Episodes Of Neuroleptic Malignant Syndrome Research Articles

Risk of Neuroleptic Malignant Syndrome with Vesicular Monoamine Transporter Inhibitors.

ObjectiveVesicular monoamine transporter-2 (VMAT2) inhibitors have been proven to be effective for the treatment of tardive dyskinesia and their use is likely to increase. The evidence base of published clinical reports was reviewed to evaluate the possible risk of neuroleptic malignant syndrome (NMS) with these drugs.MethodsPubmed, Embase, Web of Science and PsycINFO databases were queried for all years using terms for “neuroleptic malignant syndrome”, “hyperthermia” AND “vesicular monoamine transporter inhibitors”, “reserpine”, “tetrabenazine”, “valbenazine” or “deutetrabenazine”ResultsThirteen clinical cases, ten of which involved tetrabenazine, were identified in which VMAT2 inhibitors were prescribed in patients with current or past NMS episodes. In most cases, the association was confounded by limited reporting of clinical data, variable temporal correlation with VMAT2 inhibitors, polypharmacy with antipsychotics, and uncertain differential diagnoses.ConclusionWhile rare cases of NMS meeting consensus criteria have been reported primarily with tetrabenazine, the risk with recently developed VMAT2 inhibitors may be even less. Evidence of causality of NMS with VMAT2 inhibitors is confounded by concomitant treatment with antipsychotics and diagnostic uncertainties in patients susceptible to basal ganglia dysfunction. Nevertheless, clinicians should remain vigilant for early signs of NMS in all patients treated with any drugs that affect brain dopamine activity.

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 Bakırköy 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.

Multiple episodes of NMS: overlap with malignant catatonia

There is ongoing debate in the literature as to whether neuroleptic malignant syndrome (NMS) and malignant catatonia are distinct clinical entities or illnesses on the same spectrum. Here, Drs Hardy and Evans present a case which puts forward arguments for both sides of the debate and raises questions regarding further management of psychosis in patients who develop multiple episodes of NMS.

Neuroleptic Malignant Syndrome Associated with the Use of Prochlorperazine in a Patient with a Recent History of Antipsychotic-Induced Neuroleptic Malignant Syndrome

To describe a case of neuroleptic malignant syndrome (NMS) associated with the use of prochlorperazine in a patient recently hospitalized for NMS secondary to olanzapine. A 28-year-old African American male with a history of schizophrenia was hospitalized 22 days prior to the current admission for an episode of olanzapine-induced NMS. The patient was discharged from our hospital to an outside psychiatric facility. At this facility, the patient developed nausea and was given 2 doses (unknown amount and route) of prochlorperazine. Over the next 24 hours, the patient exhibited signs and symptoms of NMS including fever, agitation, and muscle rigidity. He was transported to the emergency department and became increasingly agitated. Upon admission, the patient was hyperthermic (rectal temperature 39 °C) and tachycardic (heart rate 138 beats/min), with an elevated white blood cell count of 13.5 × 10(3)/μL, creatine kinase 431 units/L, serum sodium 150 mEq/L, blood urea nitrogen 25 mg/dL, and creatinine 1.1 mg/dL. A diagnosis of NMS was speculated and infectious causes were excluded. The patient was treated with aggressive fluid resuscitation and rapid cooling measures, as well as bromocriptine and lorazepam. Cooling measures were used for 48 hours, during which time the creatine kinase, white blood cell count, sodium, blood urea nitrogen, and creatinine gradually normalized. The patient was discharged to a psychiatry facility with a treatment regimen of oxcarbazepine 600 mg twice daily, lorazepam 2 mg 3 times daily, and clozapine 25 mg at bedtime, which was titrated over 2 months to 200 mg twice daily. There have been no further occurrences of NMS. The patient had all of the major characteristics of NMS with no other likely causative factors that may have contributed to his illness. Use of the Naranjo probability scale suggested that NMS was probably related to prochlorperazine. This case highlights the potential increased risk with the use of prochlorperazine in a patient with a history of olanzapine-induced NMS. NMS should be considered as a rare complication of therapy with antipsychotics and agents that alter dopamine activity, especially in patients with a history of the syndrome. Careful consideration should be given regarding the risks and benefits of using non-antipsychotic dopamine antagonists in patients with a history of antipsychotic-induced NMS.

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome (NMS) is a potentially fatal adverse event associated with the use of antipsychotics (AP). The objective of this study was to investigate the profile of cases of NMS and to compare our findings with those published in similar settings. A series of 18 consecutive patients with an established diagnosis of NMS was analyzed, gathering data on demography, symptoms and signs. Two thirds of all cases involved woman with a past medical history of psychiatric disorder receiving relatively high doses of AP. The signs and symptoms of NMS episodes were similar to those reported in other series and only one case had a fatal outcome, the remaining presenting complete recovery. As expected, more than two thirds of our cases were using classic AP (68%), however the clinical profile of these in comparison with those taking newer agent was similar. Newer AP also carry the potential for NMS.

Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome

Catatonic Variants, Hyperthermic Extrapyramidal Reactions, and Subtypes of Neuroleptic Malignant Syndrome

This case series study examines the hypothesis that neuroleptic malignant syndrome (NMS) is a heterogeneous condition including catatonic variants and non-catatonic pathological reactions to antipsychotics. Fourteen episodes of NMS were prospectively identified. Patients were examined for catatonia during the course of NMS. Close monitoring of catatonia episodes and suspected cases of evolving NMS for possible NMS development provided data on the pre-NMS clinical course. All NMS episodes received benzodiazepines. Episodes with catatonia diagnosed were compared with those without catatonia, noting their presentation, clinical course and responses to treatment. Concurrent catatonia was diagnosed in 9 episodes. In 6 of them antecedent catatonia progressed to NMS following antipsychotic exposure (NMS of antipsychotic-converted catatonia). In 3 episodes, a parkinsonian-catatonic syndrome with fever and autonomic abnormality developed in reaction to antipsychotics (NMS of antipsychotic-induced catatonia). Catatonia was not diagnosed in 5 during the longitudinal course of NMS. A severe extrapyramidal reaction to antipsychotics with associated delirium preceded all 5 episodes. Seven of the 9 NMS episodes with catatonia and none of the 5 without catatonia showed significant responses to benzodiazepines. The preliminary findings support the hypothesis that NMS is a heterogeneous condition including catatonic variants and non-catatonic hyperthermic extrapyramidal reactions to antipsychotics, differing in presentation, clinical course, and treatment responses.

Olanzapine‐Associated Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS) is a rare but potentially serious complication of neuroleptic drugs. It may vary in both presenting characteristics and severity. Several different criteria for diagnosis exist, and each differs from the others slightly. We describe a 66-year-old woman with chronic paranoid schizophrenia who was prescribed olanzapine along with several other psychiatric drugs and an antihypertensive drug. The patient displayed several characteristics of NMS during therapy with olanzapine, including fever, elevated creatine kinase level, leukocytosis, and mild muscle rigidity. When olanzapine was held, the signs and symptoms improved and then returned with rechallenge of olanzapine. For this reason, olanzapine was considered strongly associated with this patient's apparent NMS episode. The patient's beta-blocker therapy may have masked additional signs of NMS. In addition, the patient tolerated other neuroleptics that were started in the hospital after the suspected NMS episode. The variation among different diagnostic criteria makes this syndrome a challenging diagnosis at times, in particular when atypical antipsychotics are suspected as the causative agent.

Methylphenidate-Induced Neuroleptic Malignant Syndrome

Sir: Methylphenidate is a piperidine derivative, structurally related to amphetamines. It reaches peak blood concentration in 2 hours and has a short half-life of 1 to 2 hours. Its onset of action occurs shortly after dosing, and it can cause increased wakefulness, energy, alertness, and physical and mental performance. Its side effects include anorexia, weight loss, slow growth, insomnia, dysphoria, tics, and psychosis. There is a single case report of methylphenidate causing neuroleptic malignant syndrome (NMS) in a 1-year-old child with encephalomalacia.1 We report the first case of methylphenidate causing increased creatine kinase levels and possible neuroleptic malignant syndrome in a patient who had autistic disorder in the absence of any brain malformation. Case report. A 10-year-old African American boy with autistic disorder (DSM-IV criteria) was admitted in 2002 to the child psychiatry inpatient unit as a crisis intervention measure to stabilize his numerous behavioral problems. The behavior of the patient was characterized by constant fidgetiness, restlessness, kicking, biting, and spitting. He also was throwing things and trying to run away. The patient was started on treatment with risperidone and clonazepam without success—he spit out his medications. In view of the escalation of the patient's behavioral problems, intramuscular haloperidol and lorazepam were tried on an as-needed basis. After 2 injections each of haloperidol (5 mg) and lorazepam (2 mg) over 1 to 2 days, the patient had a dystonic reaction and was treated with diphenhydramine. However, after the patient received an additional 4 doses each of haloperidol (total of 20 mg) and lorazepam (total of 8 mg) by intramuscular injection over 2 days, he developed signs and symptoms suggestive of NMS, including fever, tachycardia, elevated white blood cell count, and creatine kinase (CK) levels elevated to over 8000 U/L. The patient was transferred to the pediatric intensive care unit and treated appropriately by stopping haloperidol and starting intravenous hydration and sedation. The patient was transferred back to the psychiatric unit after his CK level, showing a downward trend, had decreased to 2000 U/L. However, the behavioral problems in the form of aggression, spitting, and throwing things continued, and the patient was also constantly fidgety and restless. At this stage, a trial of methylphenidate was considered with the hope of decreasing the patient's restlessness and fidgetiness. After he received the first and only dose of methylphenidate, 5 mg, he was noted to be relatively calm and less fidgety. However, the patient subsequently developed a fever, and his CK level increased from 690 U/L at the time of methylphenidate administration to 1033 U/L 5 hours after methylphenidate administration. During this time, the patient was not agitated and not restrained and received no intramuscular injections that might explain the elevation of CK levels. One day after the administration of methylphenidate, the patient's fever subsided and his CK level dropped to 618 U/L and continued to drop further. No further doses of methylphenidate were administered. Neuroleptic malignant syndrome is a potentially life-threatening condition that presents with hyperthermia, mental status changes, oculogyric crisis, autonomic instability, and increased CK levels. Potential risk factors are previous episodes of NMS, psychomotor agitation, dehydration, rapid increase of neuroleptic medication, and parenteral routes of administration. Conventional and atypical antipsychotics have been implicated in its causation, as are any agents that possess dopaminergic antagonistic action. In the present, we do not know if the patient would have developed all the signs and symptoms of NMS if he had continued to receive methylphenidate. However, he certainly had a significant CK level elevation that was related to methylphenidate. Since elevated CK levels are seen in about 95% of patients with NMS,2 it is likely that he might have developed a full-blown NMS. It is possible that patients who have a propensity to develop NMS with antipsychotic medication are also likely to develop NMS with methylphenidate. Typically, NMS is caused by blockade of dopaminergic receptors. However, methylphenidate acts by inhibiting reuptake of dopamine, and therefore the mechanism by which it caused elevation of CK levels is not known. Prior to this report, there has been only 1 case report describing neuroleptic malignant syndrome following methylphenidate administration, and that was in a 1-year-old child with encephalomalacia.1 This is the first case of NMS in a person without brain malformation. Methylphenidate should be used with caution in patients who have had an adverse reaction to antipsychotics. We believe that further experience is required before we can come to a definite conclusion that methylphenidate indeed can cause NMS and also before we can determine the mechanism by which it does so.

Clozapine-Induced Neuroleptic Malignant Syndrome and Subdural Hematoma

Clozapine-Induced Neuroleptic Malignant Syndrome and Subdural Hematoma

Lebensbedrohliches malignes neuroleptisches Syndrom unter Olanzapin

The frequency of neuroleptic malignant syndrome (NMS) after clozapine or olanzapine is low and often of non-serious nature. A 49 year-old female patient developed NMS 12 days after olanzapine re-exposure. Olanzapine was stopped, the patient was transferred to an ICU and received a course of nine uni- and bilateral ECT treatments. This led to remission. 14 months earlier the patient had presented with a first severe NMS episode after haloperidol depot injection and 4 days after starting oral clozapine. Following the first NMS episode olanzapine (20 mg per day) was administered for 11 months without adverse effects.

Olanzapine-associated neuroleptic malignant syndrome

Neuroleptic malignant syndrome (NMS) is an uncommon but serious idiosyncratic reaction associated with antipsychotic medication. The purpose of this study was to reveal and analyze the clinical characteristics of the reported cases of NMS in patients given the novel antipsychotic olanzapine. A MEDLINE search related to olanzapine-induced NMS cases reported in the international literature was conducted. All cases were critically reviewed and examined against three different sets of NMS diagnostic criteria (DSM-IV, Addonizio, Levenson). The authors identified 17 cases of possible NMS associated with olanzapine. Ten of the reported NMS cases were definitely NMS meeting all three sets of criteria and three cases were probable NMS meeting two sets of criteria. Most of the patients exhibited a full-blown NMS. There were four definite NMS cases associated with olanzapine monotherapy. Three of them had concurrent serious physical illnesses and one had a previous NMS episode. Olanzapine can cause NMS, mainly in susceptible or predisposed patients.

Safety and efficacy of long-term low-dose clozapine aftercare treatment in a patient with learning difficulties who suffered from neuroleptic malignant syndrome

INTRODUCTION : Antipsychotic medication continues to be an essential component in the treatment of schizophrenia. Neuroleptic malignant syndrome (NMS) is one of the most serious complications of neuroleptic treatment and the optimal therapeutic aftercare regimen for patients is unclear. Also, it is not clear if low-dose neuroleptic maintenance in such patients is safe and efficient enough over time. METHOD : We present a case of a 56-year-old woman suffering from schizoaffective disorder, who was successfully treated with a low dosage of clozapine for 6.5 years following a NMS episode. RESULT : To the best of our knowledge this is the first report of such a long-term beneficial use of low-dose clozapine in a patient who previously underwent such a serious complication. CONCLUSION : Large-scale studies are needed to substantiate this observation. (Int J Psych Clin Pract 2002; 6: 121-123)

Frequency of neuroleptic malignant syndrome in a large psychiatric hospital in Moscow

A ten-year prospective survey of neuroleptic malignant syndrome (NMS) was performed in a major psychiatric hospital (1,510 beds) in Moscow. All inpatients who developed a persistent and severe extrapyramidal rigidity accompanied by fever after exposure to neuroleptic medication were screened for NMS. The diagnosis of NMS was established according to Levenson’s criteria and at a later stage all NMS cases were reevaluated using the DSM-IV research criteria. Data on age, gender and psychiatric diagnoses were analyzed. Of the 78,708 inpatients treated with neuroleptic agents, 19 separate patients had an episode of NMS, for a frequency of 0.02%. Mortality rate was 10.5% (2/19 patients). Of the three potential risk factors studied, only young age (≤ 25 years) was significantly associated with an increased frequency of NMS ( P < 0.01). The low rate of NMS found here compared to studies in other countries may be due to the stringent demands for NMS diagnosis. More large-scale prospective studies including detailed clinical and laboratory data are needed to clarify these differences and their impact on the prevalence and risk factors of NMS.

Risperidone, neuroleptic malignant syndrome and probable dementia with Lewy bodies

1. 1 . Conflicting reports are available regarding the sensitivity of patients with Dementia with Lewy bodies (DLB) to risperidone. 2. 2. The authors studied a rare familial case of probable DLB, who developed a documented episode of neuroleptic malignant syndrome (NMS) following the exposure to risperidone. Previously, the patient had had an episode of NMS on trifluoperazine. 3. 3. The discontinuance of risperidone, in combination with a mild increase of dopaminergic therapy, led to a complete recovery in few days. 4. 4. In patients with DLB, a continued vigilance for extrapyramidal side effects, including NMS, would be advisable during the use of risperidone.

Dr. Gurrera Replies

Back to table of contents Previous article Letter to the EditorFull AccessDr. Gurrera RepliesRONALD J. GURRERA, M.D., RONALD J. GURRERASearch for more papers by this author, M.D., Brockton, Mass.Published Online:1 Apr 2000AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The issues raised by Drs. Duggal and Nizamie are too numerous and diffuse to address within the limitations of a letter, so I will direct my remarks to the principal focal point of their commentary, which concerns the role of dopamine antagonism in the pathophysiology of neuroleptic malignant syndrome.First, Drs. Duggal and Nizamie are unimpressed by the data linking hypothermia to dopamine antagonism and wonder (if only rhetorically) why hypothermia is not observed more frequently in neuroleptic malignant syndrome. A good deal of controversy in the literature of neuroleptic malignant syndrome centers on which clinical features ought to be considered essential for diagnosis; hyperthermia—the most dramatic and prognostically important sign—is usually accorded this status. This prevailing view has almost certainly reduced the likelihood that any episode resembling neuroleptic malignant syndrome that involves normal or subnormal body temperatures will be recognized or reported. Without intending to, Drs. Duggal and Nizamie have asked an incisive question, which I attempted to answer by reexamining our original database (1).Of the 65 suspected episodes of neuroleptic malignant syndrome involving 45 patients, 22 episodes (33.8%)—involving 20 patients (44.4%)—had at least one subnormal body temperature nadir recorded within 7 days of the date that the episode reached maximal intensity. Nadirs (lowest temperatures recorded on any given day) ranged from 93.3°F to 98.2°F. Diaphoresis was observed in 11 (50%) of the episodes and more frequently in episodes with the lowest temperature nadirs, although this difference was not statistically significant (median split: 63.6% and 36.4%, respectively; Pearson’s χ2=1.64, df=1, p=0.20). Episodes with observed diaphoresis had a lower mean temperature nadir than episodes without observed diaphoresis, but once again this difference failed to reach statistical significance (95.8°F, SD=0.81; 96.7˚F, SD=1.44, respectively) (p=0.13, n.s.). These data should be treated cautiously because temperatures were taken orally, so patients’ inability to cooperate would tend to bias measurements toward lower temperatures. However, these data suggest that hypothermia may be more common in neuroleptic malignant syndrome than has been appreciated and that excessive diaphoresis may play a role. As Drs. Duggal and Nizamie imply, oscillations between hypo- and hyperthermia in neuroleptic malignant syndrome would be consistent with the model that I have proposed.Second, they disapprove of the emphasis given in that model to dopaminergic modulation of sympathetic activity at the level of the spinal cord, but in support of their view they offer only a dogmatic assertion that the “antipsychotic effect of neuroleptics is due to dopamine antagonism at the level of brain and not at the level of spinal cord.” I am unaware of any data that would validate this arbitrary distinction, and it seems premature to exclude involvement of the lower central and/or peripheral nervous system from the phenomenology of psychotic disorders.In any event, Drs. Duggal and Nizamie have misconstrued one of the main points of my article, which is that whatever contribution is made by antagonism of the hypothalamic dopamine receptors to the pathophysiology of neuroleptic malignant syndrome, it is insufficient in itself to account for most of the observed clinical phenomena.

NMS and HIV

Back to table of contents Previous article Next article LetterFull AccessNMS and HIVEwald Horwath, M.D., and Francine Cournos, M.D.Ewald HorwathSearch for more papers by this author, M.D., and Francine CournosSearch for more papers by this author, M.D.Published Online:1 Apr 1999https://doi.org/10.1176/ps.50.4.564AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: In their excellent review of neuroleptic malignant syndrome (NMS) published in the September 1998 issue, Pelonero and associates (1) called attention to the role of poorly controlled or treatment-resistant extrapyramidal symptoms as risk factors for NMS. We would like to amplify this point and call attention to the association between HIV infection and increased sensitivity to extrapyramidal symptoms. Several authors have reported on cases of NMS in patients with AIDS, leading us to wonder whether advanced HIV infection may be a risk factor for NMS.Breitbart and associates (2) reported three cases of NMS in patients with AIDS dementia who were treated with neuroleptics. Rosebush and Stewart (3) reported on 24 cases of NMS occurring in 20 patients, one of whom was a 31-year-old man with AIDS. Swenson and associates (4) reported a case of AIDS and dementia in a man who developed severe extrapyramidal symptoms with many features of NMS while being treated with a phenothiazine, prochlorperazine, as an antiemetic. Vogel-Scibilia and colleagues (5) identified an episode of NMS in a literature review of 13 cases of HIV infection presenting as psychosis, of whom seven were treated with neuroleptics.These case reports call attention to the possible role of HIV infection as a risk factor for NMS. Several of these authors observe that HIV infection of the central nervous system may increase a patient's susceptibility to extrapyramidal symptoms. If increased sensitivity to extrapyramidal symptoms is a risk factor for NMS, as Pelonero and associates suggest, then it follows that HIV infection may predispose to NMS.Of note, five of the six cases of NMS reported by the authors cited above occurred in patients with AIDS, and most involved the use of standard, as opposed to atypical, antipsychotics. Some authors have suggested that the increased sensitivity to extrapyramidal symptoms may be a direct effect of HIV on the basal ganglia. At the very least, clinical caution is indicated when using standard antipsychotics in the treatment of patients with advanced HIV infection or AIDS.Dr. Horwath is associate clinical professor of psychiatry and Dr. Cournos is professor of clinical psychiatry at Columbia University College of Physicians and Surgeons in New York City.

Mutation involving cytochrome P450IID6 in two Japanese patients with neuroleptic malignant syndrome

Cytochrome P450IID6 (CYP2D6) plays an important role in the hepatic metabolism of various psychotropic drugs. We detected a mutation of the CYP2D6 gene in two patients who previously had episodes of neuroleptic malignant syndrome (NMS). They were homozygous for a mutated CYP2D6J allele conferring a poor-metabolizer phenotype. Possession of this trait may contribute to susceptibility to NMS.

Neuroleptic malignant syndrome. Recognition, prevention and management.

Neuroleptic malignant syndrome (NMS) is a rare but potentially lethal form of drug-induced hyperthermia characterised by mental status changes, muscle rigidity, hyperthermia and autonomic dysfunction. Increased awareness and early recognition will lead to prompt management. The diagnosis of NMS presents a challenge because several medical conditions generate similar symptoms. The presentation and course of NMS can be quite variable ranging from a stormy and potentially fatal course to a relatively benign and self-limiting course. The most important aspect of treatment is prevention. This includes reducing risk factors (e.g. dehydration, agitation and exhaustion), early recognition of suspected cases and prompt discontinuation of the offending agent. All patients with psychosis should be monitored daily for dehydration and elevated temperature, have vital signs checked and agitation should be watched for. Antipsychotics should be used conservatively with gradual titration of doses. The management of NMS should be based on a hierarchy of symptom severity. Following an episode of NMS, the patient should be reassessed for further treatment with antipsychotics and rechallenge should not be attempted at least 2 weeks following resolution of symptoms of NMS. The patient and family should be educated about the episode and consent for further medication use obtained after a clear explanation of the risk-benefit analysis.

Neuroleptic malignant syndrome in parkinsonian patients: risk factors.

A syndrome resembling the neuroleptic malignant syndrome (NMS) is known to develop occasionally following interruption of dopaminergic medications in patients with Parkinson's disease. However, NMS can develop even without withdrawal of antiparkinsonian drugs. In parkinsonian patients who continually received dopaminergic medications, the development of NMS occurred exclusively in warm seasons, May to August. The development of NMS could occur at any season in association with the cessation of dopaminergic drugs. A female parkinsonian patient showed two episodes of NMS during the premenstrual period. It is suggested that hot weather or dehydration and aggravation of parkinsonism premenstrually constitute risk factors for the development of NMS, in addition to withdrawal of antiparkinsonian drugs.