Neuroleptic malignant syndrome with acute renal failure associated with rhabdomyolysis: a case report

Neuroleptic malignant syndrome is a rare, life-threatening neurologic emergency characterized by fever, rigidity, autonomic instability, mental status changes, and an elevated creatine kinase level. It often occurs shortly after the initiation of neuroleptic treatment, or after a dose increase. The management of patients with NMS is based upon clinical severity and includes supportive care and withdrawal of antipsychotic agents and agents like bromocriptine and dan-trolene. Complications include acute renal failure associated with rhabdomyolysis, respiratory failure


Introduction
NMS is a life-threatening neurologic emergency associated with the use of dopamine antagonists, and less commonly with dopamine agonist withdrawal [1,2].First-generation antipsychotic agents (e.g., haloperidol, fluphenazine) are most commonly implicated but NMS can occur with any antipsychotic agent including second-generation drugs ( e.g., clozapine, risperidone, olanzapine) and also with antiemetic drugs (e.g., metoclopramide, promethazine, and levosulpride).Incidence rates for NMS range from 0.02 to 3% among patients taking antipsychotics [3].Case-control studies implicate recent or rapid dose escalation, a switch from one agent to another, and parenteral administration as risk factors [4].Clinical features include tetrad of typical symptoms including fever (typically above 38 °C), rigidity (generalized, lead pipe rigidity), mental status changes, and dysautonomia manifesting as tachycardia, labile blood pressure, tachypnea, arrhythmias.Elevated creatine kinase, typically more than 1000 international units /L.An international multispeciality consensus group published diagnostic criteria for NMS in 2011 [3].Differential diagnoses include meningitis, encephalitis, serotonin syndrome, malignant hyperthermia, malignant catatonia, and other drug-related syndromes (withdrawal of intrathecal baclofen therapy, acute intoxication with cocaine, MDMA, etc.) A case is described that highlights the challenges met in making the diagnosis, treatment, and final outcome of the patient.
A firm diagnosis of NMS with AKI with rhabdomyolysis was made.The patient was taken for hemodialysis on the same day of admission in view of AKI due to rhabdomyolysis, dialysis was done for 3 h with 1500 ml ultrafiltration.The patient was kept in the intensive care unit.Tablet Bromocriptine was started (2.5 mg TDS) which was tapered over the course of 14 days and then stopped.For her agitation Inj.Lorazepam in the dose 1 mg iv/im every 6 h was given.Inj.Diazepam (10 mg i/v slowly) single dose was also helpful.The patient underwent regular hemodialysis for her ATN due to rhabdomyolysis; however, her other lab parameters showed a decreasing trend (Table 1).After a few days, she developed a focal seizure in one episode.NCCT Head (Fig. 3) was repeated and subsequently, an MRI brain (Fig. 4) was done which revealed increased hypodense areas in B/L cerebral and cerebellar hemispheres.MRI Brain was suggestive of encephalopathy.Her GCS dropped in view of the same.We continued the supportive therapy and she  Fig. 2 NCCT head on admission [5] has started steroids (Inj Dexamethasone 4 mg i/v, 6hrly and gradually tapered).The patient's clinical status and GCS improved significantly afterward and she was discharged in a hemodynamically stable state after 20 days.

Discussion
This case illustrates one of the many clinical presentations possible with the depot use of potent antipsychotic drugs and the many difficulties faced during her treatment due to complications of NMS.The diagnosis of NMS was established based on the typical history of depot drug administration and other characteristic features including markedly raised serum CPK levels, worsening mental status, muscle rigidity, and diaphoresis.Our patient developed rhabdomyolysis and landed into acute kidney injury.Even with more sensitive criteria, a high index of suspicion is still necessary for clinicians to make a prompt diagnosis based on clinical history [6].

Comments
Neuroleptic malignant syndrome (NMS) is a lifethreatening neurologic emergency associated with the use of antipsychotic (neuroleptic) agents and is characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia.Incidence rates for NMS range from 0.02 to 3% among patients taking antipsychotic agents.While most patients with NMS are young adults, the syndrome has been described in all age groups from 9 to 78 years.In Fig. 3 Repeat NCCT head [5] most studies, males outnumber females twofold.This was a rare case where a female was affected with many complications of NMS.A rapid loading schedule, especially with potent neuroleptics like haloperidol is considered to be the principal contributing factor in the development of NMS, by causing a sudden and massive down-regulation of dopaminergic transmission.This could have occurred in our patient [7].

Message
Polypharmacy in the case of neuropsychiatric diseases should always be avoided to prevent dreadful conditions like NMS with ARF leading to rhabdomyolysis.

Table 1
Laboratory investigations