, their co-occurrence, resulting in a dual toxidrome, is rare and presents significant diagnostic and therapeutic challenges. We present the case of a 23-year-old young male with polysubstance dependence, admitted following combined trihexyphenidyl and risperidone toxicity. He was diagnosed with a dual toxidrome of anticholinergic storm and NMS. Treatment of NMS included lorazepam and bromocriptine. Due to the unavailability of physostigmine, the preferred antidote for anticholinergic syndrome, intrathecal neostigmine was administered. The patient subsequently recovered and was discharged. This case highlights the complexity of managing dual toxidromes and the need for alternative therapeutic strategies in resource-limited settings.

Neuroleptic Malignant Syndrome - review of pathophysiology, clinical presentation, differentiation and management

Introduction and purpose: The number of invented and produced medications has increased over recent years. Besides their positive impact on health, they invariably provide various kinds of side effects. This review is focused on malignant neuroleptic syndrome, a rare condition with no fully confirmed pathogenesis, which at least partially can be explained as an adverse effect of blocking dopamine receptors. Even though it usually affects psychiatric or neurological patients, doctors of all medical specializations should stay alert, as the condition can often lead to premature death. Brief description of knowledge: The main symptoms associated with NMS are hypertonia, hyperpyrexia, autonomic instability and altered consciousness. They can appear in any configuration, sometimes followed by less characteristic manifestations. It should be primarily differentiated from serotonin syndrome, malignant hyperpyrexia and catatonia, mostly through the interview of those who have taken medications and undergone surgeries, as there are not any specific lab tests available. Fundamental treatment methods consist of neuroleptic withdrawal, intensive supportive care, drug administration and eventually ECT. Summary: NMS is an uncommon, severe disease that should be carefully considered in patients treated with neuroleptics. Due to its rarity and sudden onset, it appears to be problematic to conduct widespread research and studies, so there are still no concrete, consistent and unquestioned guidelines on recognizing and treating the condition.

Clozapine abrupt cessation fueling overlap Neuroleptic Malignant Syndrome and Serotonin Syndrome with oculomotor dysfunction, A Case report.

Neuroleptic Malignant Syndrome (NMS) and Serotonin Syndrome (SS) are life-threatening conditions caused by adverse reactions to neuroleptics and antidepressant medications. The overlap of both syndromes is rare but has been described previously. Differentiating between both entities based on the clinical presentation can be difficult. We present a case of a young male patient with history of schizophrenia, admitted to the Medical Intensive Care Unit (MICU) for septic shock, who developed NMS and SS with oculomotor dysfunction following the abrupt cessation of clozapine while still being on an antidepressant.

Aripiprazole-induced quasi-neuroleptic malignant syndrome: two case reports

BackgroundSignificant elevation of creatine kinase levels (above three digits) and leucocytosis in the absence of muscle rigidity, tremors, or autonomic dysfunction can pose a real challenge in the context of antipsychotic treatment as an early herald of neuroleptic malignant syndrome.Case presentationWe present here two cases of adult male patients of Black British heritage, ages 51 years and 28 years, respectively. Both received a diagnosis of schizoaffective disorder and presented with massive increase of creatine kinase blood level after aripiprazole depot administration, one with pernicious increase associated with silent neuroleptic malignant syndrome, and the second with asymptomatic benign enzyme elevation.ConclusionThough aripiprazole use is less likely to cause neuroleptic malignant syndrome, on rare occasions it can produce massive symptomatic or asymptomatic increase in serum creatine kinase enzyme levels, raising the need for close monitoring, especially at the initial doses of the drug.

Acute Disseminated Encephalomyelitis (ADEM) Presenting as Neuroleptic Malignant Syndrome (NMS) (P7-14.017)

Acute Disseminated Encephalomyelitis (ADEM) Presenting as Neuroleptic Malignant Syndrome (NMS) (P7-14.017)

Disentangling the Diagnoses of Psychotic Depression, Catatonia, Neurocognitive Disorders, and Delirium: A Multidisciplinary Approach

An ambiguous clinical presentation can create diagnostic uncertainty, leading to delays in effective interventions and increasing the likelihood of adverse clinical outcomes. Unfortunately, many psychiatric conditions share overlapping clinical symptoms. Psychotic depression, catatonia, neurocognitive disorders, and delirium are all examples of distinct clinical conditions with overlapping symptomatology, and all require decidedly different therapeutic interventions. While much literature is devoted to the diagnostic criteria and management of these clinical conditions, little is dedicated to the challenge of disentangling these diagnoses when faced with a complex clinical presentation.We present here a complicated psychiatric inpatient hospitalization of a 77-year-old male who exemplified this diagnostic challenge. He primarily presented with severely depressed mood and decreased functionality, remaining in bed for much of the day with little attention to basic hygiene and oral intake. While records from a recent outside hospitalization carried a historical diagnosis of catatonia, his moderate level of engagement with providers and somatic delusion of disseminated prostate cancer suggested an alternate diagnosis of psychotic depression. However, before a diagnostic conclusion could be reached, other clinical characteristics surfaced. Following a singular administration of olanzapine shortly after his initial assessment, he developed Lilliputian hallucinations, prominent parkinsonism, and significantly altered mentation.Neuroleptic sensitivity raised clinical suspicion for an underlying neurocognitive disorder such as dementia with Lewy bodies, and a consult was placed to the neuropsychology service. While dementia could not be fully ruled out, they did recommend additional workup to rule out herpes simplex encephalitis, autoimmune limbic encephalitis, and paraneoplastic syndromes. After his MRI imaging revealed moderate microvascular ischemic changes, a true multidisciplinary approach to care was taken, as neurology was consulted to also help narrow the differential. An EEG was unremarkable and a serum encephalitis panel was also unremarkable. Olanzapine was discontinued with significant improvement in parkinsonism and cognition; however, severe neurovegetative symptoms and somatic and nihilistic delusions persisted. While antipsychotics remained clinically indicated for a suspected depression with psychotic features, caution was taken due to established neuroleptic sensitivity, subtle catatonic features, and the related risks of neuroleptic malignant syndrome. Ultimately, low-dose quetiapine was initiated with some benefit; however, he continued to remain acutely depressed and withdrawn with prominent negativism. Trials with benzodiazepines for these catatonic features were also approached with caution to avoid potential risks of delirium.Over time, a multidisciplinary approach to psychopharmacologic interventions and medication trials led the team to a principal diagnosis of major depressive disorder with psychotic features and subtle catatonia. The abrupt changes observed early in the hospital course were determined to be related to olanzapine-induced anticholinergic delirium. With greater diagnostic certainty, the team was able to counsel the patient and family about the importance of pursuing electroconvulsive therapy (ECT). The patient's cardiovascular risk factors and known microvascular changes were considered in the determination of the appropriateness for ECT. After starting ECT, he was immediately noted to have objective improvement, and following his fifth treatment, he was deemed appropriate for discharge after exhibiting significant improvement in depression and functionality and reporting near-resolution of somatic delusions. He was able to complete ECT on an outpatient basis and follow-up visits note durable improvements in mood, functionality, and quality of life, continuing to enjoy an active lifestyle of socializing with family and playing tennis. We use this case to further explore the clinical challenges that stem from the symptomatic similarity between psychotic depression, catatonia, neurocognitive disorders, and delirium and discuss optimal therapeutic approaches when the presentation appears complex and equivocal.

Macroglossia Revealing a Neuroleptic Malignant Syndrome: a Clinical Images

Neuroleptic malignant syndrome is a rare and potentially fatal side effect that can occur in response to treatment with antipsychotic drugs. It is characterized by four main symptoms: Impaired mental function, fever, muscle rigidity and autonomic dysfunction. We report the case of a 20-year-old patient, followed for psychosis, in whom a new therapeutic line was adapted 3 days ago: Largactil (chlorpromazine) and Haldol (Haloperidol), who presented to the maxillofacial emergency department with tongue laceration. Clinical examination revealed in an agitated, uncooperative tachycardic and apyretic patient, revealed a generalized muscular spasm associated with trismus attacks, causing tongue injuries due to the installed macroglossia.

Antipsychotic-associated neuroleptic malignant syndrome (NMS) in schizophrenia patients: a narrative review

Neuroleptic malignant syndrome (NMS) is a neurological disorder with an high mortality rate among schizophrenia patients who receive antipsychotics as the primary long-term therapy. Appropriate selection of antipsychotics in NMS should be carefully considered to obtain maximal effectiveness with minimal side effects. An evaluation of the safety profile of the antipsychotics is important due to their different treatment patterns and rapid onset of symptoms. This review article aimed to compare the safety profile of antipsychotics in relation to NMS in schizophrenia patients. It was a narrative review using multiple search engines included PubMed, Google Scholar, and Springer to collect publications from 2007 to 2023. Of the total 14 articles reviewed, 7 articles explained the role of antipsychotics in NMS, 5 articles about the onset of NMS, and 7 articles about mortality rate. The incidence of NMS was less then 0.11%, typical antipsychotics were the most common cause of NMS, especially high-potency antipsychotics compared with atypical antipsychotics. Meanwhile, the onset of NMS consistently occured within 30 d of antipsychotic initiation with a symptom duration of 1 to 30 d, and the mortality rate was also higher for typical antipsychotics. In conclusion, the choice of antipsychotics must be carefully considered and its use must be monitored due to the rapid onset and high mortality. The use of antipsychotics is not free from the risk of NMS. The heterogeneous symptoms of NMS require earlier detection to reduce disease progression.

Neuroleptic malignant syndrome: a neuro-psychiatric emergency

Characterised by fever, altered mental status, muscle rigidity and autonomic dysfunction, neuroleptic malignant syndrome is a life-threatening idiosyncratic reaction to antipsychotic medication; around one in 10 cases end in cardiac arrest. The primary cause of neuroleptic malignant syndrome is dopamine receptor blockade, and the standard causative agent is an antipsychotic drug. While first-generation (typical) neuroleptics such as haloperidol, fluphenazine, trifluoperazine and prochlorperazine pose the greatest risk, neuroleptic malignant syndrome has been reported with second-generation (atypical) neuroleptics such as risperidone, clozapine, olanzapine and ziprasidone. Paramedic awareness of neuroleptic malignant syndrome as a neuropsychiatric emergency is paramount to reducing serious morbidity and even death in patients presenting with symptoms and a history of antipsychotic use. Treatment is individualised and based on clinical presentation, with supportive medical therapy being a key intervention.

First generation antipsychotic-associated serious adverse events in women: a retrospective analysis of a pharmacovigilance database.

Women have been under-represented in trials of antipsychotic medications. Our primary objective was toevaluate five adverse events (AE) associated with first-generation antipsychotics (FGAs) among women relative to menthrough an analysis of the FDA Adverse Event Reporting System (FAERS). We queried 24.6 million AE reports from 2000 to 2023 involving FGAs. The study cohort consisted of chlorpromazine (n = 3317), fluphenazine (n = 1124), haloperidol (n = 16,709), loxapine (n = 3151), perphenazine (n = 816), thioridazine (n = 665), thiothixene (n = 244), and trifluoperazine (n = 360). Cases of neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), Torsades de Pointes (TdP), agranulocytosis (AG), and cerebrovascular adverse events (CVAE) were identified. Reporting odds ratios (ROR) and associated 95% confidence intervals (CI) were calculated with logistic regression for each AE among women relative to men. A total of 2,857 serious AEs were evaluated in the study cohort (NMS = 1810, TD = 434, TdP = 260, AG = 149, CVAE = 204). The ROR for women compared to men was 0.79 (95% CI, 0.71-0.87) for NMS, 0.83 (0.68-1.01) for TD, 1.21 (0.94-1.53) for TdP, 0.71 (0.51-0.98) for AG, and 0.91 (0.68-1.19) for CVAE. A secondary analysis revealed a higher odds in women compared to men of hospitalization associated with reports of TD (ROR = 1.95, 1.29-2.94) and death associated with reports of AG (ROR = 2.46, 1.15-5.24). A subgroup analysis of haloperidol revealed an ROR = 1.67 (1.26-2.21) for women relative to men for TdP. The subgroup analysis of haloperidol AEs revealed a significantly higher reporting odds ratio for TdP. Additionally, the secondary study findings suggest that women were more vulnerable to worse outcomes associated with certain AEs of FGAs.

An afebrile neuroleptic malignant syndrome with hyponatremia: A case report.

Neuroleptic malignant syndrome (NMS) is a rare, life-threatening situation in response to the adverse reaction of antipsychotic medications characterized by high-grade fever, altered Glasgow coma scale, autonomic dysfunction, and stiffness. We herein present a case with a typical presentation of stiffness and autonomic dysregulations along with the atypical symptoms of urinary incontinence and a history of falls. The patient was afebrile with hyponatremia, showing a similar presentation diagnosed as NMS and treated successfully according to the hospital protocol.

Atypical antipsychotic-induced neuroleptic malignant syndrome

The rare neuroleptic malignant syndrome (NMS) is associated with early mortality of >30%. Better supportive care has reduced mortality to <10%. Atypical antipsychotics such as clozapine and risperidone are associated with an atypical but potentially lethal, NMS. A 22-year-old male developed NMS after being treated with clozapine and risperidone for aggression associated with mental retardation for about 8 years. For the past 1 year, the dose of clozapine was 200 mg/day and the dose of risperidone was 8 mg/day. The patient presented with symptoms of hyperthermia, perspiration, neck rigidity, and tonic posturing of all four limbs with tongue bite and frothing from the mouth. On examination, the patient’s Glasgow coma Scale was E3V1M4. He was intubated and given antibiotics, antiepileptic, tablet bromocriptine 2.5 mg (1-1-1-1), and other supportive treatment. The patient showed improvement in 10 days. Knowledge of diagnostic features, risk factors, treatment modalities, and differential diagnosis of NMS is essential. Early diagnosis and prompt treatment can reduce mortality and morbidity significantly.

Neuroleptic Malignant Syndrome with haloperidol in a patient with alcohol withdrawal delirium

Neuroleptic Malignant Syndrome with haloperidol in a patient with alcohol withdrawal delirium

Neuroleptic malignant syndrome following clozapine withdrawal

Neuroleptic malignant syndrome following clozapine withdrawal

Persistent High Fever After Metchloropramide Treatment; Neuroleptic Malignant Syndrome

Introduction: Neuroleptic Malignant Syndrome(NMS) is a state neurotransmitter levels fluctuate subsequent to administration of neuroleptic agents. Etiology of NMS is unclear. It’s a neurological emergency includes symptoms like altered mental status, rigidity, fever and dysautonomy. Our aim in here is to mention the side effects of metochlopramide, which is commonly used in Emergency Departments(ED). In our case, subsequent to intravenous admission of metochlopramide, patients clinic worsened with NMS symptoms and this was quite unexpected and unwanted for ED doctors. By this case report it is wanted to raise awareness against, side effects of metoclopramide and NMS.
 Case Report: Subsequent to intravenous administration of single dose metoclopramide to relieve abdominal pain into 21 years old male with no history of chronical diseases, symptoms of fever, muscle rigidity, confusion and fluctuating blood pressure levels quickly emerged along with leukocytosis and high levels of Creatine Kinase. ED Doctors suspected NMS. Futher laboratory and imaging stuides has excluded other central nervous system pathologies and infections. Eventually, patients clinic got better with symptomatic theraphy and he was discharged fully recovered.
 Conclusion: NMS due to metoclopramide is quite rare, but usage of therapies includes Metoclopramid at ED’s are quite often. Subsequent to administration of this drug, if patients clinical state worsens with fever, confusion and muscle rigidity, phycisians should keep NMS in mind.

Asymptomatic CK Increase in Patient with Neuroleptic Sensitivity after the Development of Neuroleptic Malignant Syndrome

Asymptomatic CK Increase in Patient with Neuroleptic Sensitivity after the Development of Neuroleptic Malignant Syndrome

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

Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with antipsychotics is common in early stages when psychiatric symptoms predominate, and their use has been associated with serious side effects including neuroleptic malignant syndrome (NMS). The observation of adverse response to antipsychotics, raising the suspicion of NMS, has been included as a criterion for possible autoimmune psychosis. 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. A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before referral to our Institution. In this group, thirty-six patients (72%) of the patients 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. Our study supports previous observations about the high frequency of autonomic dysfunction, hyperthermia, tachycardia, rigidity, and elevated CPK 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.

Evaluation of neuroleptic malignant syndrome induced by antipsychotic drugs using spontaneous reporting system

Adverse events (AEs) of antipsychotic drugs include neuroleptic malignant syndrome (NMS), which presents complex clinical symptoms, resulting in a fatal outcome. In this study, the association between antipsychotic drugs and NMS was comprehensively evaluated by cluster and association analyses using the Japanese Adverse Drug Event Report (JADER) database.The analyses were performed using 20 typical antipsychotics (TAPs) alongside 9 atypical antipsychotics (AAPs). The Standardised MedDRA Queries (SMQ) database was used to analyze NMS (SMQ code: 20000044). Reporting odds ratios (RORs) were used for AE signal detection. The relationship between antipsychotic drugs and AEs for NMS was investigated by performing hierarchical cluster analysis using Ward's method.Between April 2004 and September 2021, the total number of JADER reports was 705,294. RORs (95 % confidence interval) of NMS for haloperidol, chlorpromazine, risperidone, and aripiprazole were 12.1 (11.1–13.3), 6.3 (5.7–7.0), 6.2 (5.8–6.6), and 4.7 (4.4–5.1), respectively. Three clusters were formed, with characteristics as follows: Cluster 1 consisted of only TAPs, such as bromperidol and fluphenazine, whilst having a high reporting rate of hypotension, tachycardia, dyskinesia, and dystonia. Cluster 2 consisted of all AAPs alongside several TAPs, such as haloperidol and chlorpromazine, with higher reporting rates of disturbance of consciousness, extrapyramidal disorders (excluding dyskinesia and dystonia), and serotonin syndrome. Cluster 3 consisted of only perphenazine, whilst having a higher reporting rate of coma, leukocytosis, and Parkinsonism.The results of this study may therefore aid in the management of NMS using antipsychotic drugs.

Neuroleptic malignant syndrome after abrupt discontinuation of neuroleptic and anticholinergic drugs

Neuroleptic malignant syndrome after abrupt discontinuation of neuroleptic and anticholinergic drugs

Malignant Neuroleptic Syndrome: From Diagnosis to Management. Experience at Ar-Razi Hospital

Malignant Neuroleptic Syndrome (MNS) is a diagnostic and therapeutic emergency that poses a threat to a patient's life. It represents a rare but severe complication of neuroleptic treatment. It can occur with any antipsychotic, regardless of dosage or administration route. Its exact cause remains unknown. We present a series of 20 cases of MNS in patients hospitalized at Ar-Razi Hospital over a 3-year period, spanning from January 2018 to October 2021. We describe the clinical characteristics of MNS in these patients, the treatments received, the management, and the outcome of this syndrome. The clinical presentation of MNS is heterogeneous, with some patients not meeting all the criteria for MNS. 85% of the patients experienced a favorable outcome without complications. Early recognition of MNS can save lives. In the presence of fever, altered consciousness, generalized rigidity, tachycardia, and labile blood pressure in a patient taking antipsychotics, consider malignant neuroleptic syndrome and discontinue any suspect medication.