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Year : 2007  |  Volume : 55  |  Issue : 2  |  Page : 166-168

The neuroleptic malignant syndrome: A report of 14 cases from North India

Department of Neurology, SMS Medical College and Attached Hospitals, Jaipur, India

Date of Acceptance20-Mar-2007

Correspondence Address:
A Panagariya
7, Raj Niketan, Moti Doongri Road, Jaipur - 302 004
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.32793

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 » Abstract 

Neuroleptic malignant syndrome (NMS) is a rare, life-threatening but potentially treatable condition. This study was performed to investigate the clinical spectrum, antecedent events and outcome of NMS patients admitted in the Neurology department of a large teaching hospital of North India. Fourteen cases of NMS were taken after a thorough search during a three-year period (May 2000 to April 2003). The Incidence of NMS was 1.40/ 1000 patients treated with neuroleptics and mortality rate was 14.28%. Amongst the neuroleptics Haloperidol (parenteral) was implicated as a most common drug for NMS in 57% of patients. An association with coexisting precipitating illness was clearly recorded in 71.4% patients. All the recorded patients of NMS received 500-700 mg CPZ equivalent/day of neuroleptics. NMS as an indiosyncratic phenomenon was noticed in 28% patients. 85.7% responded to dopaminergic drugs along with supportive treatment and showed partial or complete recovery within 7-14 days. In those with partial recovery residual deficits included Parkinsonian features, depression and diaphoresis in a small percentage of patients.

Keywords: Fever, neuroleptic malignant syndrome, neuroleptics

How to cite this article:
Panagariya A, Sharma B, Singh R, Agarwal V, Dev A. The neuroleptic malignant syndrome: A report of 14 cases from North India. Neurol India 2007;55:166-8

How to cite this URL:
Panagariya A, Sharma B, Singh R, Agarwal V, Dev A. The neuroleptic malignant syndrome: A report of 14 cases from North India. Neurol India [serial online] 2007 [cited 2023 Feb 6];55:166-8. Available from: https://www.neurologyindia.com/text.asp?2007/55/2/166/32793

Neuroleptic malignant syndrome (NMS) has attracted widespread attention among neurologists and psychiatrists in the last few years. Over the last decade, 1000 cases of NMS have been reported.[1] It is a potentially life-threatening complication of neuroleptic drugs. The frequency and mortality of NMS among neuroleptic drug users has been recorded around 0.5-2.4% and 4-30%[2] respectively. This disorder is recognized as a hypodopaminergic state characterized by muscle rigidity, hyperthermia, altered sensorium, autonomic instability and elevated serum creatinine phosphokinase (CPK) levels; the details of this clinical syndrome still remain hazy.[1] Many diagnostic criteria have been proposed, but the lack of universally accepted criteria is perhaps the most serious drawback for study of this condition.

Much of the understanding of this disorder is based on review and case series from the western countries.[3] Noticeable among the reports from other countries is a prospective study from China[4] which showed fluphenazine deconoate as the major risk factor. There have been few individual case reports[5],[6] short series[7],[8] and reviews[9] from India but no systematic data is available till date except those given by Chopra et al .[8]

 » Observations and Discussion Top

This study was conducted at the SMS Medical College Hospital, a large teaching hospital of North India. All patients with symptom complex suggestive of NMS were analyzed in detail between the year 2001-2003 and a total of 14 patients were confirmed to have NMS on the basis of Caroff and Mann criteria[2] [Table - 1] and after excluding various NMS-simulating diseases (heat stroke, acute anticholinergic syndrome, catatonia, status epilepticus, encephalitis, etc.). A detailed analysis of these cases was made including evaluation of coexistent systemic or organic brain syndromes.

The purpose of this study is to highlight clinical and prognostic aspects of NMS and to increase awareness among physicians, neurologists and psychiatrists about this under-recognized complication of neuroleptic medication, which if diagnosed in time can be treated successfully.

Characteristics of patients who developed NMS are summarized in [Table - 2],[Table - 3]. The incidence rate obtained was 1.40/1000 cases treated with neuroleptics, a finding matching with the retrospective study by Chopra et al ,[8] although relatively low incidence has been documented in prospective studies.[10] A comparatively higher incidence in the present prospective study could be because of the inclusion of spectrum concept of NMS in the study, including incipient, mild cases to profoundly ill patients. The majority of patients who developed NMS were male (64.28%) and were below 40 years of age (85.7%). Similar findings were noticed early by Chopra et al .[8] Most of the patients were given high potency neuroleptics (HPD, CPZ) for the first time for different reasons by parenteral route as earlier noticed by Keck et al .[10] Haloperidol was the most common drug incriminated. Idiosyncratic phenomenon was noticed in 28% cases, an observation earlier documented in a short series.[11] Fifty-six per cent (9 out of 14) of our patients showed moderate to severe dehydration. Presence of dehydration predisposes to NMS because the decreased blood volume induces peripheral vasoconstriction which impairs heat dissipation. In our series, five patients of encephalitis developed classical features of NMS. Such association has been rarely noticed earlier. Neuroleptic malignant syndrome is known to occur as a result of a hypodopaminergic state caused by a neuroleptic. A relative hydopaminergic state in encephalitic illness can be thought of, which might have led to the association of encephalitic illness with NMS.[12],[13] One patient developed NMS on the background of alcoholism; it could be as a result of increased susceptibility of the skeletal muscle to neuroleptics under the effect of alcohol as postulated in the literature.[1] Neuroleptic malignant syndrome is said to be a diagnosis of exclusion but clinicians should not be reluctant to make a diagnosis of NMS in the presence of a coexistent disease/infection. The findings also imply that in the presence of organic brain syndrome, neuroleptics where especially typical high potency ones should be used cautiously. Clinicians should have a high index of suspicion in such cases so as to diagnose NMS in the early stage. Although newer/ atypical neuroleptics have been introduced to avoid this dreaded complication they have also been infrequently incriminated in causation of NMS in a few case reports.[14],[15] Like some previous studies the time range of neuroleptic treatment was one to three days prior to development of NMS more so if high potency neuroleptics were administered for the first time. In addition, antiemetic drug Metaclopromide ingestion preceded the illness in four (28%) patients as earlier pointed out by Nehru et al .[9]

Fever, altered sensorium and rigidity were the cardinal features of all cases, a finding matching with earlier studies. However, oromandibular dyskinesia (7%), myokymia (7%) and seizures (14%) were some unusual observations recorded in the present study.

Muscle enzyme creatinine phosphokinase (CPK) levels were elevated above the normal limit (0-200IU/L) in 85.7% of cases. Specific neurological investigations like CSF, CT or MRI could not point to any significant observation in the majority of cases and were done to exclude other differential diagnoses. However, acute cerebral venous thrombosis in single patients could be noticed as a component of their coexisting organic brain syndrome apart from NMS.

Opinion regarding the role of CPK in diagnosing NMS has faced a lot of controversy in the recent past. In one Indian report of three cases of NMS, peak serum CPK values were either normal or marginally raised.[13] However, in the present study 12 out of 14 had raised CPK values which was consistent with earlier reviews.[1] Eighty-six per cent had raised levels of LDH, SGOT and SGPT but the rise was less dramatic than creatinine phosphokinase (CPK) levels (500-500IU/L) an observation made earlier in another study.[1] Leucocytosis was noticed in all cases in the present study is contrast to its occurrence in 75% cases in earlier studies.

A fatal outcome (mortality) occurred in two (14%) patients at an average of three to five days after developing NMS and was reported to be due to cardiac arrest in one and aspiration pneumonitis in the other patient. Recovery was noticed in 12 (85.7%) patients (although partial in 21% and complete in the rest of the patients). Residual symptoms and signs like Parkinsonian features (three), depression (one) and diaphoresis (2%) were noticed on subsequent follow-up.

Regarding treatment till date dantrolene sodium and Bromocriptine (in refractory cases - electroconvulsive therapy) have been tried, in addition to withdrawal of offending drug. The emphasis should also be laid on avoiding dehydration and proper management of underlying organic brain syndrome.

In the present study the offending drugs i.e. neuroleptics and antiemetics were stopped immediately as soon as NMS was suspected clinically. After confirmation of the diagnosis dopamenergic agonist Bromocriptine in a build up dosage (after 5-20 mg/day) along with supportive treatment such as fever reduction, hydration and maintenance of nutrition was given to all the patients at the earliest. Recovery was noticed in 12 (85.7%) patients, As compared to recovery documented in 75-82% of cases elsewhere. Inclusion of relatively less severe cases of the spectrum of NMS in our study might have caused higher percentage of recovery. Recovery was complete in the majority of cases (79%) and partial in 21% of cases. Residual symptoms and signs like Parkinsonian features (three patients), depression (one patient) and diaphoresis (two patients) were noticed on subsequent follow-up. Residual extrapyramidal features have been described in other studies as well.[4]

 » References Top

1.Adnet P, Lestavel P, Krivosic R. Horber - Neuroleptic malignant syndrome. Br J Anaesthesia 1985;1:129-35.  Back to cited text no. 1    
2.Caroff SN. The neuroleptic malignant syndrome. J Clin Psychiatry 1980;41:79-83.  Back to cited text no. 2  [PUBMED]  
3.Shalev A, Hermesh H, Munitz M. Mortality from Neuroleptic malignant syndrome. J Clin Psychiatry 1989;50:18-25.  Back to cited text no. 3    
4.Deng MZ, Chen GQ, Phillips MR. Neuroleptic malignant syndrome in 12 of 9,792 Chinese inpatients exposed to neuroleptics. A prospective study. Am J Psychiatry 1990;147:1149-55.  Back to cited text no. 4    
5.Khandelwal V, Gupta N, Agarwal A, Goyal RK. Tricyclic antidepressants overdose presenting as neuroleptic malignant syndrome. J Assoc Physicians India 2002;50:614.  Back to cited text no. 5    
6.Yeolekar ME, Gupta H. Persistent fever in a case of typhoid - An unusual cause of neuroleptic malignant syndrome. J Assoc Physicians India 2001;49:296.  Back to cited text no. 6    
7.Kurien T, Rajeev KK. Management of neuroleptic malignant syndrome - A series of 8 cases. J Assoc Physicians India 1993;41:91-3.  Back to cited text no. 7    
8.Chopra MP, Prakash SS, Raguram R. The neuroleptic malignant syndrome: An Indian experience. Compr Psychiatry 1999;40:19-23.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Nehru R, Grover A, Aggarwal V, Gera P, Gupta editors. Neuroleptic malignant syndrome. Manual of medical emergencies. MM Health Care Pvt Ltd: Delhi; 1997. p. 480-3.  Back to cited text no. 9    
10.Keck PE, Pape HG, Mc Elroy SL. Declining frequency of neuroleptic malignant syndrome in a hospital population. Am J Psychiatry 1991;148:880-2.  Back to cited text no. 10    
11.Peiris DT, Kuruppuarachchi K, Weerasena LP, Seneviratne SL, Tilakaratna YT, De Silva HJ, et al . Neuroleptic malignant syndrome without fever: A report of three cases. J Neurol Neurosurg Psychiatry 2000;69:277-8.   Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12. Misra UK, Kalita J, Pandey S, Khanna VK, Babu GN. Cerebrospinal fluid catecholamine levels in Japanese encephalitis patients with movement disorders. Neurochem Res 2005;30:1075-8.  Back to cited text no. 12    
13.Hillis RE, Lee DA. Viral encephalitis complicated by neuroleptic malignant syndrome in a 7- year-old girl. Pediatr Emerg Care 2003;19:99-100.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Bottlender R, Jager M, Hofschuster E, Dobmeier P, Moller HJ. Neuroleptic malignant syndrome due to atypical neuroleptic three episodes in one patient. Pharmacopsychiatry 2002;35:119-21.  Back to cited text no. 14    
15.Shukla I, Singh O, Rehman N. Neuroleptic malignant syndrome in critical care unit. Indian J Crit Care Med 2006;10:50-2.  Back to cited text no. 15    


  [Table - 1], [Table - 2], [Table - 3]

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