Lack of association between neuroleptic malignant syndrome and polymorphisms in the 5-HT1A and 5-HT2A receptor genes

OBJECTIVE: The molecular basis of neuroleptic malignant syndrome is unclear, but studies suggest that genetic factors are involved in its pathogenesis. Considering possible involvement of the serotonergic system in neuroleptic malignant syndrome, the authors examined the association between neuroleptic malignant syndrome and polymorphisms of the 5-HT1A and 5-HT2A receptor genes. METHOD: The authors examined the frequencies of gene polymorphisms in the 5-HT1A (Arg219Leu) and 5-HT2A (Thr25Asn and His452Tyr) receptor genes in 29 patients previously diagnosed with neuroleptic malignant syndrome, 94 neuroleptic-treated patients with schizophrenia who had no history of neuroleptic malignant syndrome, and 94 healthy comparison subjects. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to screen gene mutations. RESULTS: No polymorphic allele was detected in the patients who had experienced the neuroleptic malignant syndrome. CONCLUSIONS: The authors cannot conclude that polymorphisms in the 5-HT1A and 5HT2A receptor genes are factors determining susceptibility to the neuroleptic malignant syndrome.     

Myoglobinuria, malignant hyperthermia, neuroleptic malignant syndrome and serotonin syndrome

This article presents an overview of the causes and manifestations of myoglobinuria and provides criteria for its diagnosis and management. The article also reviews neuroleptic malignant syndrome, malignant hyperthermia, and serotonin syndrome, all of which could cause rhabdomyolysis and myoglobinuria.     

Catatonia, malignant neuroleptic syndrome and myositis ossificans

Lethal catatonia and the malignant neuroleptic syndrome represent two potentially fatal disorders that require different therapeutic regimens. Clinical differentiation is considered difficult because of a number of similarities with respect to mode of onset, signs and symptoms, and outcome. Recent observations emphasizing similarities between the two disorders, however, suggest that catatonia and the malignant neuroleptic syndrome may not represent separate diagnostic entities. Instead, the malignant neuroleptic syndrome has been hypothesized to be a neuroleptic-aggravated form of catatonia. In the present paper, we report the case of a 22-year-old male who developed different forms of malignant neuroleptic syndromes subsequent to a catatonic episode and overlapping it. In addition, the course was complicated by the occurrence of heterotopic calcification within skeletal muscles. The clinical value of diagnostic criteria that help distinguish catatonia from neuroleptic malignant syndrome and their therapeutic consequences are discussed.     

Parental decisions to use infant walkers

A 1-year-old female presented with neuroleptic malignant syndrome probably caused by methylphenidate. She had defects in the supratentorial brain including the basal ganglia and the striatum (multicystic encephalomalacia) due to severe perinatal hypoxic-ischemic encephalopathy, which was considered to be a possible predisposing factor causing neuroleptic malignant syndrome. A dopaminergic blockade mechanism generally is accepted as the pathogenesis of this syndrome. However, methylphenidate is a dopamine agonist via the inhibition of uptake of dopamine, and therefore dopaminergic systems in the brainstem (mainly the midbrain) and the spinal cord were unlikely to participate in the onset of this syndrome. A relative gamma-aminobutyric acid-ergic deficiency might occur because diazepam, a gamma-aminobutyric acid-mimetic agent, was strikingly effective. This is the first reported patient with neuroleptic malignant syndrome probably caused by methylphenidate.     

Behr''s syndrome. A report of 2 siblings studied by MR

Neuroleptic malignant syndrome is an idiosyncratic reaction associated with the use of neuroleptic drugs. We report a case of this rare syndrome in a head injury patient associated with some unusual features: rhabdomyolysis with a high level of creatine kinase, the development of acute renal failure, the early use of continuous venovenous haemofiltration in treatment and rigidity that was refractory to conventional treatment with dantrolene and bromocriptine. The diagnosis in patients with multiple injuries must be based on a high index of suspicion.     

The neuroleptic malignant syndrome: a logical approach to the patient with temperature and rigidity

The neuroleptic malignant syndrome is a rare, potentially fatal, adverse reaction to neuroleptic drugs characterised by severe rigidity, high temperature and autonomic dysfunction. In the light of the hypothesized pathophysiology of this condition, a rational approach to the management of patients presenting with temperature and rigidity is provided. The aims of this approach are three-fold: to reduce the incidence of the condition, to be able to recognise it early so as to treat before life-threatening complications arise, and to be able to recognise early those conditions which mimic neuroleptic malignant syndrome, so as not to delay their specific treatment.     

Neuroleptic malignant syndrome in the acquired immunodeficiency syndrome

Patients infected by the human immunodeficiency virus are predisposed to many infectious and noninfectious complications and often receive a variety of drugs. Furthermore, they seem to have a particular susceptibility to idiosyncratic adverse drug reactions. It is therefore surprising that only a few cases of the neuroleptic malignant syndrome have been described in patients with the acquired immunodeficiency syndrome. A high index of suspicion is required to diagnose the neuroleptic malignant syndrome in these patients, as its usual manifestations, including fever and altered consciousness, are frequently attributed to an underlying infection.     

Cardiac arrhythmia associated with malignant neuroleptic syndrome: description of 2 clinical cases

Malignant neuroleptic syndrome (alteration of consciousness, muscle rigidity and hyperthermia) is a potentially lethal condition, due also to its life-threatening complications. In particular, hypokinetic and hyperkinetic arrhythmias can be rare and severe early manifestations of this illness, and they deserve a careful approach because of their drug-refractoriness. Arrhythmias associated with the malignant neuroleptic syndrome depend on various mechanisms: neurotransmitter receptor blockades typical of neuroleptic drugs, clustered lipid droplets among the cardiac myofibrils and possible electrolytic disorder due to diaphoresis. The two cases described here presented hypokinetic and hyperkinetic (supraventricular and ventricular) arrhythmias. The arrhythmias, which failed to respond to antiarrhythmic drugs, were temporarily suppressed by DC shock, over-drive pacing and correction of electrolytic imbalance. In case 1, prolonged bromocriptine treatment was required. Complete wash-out of the causative agents resulted in lasting regression of arrhythmias. In conclusion, a correct treatment and a favourable outcome of this syndrome can be achieved only through early diagnosis.     

Nephrology update--III. Renal artery stenosis--rational diagnosis

Neuroleptic malignant syndrome is a rare, idiosyncratic condition related to neuroleptic use which may develop at any stage during neuroleptic treatment and can prove fatal. Although most commonly seen in psychiatric patients, anyone prescribed a neuroleptic is at risk and it has been associated with other agents. This article discusses its recognition, risk factors, clinical course and treatment, together with a summary of current thinking on its aetiology.     

Neuroleptic malignant syndrome in the elderly: description of 4 patients

The neuroleptic malignant syndrome is a fulminant, life-threatening reaction to neuroleptic medication. It is characterized by fever, rigidity, autonomic disfunction and fluctuating consciousness. Usually described in young adults with psychiatry illnesses, its presentation in an elderly population has received scant attention in medical literature. We describe the clinics and evolutive characteristics of 4 cases of this syndrome in elderly which a mean age of 78 years. We emphasise about the existence of a brain organic illness with dementia as a predisposing factor, and the correct evolution of the showed cases in probably relation with measures and drug therapy.     

The National Workshop to Develop the Chiropractic Research Agenda

Emigration is often followed by psychic disorders. The special issue of Germans from the GUS-States immigrating to Germany is presented. The modus of paranoid reaction is discussed along the biography and the criteria of ICD 10. The acute paranoid psychosis was complicated by a neuroleptic malignant syndrome.     

Serum procalcitonin rise is only slight in two cases of disseminated aspergillosis

A 19-year-old man presented to a community hospital with a sudden change in level of consciousness, fever, and muscle rigidity. The patient had a history of schizophrenia and was being treated with clozapine. Despite a high index of suspicion for neuroleptic malignant syndrome, definitive care was delayed for more than 24 hours after the patient was transferred to a tertiary care center. This case illustrates the importance of primary care physicians being able to recognize and diagnose this syndrome, particularly as the use of atypical antipsychotic agents increases.     

Salazopyrine and male fertility

We report on a young patient with a positive family history for malignant hyperthermia (MH), who was diagnosed as susceptible to MH in our malignant hyperthermia laboratory by the in vitro-contracture test. Prior to the investigation of MH-susceptibility, the patient had been on medication with moclobemide, a monoamine oxidase (MAO) inhibitor, over a period of 13 months for treatment of a hyperactivity disorder. During the therapy with moclobemide no signs of relevant side effects were observed. However, some authors regard MAO-inhibitors as MH-triggering agents. The risk of MH-patients due to the therapy with MAO-inhibitors and the association between MH and the neuroleptic malignant syndrome is discussed in this case report.     

Clinical impact of cerebral dopamine-D2 receptor scintigraphy

The present review describes findings and clinical indications for the dopamine D2 receptor scintigraphy. Methods for the examination of D2 receptors are positron emission tomography (PET) using 11C- or 18F-labelled butyrophenones or benzamides or single photon emission tomography (SPECT) using 123l-iodobenzamide (IBZM) respectively. The most important indication in neurology is the differential diagnosis of Parkinsonism: patients with early Parkinson's disease show an increased D2 receptor binding (D2-RB) compared to control subjects. However, patients suffering from Steele-Richardson-Olszewski-Syndrome or Multiple System Atrophy show a decreased D2-RB and are generally non-responsive to treatment. Postsynaptic blockade of D2 receptors results in a drug induced Parkinsonian syndrome, which can be diagnosed by D2 scintigraphy. Further possible indications occur in psychiatry: the assessment of receptor occupancy is useful in schizophrenic patients treated with neuroleptics. Additionally, D2 receptor scintigraphy might help to clarify the differential diagnosis between neuroleptic malignant syndrome and lethal catatonia. The method might be useful for supervising neurobiochemical changes in drug dependency and during withdrawal. Assessment of dopamine D2 receptor binding can simplify the choice of therapy in depressive disorder: patients showing a low D2 binding are likely to improve following an antidepressive drug treatment whereas sleep deprivation is promising in patients with high D2 binding.     

Hemostatic evaluation of a patient with haloperidol-induced neuroleptic malignant syndrome associated with disseminated intravascular coagulation

A 94-year-old man who had been admitted to our hospital for the treatment of senile dementia and restless behavior exhibited consciousness disturbances, acute respiratory failure, high fever, and thrombocytopenia the day after receiving haloperidol as prescribed by a psychiatrist. On the fourth day following administration of haloperidol, acute renal failure with rhabdomyolysis and disseminated intravascular coagulation (DIC) developed in the patient, who was accordingly given a diagnosis of haloperidol-induced neuroleptic malignant syndrome (NMS) associated with DIC. He was then given heparin and antithrombin III, and his DIC symptoms improved soon thereafter. Elevated plasma levels of tissue factor and tumor necrosis factor-alpha (TNF-alpha) were sustained during this therapy course. Other cytokines, including interleukin IL-1 beta, IL-2 and IL-6, were not elevated. There are activation of extrinsic coagulation and an elevated level of TNF-alpha during acute renal failure and rhabdomyolysis associated with NMS, which is thought to trigger the onset of DIC.     

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperiodol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35 degrees C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

Neuroleptic malignant syndrome and clozapine monotherapy

OBJECTIVE: This report identifies neuroleptic malignant syndrome (NMS) occurring on a steady state dosage of clozapine monotherapy. CLINICAL PICTURE: An outpatient presented with a recent history of stiffness and soreness of his legs, dizziness, polydipsia, polyuria, abdominal and chest pains. After admission to a general hospital, further symptomatology was identified including: pallor, diaphoresis, nausea, confusion, agitation, decrease in normal reflexes, minimally reactive pupils and rigid limbs. TREATMENT: Intravenous (I/V) diazepam was administered but failed to decrease the agitation and confusion. He was sedated with the administered of I/V droperadol, intubated and placed on a ventilator with circulatory supports for 4 days. OUTCOME: On day five he was extubated and transfered to a medical ward. All laboratory values had returned to normal values by this time. The patient was subsequently discharged. CONCLUSIONS: Neuroleptic malignant syndrome can occur at any stage of clozapine treatment, and the patient can be rechallenged after such an episode. This person was rechallenged and after 6 months of treatment has suffered no further recurrence of NMS.     

Acute hyponatremia and neuroleptic malignant syndrome in Parkinson's disease

1. The neuroleptic malignant syndrome (NMS) may occur, occasionally, in Parkinson's disease (PD) after withdrawal of antiparkinsonian drugs. However, the circumstances in which the NMS occurs and the pathophysiologic mechanisms remain uncertain. 2. The authors studied a woman with PD, who developed hyperthermia, increased muscular tone, tremor, signs of autonomic dysfunction and stupor as symptoms of acute hyponatremia due to gastrointestinal loss of sodium in excess of water. 3. The correction of hyponatremia led to a complete recovery after about 6 hours. During this period the antiparkinsonian therapy was not modified. 4. An acute imbalance of sodium in the central nervous system may play a role in the pathophysiology of NMS.     

A case of Satoyoshi syndrome with symptoms resembling neuroleptic malignant syndrome]

Satoyoshi syndrome is a rare neurological disorder of unknown etiology characterized by progressive muscle spasms, alopecia, diarrhea and skeletal abnormalities. We here describe a 25-year-old man who developed symptoms similar to neuroleptic malignant syndrome (NMS). He began to have the clinical characteristics of Satoyoshi syndrome at the age of 12 years. He was admitted to hospitals many times with painful muscle spasms and pyrexia in the early stage of the disease. He received steroid pulse therapy and oral prednisone at the age of 19, the extent and frequency of the spells being reduced thereafter. He was admitted to our hospital due to recurrence of his usual muscle spasms. He was treated with midazolam intravenously to relieve severe muscle ache, pain in the left shoulder, and insomnia. About 90 minutes later, he became comatose, with the following manifestations: hyperthermia, low blood pressure, tachycardia, profuse perspiration, acute respiratory failure, and ensuing cardiac arrest. He developed rhabdomyolysis, acute renal failure, hepatic damage, and diffuse intravascular coagulation. Serum creatine kinase level was elevated to 306,910 IU. He died of multiple organ failure 13 days after admission. His symptoms resembled NMS and malignant hyperthermia (MH). None of patients with Satoyoshi syndrome accompanied by NMS or MH have been reported. It remains to be clarified whether midazolam administration induces NMS in Satoyoshi syndrome. Nevertheless, careful attention should be paid when one administers midazolam to patients with this syndrome.     

Severe digoxin intoxication in a 15-year-old girl treated with Fab antidigoxin

The precise aetiology of sudden death in patients receiving neuroleptic medication is uncertain, but cardiac arrhythmias are a possible cause. We investigated the link between neuroleptic medication and electrocardiographic changes predictive of malignant cardiac arrhythmias. Electrocardiographs were performed on 111 patients receiving neuroleptic medication and on 42 unmedicated controls. Prolonged QTc intervals were more common in the patient sample, but QTc dispersion was not significantly increased. QTc interval prolongation was more likely in patients on doses above 2000 mg chlorpromazine equivalents daily (odds ratio 4.28, P < 0.02). Neuroleptic medication, especially at high doses, is associated with ECG changes that may herald more serious cardiac problems.