Neuroleptic Malignant Syndrome: A Potential Etiology of Multisystem Organ Failure in a Burn Patient.

Neuroleptic malignant syndrome (NMS) is described in the medical literature but rarely seen among acutely ill trauma patients. A 44-year-old man with burns to the hands and back after a chemical explosion was transported to an outside facility where he received treatment for presumed acute coronary syndrome after developing ventricular tachycardia and elevated serum troponins after the exposure. His cardiac catheterization was unremarkable, but an echocardiogram revealed severe cardiomyopathy, and he was also in multisystem organ failure. He was transferred to our facility after hospital day 2 for treatment of his multisystem organ failure and 2% total body surface area burns. His laboratory results were remarkable for a creatine kinase of >100 000 units/L, and he required 14 g of intravenous calcium. Upon further investigation, the patient reported taking ziprasidone for his bipolar disorder, and he had a core temperature of 103.5 °F on his initial presentation to the outside facility. As he convalesced, the unifying diagnosis was NMS. NMS is a side effect of antipsychotic therapy and is manifested by hyperpyrexia, rigidity, autonomic instability, and altered consciousness. An elevated creatine kinase >100 000 units/L is almost pathognomonic for NMS. Patients can also present with leukocytosis, organ failure, and electrolyte disturbances including hypocalcemia. We hypothesized that dehydration, the warm environmental conditions at our patient's job, and immense stress resulting in a catecholamine surge following his trauma were inciting triggers to this event. This case highlights the importance of considering alternate diagnoses in patients whose clinical presentation does not fit the most "obvious cause."

Coexistence of guanidinoacetate methyltransferase (GAMT) deficiency and neuroleptic malignant syndrome without creatine kinase elevation.

We describe the first child with guanidinoacetate methyltransferase (GAMT) deficiency who developed neuroleptic malignant syndrome (NMS) after the treatment of risperidone without elevated creatine kinase (CK) levels. The patient presented with lethargy, hyperthermia, generalized tremor and rigidity with normal serum CK levels. After cessation of risperidone and adding clonezepam to the supportive treatment, symptoms of NMS were ameliorated. We conclude that although serum CK elevation is a useful indicator for the early detection of NMS, normal serum CK levels may be seen during the NMS course in the presence of GAMT deficiency.

Clinical utility of neutrophil-lymphocyte ratio in the diagnosis of neuroleptic malignant syndrome.

Background: Neuroleptic malignant syndrome (NMS) is a life-threatening side effect of antipsychotic medication. In this study, we aimed to investigate the hypothesis of inflammation via neutrophil-lymphocyte ratio (NLR) in the etiology of NMS. Methods: In this retrospective case-control study, data were collected using digital database of Bakirköy Mental Health Research and Training State Hospital by screening NMS diagnosis according to 'International Classification of Diseases (ICD-10) code: G21.0' between the years of 2007 and 2017. We included 32 hospitalizations with the diagnosis of NMS and 31 other acute psychiatric hospitalizations without NMS of same patients. NLR was calculated as proportion of absolute neutrophil count to absolute lymphocyte count. Significance level was accepted as p < .05. Results: The mean NLR value of NMS group was 9.55 ± 5.13 and control group was 2.06 ± 0.71 (p < .001). According to ROC analysis in our study group, we found a mean NLR cutoff value ≥4 and lymphocyte percent cutoff of ≤18.4% have the probability of correctly identifying patients with NMS with the 100% sensitivity and 100% specificity. Conclusions: In this retrospective study, we considered that higher NLR value in NMS episode might be a resemblance of systemic inflammatory state. In addition, our results suggest that both NLR and lymphocyte percentage may be alternative minor criteria which are more sensitive and specific than leukocyte levels and CPK.

Serum osmolarity and blood viscosity as a potential explanation for the pathophysiology of neuroleptic malignant syndrome.

Background: Neuroleptic malignant syndrome (NMS) is a rare but life-threatening side effect. NMS patients usually develop dehydration and fluid-electrolyte imbalance. In this study, we aimed to investigate serum osmolarity and blood viscosity in patients with NMS.Methods: This was a retrospective case-control study including 32 admissions of 27 patients with the diagnosis of NMS. As a control group, 31 non-NMS episodes of hospitalizations of the same patients were included.Results: Serum osmolarity of NMS group was 301.83 ± 20.27 mOsm/L and control group was 294.20 ± 5.92 mOsm/L. Serum osmolarity of NMS group was statistically significantly higher than the controls (p = .018). Whole blood viscosity (WBV) at high shear rate (HSR) value of NMS group was 16.17 ± 1.48 and control group was 16.50 ± 1.38 (p = .331). Regarding WBV at low shear rate (LSR) values, also no statistically significant difference was observed between groups. LSR values of NMS and control group were 39.86 ± 30.11 and 47.41 ± 28.43, respectively (p = .387).Conclusions: Our findings indicate that serum osmolarity of NMS group was statistically significantly higher than the controls. In terms of blood viscosity, there was no statistically significant difference between groups. Higher serum osmolarity in NMS patients than controls may be a reflection of a relative hemoconcentration in NMS.KEY POINTSNMS is usually associated with dehydration resulting in fluid-electrolyte imbalance.We compared the NMS episodes with non-NMS hospitalizations (as control group) of the same patients.Serum osmolarity was statistically significantly higher in NMS group than the controls.There was no statistically significant difference between groups in terms of blood viscosity.

A Pharmacovigilance Approach for Post-Marketing in Japan Using the Japanese Adverse Drug Event Report (JADER) Database and Association Analysis.

BACKGROUND: Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed. METHODS AND FINDINGS: We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA). We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male. CONCLUSIONS: Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions differed by gender. This approach using a large database for examining the associations can improve safety monitoring during the post-marketing phase.

Lethal neuroleptic malignant syndrome due to amisulpride.

A 42-year old-man was found lying in his bed having seizures. Later he became unconscious and hypotonic developing mydriasis as well as rigidity. The body core temperature (rectal temperature) was above 42 °C. Blood pH was decreased during treatment, and his general condition deteriorated. The patient developed gasping respiration, ventricular fibrillation, and died. During autopsy and histological investigation cerebral and pulmonary edema were noted together with general congestion of the internal organs. Further observations included contraction bands of myocytes, a contracted spleen, fibrosis of the liver, and gall stones. Toxicological analyses of peripheral blood revealed the following results: amisulpride 4.65 mg/l, biperiden 0.12 mg/l, imipramine 0.33 mg/l, and desipramine 0.68 mg/l. An amisulpride-induced neuroleptic malignant syndrome was therefore diagnosed as the patho-physiological mechanism leading to death.

Neuroleptic malignant syndrome or a statin drug reaction? A case report.

A 60-year-old woman with a long psychiatric history presented with delirium and mutism. She was febrile, with marked limb rigidity and elevated creatinine kinase (CK) level. Current medications included pericyazine. Current or recent use of dopamine-blocking agents, such as pericyazine, together with a disturbance in conscious state, autonomic dysfunction, and an elevated CK level may be suggestive of neuroleptic malignant syndrome (NMS). The diagnosis was confirmed as NMS, and she was successfully treated with bromocriptine. Eight years later, she represents with symptoms suggesting recurrence of NMS including elevated CK level and myalgia, however, without limb rigidity. Current medications include quetiapine, lithium, simvastatin, and a recent course of clarithromycin. Macrolide antibiotics such as clarithromycin inhibit the metabolic pathway of statins via the cytochrome CYP450 3A4 hepatic enzyme system and may result in elevated CK level, myopathy, or rhabdomyolysis producing symptoms that may be confused with NMS. Simvastatin was ceased with rapid decrease in CK level and resolution of symptoms. This case highlights the importance of considering other diagnoses in any patient presenting with a disturbance in conscious state, autonomic dysfunction, and an elevated CK level. Particularly in a patient with a history of NMS, a thorough medication history is essential to aid diagnosis and avoid confusion with presenting symptoms and medical history.

[Increase of serum procalcitonin levels during a neuroleptic malignant syndrome]. / Augmentation de la concentration sérique de la procalcitonine au cours d'un syndrome malin des neuroleptiques.

When fever occurs in a patient treated with a neuroleptic, the diagnosis of a neuroleptic malignant syndrome is difficult to differentiate to that of an infectious event. Among inflammation biomarkers of inflammation, serum procalcitonin levels increase both quickly and specifically during a bacterial infection. We report the first case of a neuroleptic malignant syndrome associated with a significant increase of serum procalcitonin levels, without concomitant septic syndrome. The neuroleptic malignant syndrome might be a non-infectious clinical situation associated with an increased serum procalcitonin concentration.

Atypical neuroleptic malignant syndrome with long-term clozapine.

Clozapine-induced neuroleptic malignant syndrome (NMS) may present differently from NMS associated with traditional antipsychotic agents, with fewer clinical features, particularly fewer extrapyramidal manifestations. The risk of developing NMS with clozapine does not appear dose-related. In half of cases, it occurs within 2 weeks of beginning clozapine therapy, but it can develop at any stage, especially with long-term use. We describe a patient who presented with atypical NMS after more than 10 years of clozapine treatment, and who was safely re-challenged with the same drug.

Postoperative neuroleptic malignant syndrome that occurred repeatedly in a patient with cerebral palsy.

A wide variety of neuroleptic agents are associated with neuroleptic malignant syndrome (NMS). However, the association between general anesthesia and NMS is uncertain. We report a case of a patient with cerebral palsy, who showed signs of NMS only after repeated general anesthesia. The patient received general anesthesia three times in a period of 9 months. The first anesthetic passed uneventfully. NMS symptoms were observed only after the second and third anesthetics. The NMS was effectively treated with IV dantrolene and the patient recovered on both occasions. Inhalational anesthetics, muscle relaxants and fentanyl were suspected as possible triggering factors for NMS. After examining the three anesthesia records and previous publications, we surmized that a nondepolarizing muscle relaxant was associated with NMS in this patient.

Cardiac involvement in malignant syndrome in Parkinson's disease.

Little is known about cardiac abnormalities in neuroleptic malignant syndrome (NMS) in Parkinson's disease (PD), although high levels of serum creatine kinase (CK) suggest the presence of cardiac involvement. We have also been aware of elevated serum myosin light chain I (MLCI) in these patients with no clear evidence of an acute coronary syndrome. To evaluate cardiac involvement in NMS in PD, we recorded the electrocardiogram (ECG) and measured serum MLCI and CK-MB levels. Plasma levels of noradrenaline and adrenaline were also determined. The patients were classified based on the in-hospital outcome into 55 survivors and 5 nonsurvivors. Age- and gender-matched PD patients without NMS served as controls (n = 51). All patients had high serum concentrations of CK-MB and MLCI. The mean values of CK, CK-MB, MLCI, adrenaline and noradrenaline were higher in both patient groups as compared to control subjects, and the values in nonsurvivors were significantly higher than those in survivors. A positive correlation was observed between serum MLCI and CK levels (p < 0.01), and between serum MLCI levels and plasma noradrenaline concentrations (p < 0.01). ECG abnormalities such as prolonged QTc interval, abnormal Q wave, ST elevation and T wave inversion were observed in all nonsurvivors and 32 (58.2%) survivors. We conclude that myocardial involvement is common in patients with NMS even when they have no symptoms suggestive of myocardial injury, and MLCI and CK-MB as well as ECG are useful indicators of mortality.