Neuroleptic Malignant Syndrome Research Articles

Neuroleptic malignant syndrome secondary to olanzapine, a presentation with severe acute kidney injury requiring hemodialysis: a case report

BackgroundWe present this case to draw attention to the importance of early diagnosis in terms of life-saving, noting that greater awareness is important among healthcare professionals. Our patient developed neuroleptic malignant syndrome (NMS) after his neuroleptic drug dosage was increased. His condition was complicated by acute kidney injury (AKI) which required hemodialysis. The uniqueness of this case is that the causative agent of NMS is an atypical antipsychotic, and atypical antipsychotics are generally considered to be safer than typical antipsychotics.Case presentationA 31-year-old Chinese man with underlying schizophrenia presented to our hospital with aggressive behavior. He was admitted to the psychiatric hospital and started on his regular medications, with an increase in the dose of olanzapine tablet from 5 to 10 mg daily. After 5 days in the ward, the patient was noted to have high fever, restlessness, confusion, increased muscle rigidity, tachycardia and tachypnoea. Antipsychotic therapy was stopped in view of suspected NMS. The first laboratory test for serum creatine kinase (CK) showed a markedly high level of this molecule. His renal profile showed raised serum creatinine in comparison to 2 months prior when the baseline serum creatinine was within the normal range. A diagnosis of NMS with AKI was made. Although the patient was given adequate intravenous fluid hydration with close monitoring of urine output, his renal function did not show improvement but continued to show a worsening trend. In view of this, he was started on urgent hemodialysis. The patient was dependent on intermittent hemodialysis before his AKI showed complete recovery. After 2 weeks, his blood test results returned to normal. He was discharged well.ConclusionNeuroleptic malignant syndrome is a life-threatening iatrogenic medical emergency in which high index of clinical suspicion is required for diagnosis and prompt treatment.

NEUROLEPTIC MALIGNANT SYNDROME: AN UNUSUAL CASE TO INCREASE CLINICAL ATTENTION

A 26-year-young man was taken to the hospital with symptoms of schizophrenia, and treatment began with a high dose of antipsychotic medication. After receiving medication for 3–4 days, the patient experienced persistently high body temperatures, tight muscles, and raised blood levels of CK-MB and CK-NAC. The results of all other investigations were normal. A rare Neuroleptic Malignant Syndrome (NMS) was made and treatment started with immediate withdrawal of the causative drug, and timely supportive therapy led to a successful recovery. This case illustrates the importance of adopting a broad differential diagnosis for fever, carefully reviewing the prescription lists of all patients, and taking NMS into account in patients who have both fever and stiffness.

TOO HOT TO GET DRESSED?

TOO HOT TO GET DRESSED?

An atypical presentation of scrub typhus

Scrub typhus is caused by Orientia tsutsugamushi, characterised by focal or disseminated vasculitis and perivasculitis which may involve the lungs, heart, liver, spleen and central nervous system. The clinical picture and severity of the symptoms varies widely. The neurological manifestations of scrub typhus are diverse. Meningoencephalitis is classical manifestation of scrub typhus but cerebellitis, cranial nerve palsies, plexopathy, transverse myelitis, neuroleptic malignant syndrome and Guillain-Barre syndrome are other manifestations reported in literature. The availability of literature on the neurological manifestations of scrub typhus is limited to case reports mainly. This article shows a case report of neurological manifestations of scrub typhus.

Intravenous dantrolene in hypermetabolic syndromes: a survey of the U.S. Veterans Health Administration database

BackgroundIntravenous dantrolene is often prescribed for hypermetabolic syndromes other than the approved indication of malignant hyperthermia (MH). To clarify the extent of and indications for dantrolene use in conditions other than MH, we sought to document current practices in the frequency, diagnoses, clinical characteristics and outcomes associated with dantrolene treatment in critical care settings.MethodsInpatients receiving intravenous dantrolene from October 1, 2004 to September 30, 2014 were identified retrospectively in the U.S. Veterans Health Administration national database. Extracted data included; diagnoses of hypermetabolic syndromes; triggering drugs; dantrolene dosages; demographics; vital signs; laboratory values; in-hospital mortality; complications; and lengths of stay. Frequency and mortality of patients who did not receive dantrolene were obtained in selected diagnoses for exploratory comparisons.ResultsDantrolene was administered to 304 inpatients. The most frequent diagnoses associated with dantrolene treatment were neuroleptic malignant syndrome (NMS; N = 108, 35.53%) and sepsis (N = 47, 15.46%), with MH accounting for only 13 (4.28%) cases. Over half the patients had psychiatric comorbidities and received psychotropic drugs before dantrolene treatment. Common clinical findings in patients receiving dantrolene included elevated temperature (mean ± SD; 38.7 ± 1.3 °C), pulse (116.33 ± 22.80/bpm), respirations (27.75 ± 9.58/min), creatine kinase levels (2,859.37 ± 6,646.88 IU/L) and low pO2 (74.93 ± 40.16 mmHg). Respiratory, renal or cardiac failure were common complications. Mortality rates in-hospital were 24.01% overall, 7.69% in MH, 20.37% in NMS and 42.55% in sepsis, compared with mortality rates in larger and possibly less severe groups of unmatched patients with MH (5.26%), NMS (6.66%), or sepsis (41.91%) who did not receive dantrolene.ConclusionsIn over 95% of cases, dantrolene administration was associated with diagnoses other than MH in critically-ill patients with hypermetabolic symptoms and medical and psychiatric comorbidities. Exploratory survey data suggested that the efficacy and safety of dantrolene in preventing mortality in hypermetabolic syndromes other than MH remain uncertain. However, randomized and controlled studies using standardized criteria between groups matched for severity are essential to guide practice in using dantrolene.

Clozapine as a treatment for catatonia: A systematic review

Catatonia is a neuropsychiatric disorder characterised by altered movement, speech, and behaviour. Clozapine is an established therapy for treatment-resistant schizophrenia, but its role in catatonia has not been systematically examined. In this systematic review, we aimed to assess the evidence for clozapine as a treatment for catatonia.Full text original research articles in English where at least one patient with catatonia was treated with clozapine were included, provided catatonia did not occur solely in the context of neuroleptic malignant syndrome. Results were tabulated with calculations of summary statistics presented. Risk of bias was assessed with the Tool for Evaluating the Methodological Quality of Case Reports and Case Series.182 patients were included, 81 from cohort studies and 101 from case reports or case series. 119/182 patients (65 %) had a specified underlying diagnosis of schizophrenia. Over 80 % of reported patients with catatonia had at least partial remission following treatment with clozapine across both cohort studies and case reports and case series. Among the case reports and series, 24/101 patients (23.8 %) followed clozapine withdrawal. Overall, 25 studies were of low quality, 60 of moderate quality and 8 of high quality.Our findings should be interpreted with caution, as the reliance on case reports, case series and small cohort studies is susceptible to reporting biases, regression to the mean and confounding by other treatments. Future research could use large healthcare databases to ascertain outcomes in those on clozapine with a history of catatonia given the difficulty and expense of conducting randomised controlled trials.

A case of fulminant neuroleptic malignant syndrome with COVID-19

A case of fulminant neuroleptic malignant syndrome with COVID-19

Analysis of adverse drug events in patients with bipolar disorders using the Japanese Adverse Drug Event Report database.

The aim of the present study was to survey adverse drug events (ADEs) in patients with bipolar disorders and identify risk factors using the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system. Data on patients with bipolar disorders were extracted from the JADER database. The Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PT) and standardized MedDRA queries (SMQ) were used to define ADEs. A multiple logistic regression analysis was performed to identify risk factors for ADEs. A total of 8653 reports of 1108 types of ADEs (PT) were registered in data collected on 3521 patients with bipolar disorders. Rash (PT) was the most frequently reported in 549 patients, followed by drug eruption (PT) in 387, fever (PT) in 364, toxicity to various agents (PT) in 291, and Stevens-Johnson syndrome (PT) in 261. Among 24 ADEs (PT) that were reported in more than 50 patients, lamotrigine was associated with increased risks of 13 ADEs (PT), followed by carbamazepine with increased risks of 8 ADEs (PT). The majority of these ADEs belonged to hypersensitivity (SMQ) or hepatic disorder (SMQ). Lithium carbonate was associated with increased risks of rash (PT), drug interaction (PT), and tubulointerstitial diseases (SMQ). All antipsychotics increased the adjusted odds ratio for neuroleptic malignant syndrome (PT). The risk of hyperglycemia/new onset diabetes mellitus (SMQ) was increased by olanzapine, quetiapine fumarate, and risperidone. We are presenting the profiles of ADEs in patients with bipolar disorders using the JADER database, and propose risk factors for 19 ADEs (PT) and 4 ADEs (SMQ).

Anaesthesia and Perioperative Management for Patients with Parkinson's Disease

Idiopathic Parkinson's syndrome is associated with the loss of dopaminergic cells. It is defined by the presence of akinesia together with one of the cardinal symptoms: rigor, tremor, or postural instability. As the perioperative management of these patients can be challenging and they have an increased perioperative risk, every anaesthesiologist should know some special features. If a patient with Parkinson's disease does not receive the required amount of dopa, akinetic crisis may occur. Moreover, the administration of dopamine-antagonistic drugs can trigger a malignant neuroleptic syndrome. These are life-threatening clinical pictures that require intensive medical treatment. Therefore, patients with Parkinson's disease should be enabled to keep the period without the intake of the specific medication as short as possible. General anaesthesia should be performed with short acting anaesthetics and a regional anaesthesia might be beneficial. Besides, all dopamine antagonists sometimes used for prophylaxis or therapy of delirium or PONV (haloperidol, metoclopramide) are contraindicated. Alternatives are short-acting benzodiazepines, atypical neuroleptics and domperidone.

Silent Neuroleptic Malignant Syndrome: A Case Report of Atypical Antipsychotic Induced Elevation of Creatinine Kinase and Altered Mental Status.

34-year-old African American male with a diagnosis of schizophrenia was placed on aripiprazole and risperidone for psychosis and mood stabilization. Two days after medication initiation, the patient's mentation was altered and he appeared confused with an elevated creatine kinase (CK) at 7101. Medications were held and CK normalized with IV fluids. Quetiapine was initiated after medical stabilization along with lithium and paliperidone palmitate injections. After the second dose of paliperidone palmitate, the patient's mentation was altered, and repeat CK was 4272. The patient received 4 liters of IV fluid and his mental status returned to baseline. There were two case studies noted that had marked increases in serum CK with risperidone use. The first was in an adolescent who was titrated to a dose of risperidone 3mg/ day but the only abnormality was an increase in his CK levels. The next case report was in a 40-year-old female who was on risperidone 2.5mg /day for one year. She had an intention tremor, minor muscle weakness of the lower extremities with a blood pressure of 140/100 and a pulse of 100. She manifested more clinical signs of possible Neuroleptic Malignant Syndrome (NMS). This case highlights the importance of laboratory investigations when there is a high suspicion of possible NMS. It also highlights that some cases of NMS may only present as altered mental status and increased CK in which quick treatment may lead to the prevention of full-blown clinical manifestations of NMS which could be life-threatening.

Serotonin Syndrome after PACU Administration of Tramadol and Meperidine.

Serotonin syndrome, malignant hyperthermia, and neuroleptic malignant syndrome are life-threatening conditions with similar clinical presentations, all of which may occur in post-operative patients. The rarity of these conditions has limited their research as well as the ability to recognise and treat them effectively. We present the case of a 61-year-old male who developed altered mental status, respiratory distress, fever, and haemodynamic instability following post-operative administration of tramadol and meperidine. The differential diagnosis process and process of elimination were used to diagnose this patient with serotonin syndrome. Chart review was used to review the details of the case to write this report. Serotonin syndrome was eventually diagnosed in the context of the symptoms following the administration of 2 serotonergic agents. The patient’s symptoms improved with supportive care and did not recur. This case is one of the first published reports of serotonin syndrome resulting from an interaction between tramadol and meperidine, highlighting the importance of constant vigilance in the perioperative period when serotonergic agents are involved. The increased usage of serotonergic antidepressants and Enhanced Recovery After Surgery protocols calling for serotonergic analgesics represent a significant and underrecognised potential for serotonergic multidrug interactions to occur.

Concomitant neuroleptic malignant syndrome and diabetes insipidus.

Each year, nearly one-fifth of adults in the United States are prescribed at least one psychotropic medication. An increased trend in psychiatric polypharmacy has heightened awareness of drug-drug interactions and the tracking of adverse drug reactions. This article describes a patient who developed concomitant neuroleptic malignant syndrome (NMS) and nephrogenic diabetes insipidus during cross-titration of his antipsychotics while on lithium. The patient's mild form of NMS in turn caused hypovolemia and acute kidney injury. This case study highlights the dangers of polypharmacy and how it can obscure the presentation of even classic adverse reactions.

Drug-Induced Hyperthermia Review.

Humans maintain core body temperature via a complicated system of physiologic mechanisms that counteract heat/cold fluctuations from metabolism, exertion, and the environment. Overextension of these mechanisms or disruption of body temperature homeostasis leads to bodily dysfunction, culminating in a syndrome analogous to exertional heat stroke (EHS). The inability of this thermoregulatory process to maintain the body temperature is caused by either thermal stress or certain drugs. EHS is a syndrome characterized by hyperthermia and the activation of systemic inflammation. Several drug-induced hyperthermic syndromes may resemble EHS and share common mechanisms. The purpose of this article is to review the current literature and compare exertional heat stroke (EHS) to three of the most widely studied drug-induced hyperthermic syndromes: malignant hyperthermia (MH), neuroleptic malignant syndrome (NMS), and serotonin syndrome (SS). Drugs and drug classes that have been implicated in these conditions include amphetamines, diuretics, cocaine, antipsychotics, metoclopramide, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and many more. Observations suggest that severe or fulminant cases of drug-induced hyperthermia may evolve into an inflammatory syndrome best described as heat stroke. Their underlying mechanisms, symptoms, and treatment approaches will be reviewed to assist in accurate diagnosis, which will impact the management of potentially life-threatening complications.

Antipsychotics for schizophrenia spectrum disorders with catatonic symptoms.

Antipsychotics for schizophrenia spectrum disorders with catatonic symptoms.

Drug-induced hyperthermia with rhabdomyolysis in CLN3 disease.

CLN3 disease (MIM# 204200), the most prevalent of the neuronal ceroid lipofuscinoses (NCL), is an autosomal recessive disorder with juvenile onset characterized by blindness, epilepsy, dementia, psychiatric manifestations, and motor deterioration. Problems related to behavior, emotions and thought are among the main features. Antidepressant and antipsychotic drugs have been employed with variable results. Neuroleptic malignant syndrome (NMS) has previously been described in two patients with NCL, one with CLN3 disease and one with adult onset NCL of unclear genetic origin. Our aims were to describe the occurrence of drug-induced hyperthermia in pediatric patients with CLN3 disease from West and South Sweden and to delineate the range of associated clinical features. Our study identified four patients presenting with seven episodes of severe drug-induced hyperthermia and either NMS-like or Serotonin syndrome (SS)-like features. Possibly provoking drugs were risperidone, clozapine, olanzapine, haloperidol, quetiapine, and sertraline. The course was atypical, frequently prolonged, associated with rhabdomyolysis and status dystonicus, and resulted in the death of three of the patients. Our study points to a vulnerability to drug-induced hyperthermia in patients with CLN3 disease which we believe could be underreported. Interestingly the proposed pathophysiological mechanisms behind NMS and SS on one hand and CLN3 on the other hand seem to converge in a common mechanism involving dysregulation of the sympathetic nervous system.

Electroconvulsive Therapy in Psychiatric Disorders: A Narrative Review Exploring Neuroendocrine-Immune Therapeutic Mechanisms and Clinical Implications.

Electroconvulsive therapy (ECT) is based on conducting an electrical current through the brain to stimulate it and trigger generalized convulsion activity with therapeutic ends. Due to the efficient use of ECT during the last years, interest in the molecular bases involved in its mechanism of action has increased. Therefore, different hypotheses have emerged. In this context, the goal of this review is to describe the neurobiological, endocrine, and immune mechanisms involved in ECT and to detail its clinical efficacy in different psychiatric pathologies. This is a narrative review in which an extensive literature search was performed on the Scopus, Embase, PubMed, ISI Web of Science, and Google Scholar databases from inception to February 2022. The terms “electroconvulsive therapy”, “neurobiological effects of electroconvulsive therapy”, “molecular mechanisms in electroconvulsive therapy”, and “psychiatric disorders” were among the keywords used in the search. The mechanisms of action of ECT include neurobiological function modifications and endocrine and immune changes that take place after ECT. Among these, the decrease in neural network hyperconnectivity, neuroinflammation reduction, neurogenesis promotion, modulation of different monoaminergic systems, and hypothalamus–hypophysis–adrenal and hypothalamus–hypophysis–thyroid axes normalization have been described. The majority of these elements are physiopathological components and therapeutic targets in different mental illnesses. Likewise, the use of ECT has recently expanded, with evidence of its use for other pathologies, such as Parkinson’s disease psychosis, malignant neuroleptic syndrome, post-traumatic stress disorder, and obsessive–compulsive disorder. In conclusion, there is sufficient evidence to support the efficacy of ECT in the treatment of different psychiatric disorders, potentially through immune, endocrine, and neurobiological systems.

Neuroleptic Malignant Syndrome: Typical Antipsychotic Drugs Versus Atypical Antipsychotic Medications

Introduction: Neuroleptic malignant syndrome is an idiosyncratic reaction and a severe disorder caused by an adverse reaction to drugs with dopamine receptor- antagonist properties and is characterized by a tetrad of rigidity, fever, altered mental status, and autonomic instability. In the present assessment, typical or conventional antipsychotics have been contrasted with atypical antipsychotics with respect to recorded cases of neuroleptic malignant syndrome among a sample of nonwestern psychiatric inpatients. Methods: For assessment, all the cases with a diagnosis of neuroleptic malignant syndrome during the last sixty-two months, after exclusion of other conceivable differential diagnoses, were incorporated in the current retrospective, record-based evaluation. The clinical diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. The valuation of independent variables was analyzed by ‘Compression of proportions. Statistical significance is defined as p value ≤0.05. Results: Amongst 19814 psychiatric inpatients, in the course of sixty-two months, eighteen cases received the diagnosis of neuroleptic malignant syndrome. As said by the findings, neuroleptic malignant syndrome was meaningfully more frequent among males, in comparison with females, and it was importantly more prevalent among cases suffering from schizophrenia, in comparison with bipolar disorder. Also, the highest risk of neuroleptic malignant syndrome was found in the age group of 30-39. In the current assessment, only one of the patients, who had received haloperidol, died due to aspiration pneumonia and respiratory failure, and the most prevalent symptom was fever, which was observable in one hundred percent of cases. In addition to a similar clinical profile, ‘Compression of proportions’ did not show any significant difference between the conventional (typical) antipsychotics versus the atypical antipsychotic medications with respect to the occurrence of neuroleptic malignant syndrome. Conclusion: As said by the findings, no significant difference was evident between the typical antipsychotic drugs versus the atypical antipsychotic medications, with respect to incidence and clinical profile of neuroleptic malignant syndrome.

Differentiating probable nitrofurantoin-induced drug fever from antipsychotic-induced hyperthermia in a patient receiving clozapine

Nitrofurantoin (NIT) is a commonly utilized antibiotic for the treatment of UTIs. Although well tolerated, NIT is not without potential adverse reactions. This case report details the observation of probable NIT-induced drug fever in a patient receiving clozapine. A 61-year-old female with treatment-refractory schizoaffective disorder was admitted to a psychiatric unit with paranoia and auditory hallucinations, prompting clozapine initiation during day 1 of hospitalization. Due to worsening hallucinations and anxiety, antibiotic therapy with NIT for a presumed UTI was initiated 8 days after admission. Febrile episodes were observed beginning on hospital day (HD) 9, leading to concern for possible neuroleptic malignant syndrome (NMS), which led to clozapine discontinuation. The patient received a total of 3 doses of NIT with continued fever until discontinuation on HD 10. No further complications were encountered, and clozapine was safely resumed on HD 13. Although sparsely described in the medical literature, occurrences of drug fever attributable to NIT are previously reported. A review of the medical literature identified only 5 previously published articles specific to NIT-induced drug fever, none of which specified interruptions of psychotropic therapy for a patient with acute psychiatric decompensation. This case highlights the differential diagnosis of fever related to NIT in a patient receiving clozapine when NMS was initially suspected.

The Evaluation of North Wales SPiCE: Special Preparation in CASC Examination

AimsAs part of the effort to support core psychiatry trainees in North Wales to prepare for their CASC (Clinical Assessment and Skill Competency) exam, the North Wales SPiCE (Special Preparation in CASC Examination) Project has been initiated. This article aims to evaluate the SPiCE based on medical educational principles.MethodsA total of five candidates preparing for the CASC exam expressed interest and an organising committee was set up. Examiners consisted of a consultant and four specialist registrars while role players were recruited from non-exam sitting junior trainees. Five mock CASC stations were written and role-players were calibrated accordingly. The stations included: History taking for a patient with FTD (frontotemporal lobe dementia), MSE (Mental state examination) of a patient with mania and psychosis, explanation of CBT (cognitive-behavioural therapy), breaking bad news of NMS (neuroleptic malignant syndrome), and explanation of ECT (electroconvulsive therapy). The mock exam was conducted virtually using Microsoft TeamsTM. The specialist registrars’ performances in feedback provision were assessed for their teaching using the AOT (Assessment of Teaching) form by the consultants. For core trainees who had played the part of organising committee members and role players, their volunteerism and educational management experience were assessed using the DONCS (Direct Observation of Non-clinical Skill) form by specialist trainees.ResultsAll five candidates passed all the stations (consists of both borderline pass, pass) in the mock exam with 25% improvements in confidence level were seen among candidates in four stations, i.e. ECT explanation, breaking bad news of NMS, CBT explanation, and MSE of a patient with mania and psychosis. All candidates feel the SPiCE programme was useful in helping their final preparation and they would recommend it to other candidates. Four of the candidates sat for the immediate CASC diet after the SPiCE received a pass result. All specialist registrars received positive AOT feedback for their teaching and all non-exam sitting junior trainees received positive DONCS feedback for their spirit of volunteerism and collaborative teamwork.ConclusionThe main strength of the SPiCE project is it utilises existing resources and volunteerism of the organising committee while its main limitation is it has only five stations rather than 16 stations in the real exam. Although the mock exam has improved the confidence of candidates and the majority of candidates pass the exam immediately after that, the causal link between the SPiCE and candidates’ results cannot be conclusively established given all candidates have a good baseline.

Electroconvulsive therapy in children and adolescents

IntroductionDespite its good results and tolerability in adults, electroconvulsive therapy (ECT) is barely administered in children and adolescents, with scarce evidence in these patients.ObjectivesWe aim to summarize the data available to give a clearer view of how children and adolescents might benefit from ECT.MethodsWe’ve done a bibliographic review in PubMed and Cochrane Library searching for articles that include the terms “electroconvulsive therapy” and “adolescents” and/or “children” and their variations.ResultsCurrent evidence supports the use of ECT in various indications as mood disorders, schizophrenia spectrum disorders, catatonia, neuroleptic malignant syndrome and self-injurious behaviours associated with autism, Tourette’s syndrome or intellectual disability. The efficacy and safety it’s comparable to adults and there are no absolute contraindications. Side-effect profile it’s also similar to the general population, reporting as the most frequent adverse effects headache, generalized body aching, and nausea or vomiting.ConclusionsECT is an effective and safe treatment for severe mental disorders in children and adolescents.DisclosureNo significant relationships.