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olanzepine induced neurolept malignant syndrome in a case of multiple sclerosis

Case Report Open Access
Deepak Hanumanthaiah* and Kumar Ramanathan
Anaesthesia and Intensive Care, Cork University Hospital, Cork, Ireland
*Corresponding author: Deepak Hanumanthaiah
Anaesthesia and Intensive Care
Cork University Hospital
Cork, Ireland
E-mail: drdeepakhrh@yahoo.co.in
 
Received November 30, 2011; Published October 29, 2012
 
Citation: Hanumanthaiah D, Ramanathan K (2012) Olanzepine Induced Neurolept Malignant Syndrome in a Case of Multiple Sclerosis. 1:412. doi:10.4172/scientificreports.412
 
Copyright: © 2012 Hanumanthaiah D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
Abstract
 
Suspicion of narcoleptic malignant syndrome (NMS) is a frequent cause of emergent psychiatric consultation. Despite early recognition, NMS has remained a syndrome that causes high rates of morbidity and mortality. A 25-year-old male with multiple sclerosis presented to the A&E with ataxia. He was started on steroids. On the third day, he became tearful and anxious. A diagnosis of multiple sclerosis induces psychosis was made and he was started on olanzepine 2.5 mg BD. On the sixth day patient was tachpneic and had tachycardia. Temperature recorded in the axilla was 45 C. Patient was intubated and electively ventilated. A diagnosis of NMS was made and treated accordingly. There is little evidence to show that low dose olazepine causes NMS. The relapse rate of NMS is nearly 80%. ECT has been used as an alternative method for treatment of psychosis in patients with increased risk of NMS with medications.
 
Keywords
 
Neurolept malignant syndrome; Multiple sclerosis
 
Introduction
 
Suspicion of Narcoleptic Malignant Syndrome (NMS) is a frequent cause of emergent psychiatric consultation. This uncommon syndrome, characterized by muscular rigidity, autonomic instability, hyperthermia, and mental status changes, has been associated with conventional dopamine D2 receptor antagonist treatments such as haloperidol or fluphenazine. Despite early recognition, NMS has remained a syndrome that causes high rates of morbidity and mortality [ 1]. A review in 2009 suggests that, in general, NMS associated with atypical antipsychotic drugs manifests in a typical manner. One notable exception is clozapine-induced NMS, which appears less likely to manifest with extra pyramidal features, including rigidity and tremor [ 2]. A significant incidence and prevalence of psychological disorders in Multiple Sclerosis (MS) has been reported. Their underlying mechanisms and the extent, to which they are reactive to psychosocial factors or symptoms of the pathological process itself, remain unclear. It is concluded that psychiatric onset of MS may occur in up to 1% of patients, and that in previously healthy persons with acute psychotic disorder even the slightest neurological abnormality justifies a cranial MRI examination.
 
Case Report
 
A 25 year old man, with a background history of multiple sclerosis in remission for two years came to the A&E with weakness in his right arm and leg for six hours. He also had ataxia. There was no focal/urinary incontinence or visual disturbances. He was started on methyprednisolone 1 gram. On the third day, the patient had jerky movements and shivering. He also had dysarthria, past pointing and blurring of vision and nystagmus. He was very anxious, tearful, apprehensive diagnosis of psychosis was made, and the patient was started on olanzepine 2.5 mg BD. He also had a lumbar puncture done for nystagmus and ataxia. On the sixth day patient was tachpneic and had tachycardia. He was very drowsy. Temperature recorded in the axilla was 45°C. Blood tests revealed an increased creatinine kinase levels. Patient was intubated and electively ventilated. His CK levels continued to rise. Levels of AST, ALT and LDH were also elevated. His urine output decreased with increasing levels of creatinine and urea. Haemodialysis was started. The temperature was measured continuously via a rectal probe. At all times temperature was above 40°C persistently. A diagnosis of Neurolept malignant hyperthermia was made. Arterial lines and a central line were inserted. Patient was well hydrated. Active cooling measures were initiated. Bloods were closely monitored for evidence of DIC and electrolyte imbalance. Anti pyretic was started. patient was started on bromocryptine 5 mg NG TDS, Dantrolene 200 mg IV QDS,baclofen 10 mg tds and clonidine 100 micrograms BD. The symptoms of NMS started coming down and the patient made a complete recovery in two days. MRI of the brain revealed extensive plaques in brain stem and swelling of the brain. A diagnosis of multiple sclerosis with superimposed acute demyelinating encephalomyelitis was made. The patient was extubated three days after he was intubated.
 
Discussion
 
Neuroleptic Malignant Syndrome (NMS) refers to the combination of hyperthermia, rigidity, and autonomic dysregulation that can occur as a serious complication of the use of antipsychotic drugs. Delay first used the term in 1960, after observing patients treated with high-potency antipsychotics [3] the syndrome can occur after any duration of treatment, although two thirds of cases occur within the first week. The frequency has been variably reported as 0.07-2.2% of patients taking neuroleptics [4]. Data largely come from case control studies rather than prospective randomized trials. The serotonin syndrome is very similar to neuroleptic malignant syndrome. The triad of (1) altered mental status, (2) autonomic dysfunction, and (3) neuromuscular abnormalities that occurs on exposure to serotonergic agents characterizes the serotonin syndrome. Selective serotonin reuptake inhibitors (SSRIs) are the most frequently used medications in this class. The serotonin syndrome can be distinguished from neuroleptic malignant syndrome in most cases by a detailed history of medication use with particular attention to recent dosage changes and the absence of severe rigidity [5]. Neuroleptic malignant syndrome pathophysiology is largely speculative. Neuroleptic drugs block dopaminergic receptors, creating a functional dopamine-deficiency state. Dopaminergic receptor blockade in the substantial nigra causes muscle rigidity and alters thermoregulation in the hypothalamus. Increased heat production from muscle rigidity causes fever, impaired heat dissipation (by reducing cutaneous vasodilatation or by sweating), and possibly a higher core temperature set point in the hypothalamus [ 6].
 
Although rhabdomyolysis is a rare side effect (<1%) of olanzapine, this adverse event should be evoked when a patient with olanzapine presents with muscle pain, unexplained fatigue or weakness. Prompt dosage of CK should be performed. However, it remains uncertain whether a mild and asymptomatic muscle enzyme increase without any metabolic disorder requires the discontinuation of olanzapine therapy [ 7].
 
An algorithm has been suggested to treat both NMS and seronergic syndrome, as it’s not possible to differentiate them sometimes. The suggested algorithm includes: 1) Supportive care and withdrawal of all potentially offending agents; 2) Laboratory evaluation with prompt initiation of treatment for both disorders—cyproheptadine for SS and dantrolene for NMS; 3) Do not use bromocriptine (contraindicated in SS) or chlorpromazine (contraindicated in NMS) initially; 4) Add bromocriptine when serotonergic agent has long half-life) [8]. The efficacy of using dantrolene as a mode of treatment in NMS has been questioned [9].
 
In our case, the patient had psychotic features, which is commonly treated with olanzepine. Though there have been many reports of NMS with high dose olanzepine [9], there is little evidence to show that low dose olazepine causes NMS. The other feature in this case was the time taken for the onset of NMS. Reports normally mention weeks to months for NMS to set in after initiating olanzepine, in our case the symptoms started after 3 days after starting low dose olanzepine. The most important factor which predicts mortality in a case of NMS is onset of renal failure. Our case also have renal failure but prompt initiation of renal replacement therapy was life saving. The most important cause of renal failure is myoglobinuria which leads to acute tubular necrosis. The relapse rate of NMS is nearly 80%.ECT has been used as an alternative method for treatment of psychosis in patients with increased risk of NMS with medications [10].
 
 
References