Neuroleptic Malignant Syndrome

The patient is a 50-year-old male who presented to the emergency department accompanied by his mother, who served as the primary historian due to the patient’s limited ability to provide history. The emergency physician documented that the mother reported: Acute drooling Muscle stiffness Onset of symptoms earlier that same day New medications initiated three days prior for difficulty sleeping The specific medications were not identified or documented. Vital Signs Heart rate: 110 bpm Respiratory rate: 18/min Blood pressure: 125/81 mmHg Temperature not documented Physical Examination Generalized muscle stiffness Patient described as sedated Laboratory Findings Creatine kinase: 1080 U/L (reference 20–180) BUN: 28 mg/dL (reference 6–20) BUN/Creatinine ratio: 30 (reference 10–20) Mild electrolyte abnormalities CBC without clinically significant abnormalities Medical Analysis Significance of Findings The combination of acute neuromuscular rigidity, altered mental status, autonomic abnormality (tachycardia), elevated CK, and recent initiation of medications is highly suggestive of neuroleptic malignant syndrome. Importantly, Absence of documented fever does not exclude NMS, particularly early in its course CK elevation above 1,000 U/L in this clinical context is abnormal and concerning for muscle injury due to sustained rigidity Reliance on a surrogate historian underscores the presence of altered mental status Standard of Care The standard of care for an emergency physician evaluating a patient with this presentation includes obtaining and documenting a complete medication history, especially recently initiated drugs Including neuroleptic malignant syndrome high in the differential diagnosis Monitoring core temperature and autonomic status, initiating aggressive IV hydration, discontinuing suspected offending agents, admitting the patient for close monitoring, frequently at an ICU level Considering pharmacologic therapy if symptoms worsen Breach of Standard of Care In this case, the emergency physician failed to identify and document recent medication exposure despite explicit reporting, failed to recognize or consider neuroleptic malignant syndrome, failed to initiate appropriate diagnostic evaluation or treatment for a known medical emergency, failed to appreciate the significance of markedly elevated creatine kinase in the setting of rigidity. These failures represent deviations from accepted emergency medicine standards of care. Causation As a direct result of these deviations, the offending medication(s) were not discontinued, supportive measures to prevent progression of disease were not initiated, the patient was exposed to a foreseeable risk of clinical deterioration, including rhabdomyolysis, renal failure, hyperthermia, and death. Early recognition and treatment of NMS are known to significantly reduce morbidity and mortality. Expert Opinion It is my expert opinion, to a reasonable degree of medical certainty, that the patient’s presentation was consistent with early neuroleptic malignant syndrome. Neuroleptic malignant syndrome should have been suspected and evaluated The emergency physician deviated from the standard of care. This deviation constituted a missed medical emergency. The patient was exposed to avoidable and unnecessary risk of harm. Conclusions This case represents a missed diagnosis of neuroleptic malignant syndrome at a critical early stage, when timely intervention could have prevented progression and serious complications. The failure to recognize and act upon classic clinical warning signs represents a breach of the standard of care in emergency medicine.

As a direct result of these deviations, the offending medication(s) were not discontinued, supportive measures to prevent progression of disease were not initiated, the patient was exposed to a foreseeable risk of clinical deterioration, including rhabdomyolysis, renal failure, hyperthermia, and death. Early recognition and treatment of NMS are known to significantly reduce morbidity and mortality.

There is more information that is needed to come to a complete conclusion. We need to know further details about recent medication changes, signs and symptoms upon presentation and time course of symptoms in the emergency department. Regardless, the presenting symptoms do appear consistent with early NMS, noting symptoms improved after the adminstration of benzos.

The patient developed worsening symptoms over the following days, due to the ongoing NMS. In order to make a definitive statement about the potential causation, more information is needed from records including medication dosing during that time, whether they filled valium prescription, return instructions, etc.

This patient on initial visit, did NOT have altered mental status, fever, or a change in dose or initiation of new meds. So this is an UNusual presentation of a RARE disease. Its not SOC for a ER MD to be able to diagnose unusual presentations of a rare disease. There is documentation of improvement. And the patient did come back when symptoms reoccurred or worsened, as likely instructed.

There is nothing the ER MD did to cause the NMS. They did not initiate or alter dose. And they recommended follow up with PCP who had the opportunity to stop meds if this was obvious. However, as stated above, this was not clear cut. The rare cases of NMS seen do not present so subtle.

The chief complaint in this case is stiffness after initiation of psychiatric medications. Stiffness following the start of psychotropic medications should always raise concern for medication-related adverse effects, including extrapyramidal symptoms such as acute dystonia, akathisia, drug-induced parkinsonism, or tardive dyskinesia, as well as more emergent conditions such as neuroleptic malignant syndrome (NMS) or serotonin syndrome. This presentation should prompt careful review of the patient’s current medications, assessment for possible overdose, and evaluation for adverse interactions related to combination pharmacotherapy. The medications listed in the EMR include Risperidone, an atypical antipsychotic with dopamine receptor antagonism. Although atypical antipsychotics generally carry a lower risk of NMS compared with older “typical” antipsychotics, they are still well-recognized causes of NMS. Classic features of NMS include fever/hyperthermia (notably, the patient’s temperature is absent from the documented vital signs), severe rigidity including “lead-pipe” rigidity, altered mental status, autonomic instability such as tachycardia (which may explain the patient’s initial heart rate of 110), labile blood pressure, diaphoresis, and elevated CK with rhabdomyolysis. Importantly, diaphoresis may have been less apparent or masked by the anticholinergic effects of Artane, which can complicate the clinical presentation of NMS. Additionally, the patient reportedly had recently been started on a medication three days earlier for difficulty sleeping, which was likely Trazodone, a medication commonly prescribed for insomnia. The combination of trazodone with Venlafaxine could increase the risk of serotonin syndrome. However, serotonin syndrome classically presents as a more hyperkinetic syndrome characterized by clonus, hyperreflexia, and tremor, whereas NMS more commonly presents with rigidity, bradykinesia, and generalized stiffness, which appears more consistent with this patient’s presentation. Furthermore, laboratory evaluation demonstrated an elevated CK level concerning for rhabdomyolysis, further increasing concern for NMS. The patient received intravenous fluids and benzodiazepine therapy, specifically diazepam (Valium), both of which are components of supportive management for NMS. Following treatment, documentation at 17:27 noted that the patient had “greatly improved” and was “able to stand up and walk unassisted,” suggesting at least partial response to therapy. The patient was ultimately diagnosed with non-traumatic rhabdomyolysis and adverse drug effect, diagnoses which themselves raise concern for early or evolving NMS. In that context, discharge from the emergency department would be concerning, particularly given that there does not appear to have been any modification or discontinuation of the medication most likely contributing to the presentation, namely risperidone. At the same time, abrupt cessation of risperidone may increase the risk of psychiatric decompensation or psychotic relapse. Accordingly, continued inpatient observation with psychiatric consultation after medical stabilization would have been reasonable to ensure appropriate medication adjustment, dosage reassessment, or consideration of alternative therapies prior to discharge.

The patient’s presentation was concerning for an early medication-related adverse reaction, most notably possible evolving neuroleptic malignant syndrome (NMS), evidenced by stiffness/rigidity, tachycardia, and elevated CK/rhabdomyolysis. Failure to adequately recognize, and appropriately manage this condition, including consideration of admission and medication adjustment, may have resulted in progression of the patient’s condition and exposed the patient to significant risk of further morbidity.

Patient symptomatically improved. No clear connection between condition at time of discharge and time of return. Patient should have been instructed to withhold venlafaxine and possible other meds. Treating prescriber should have been made aware of the potential ASAP.

Four days elapsed between the initial visit and the return visit. If the patient was instructed properly, to withhold meds as above, and took them anyway or if patient ingested more medication than appropriate, then the proximate cause of injury is not with the original discharge. In this case, the patients condition at discharge seems markedly improved, but we don't have enough information to make a causality statement.