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.     

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.     

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.     

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.     

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.     

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.     

Late complication of laparoscopic salpingoophorectomy: retained foreign body presenting as an acute abdomen

The technique of immunocytochemistry was used to identify myoglobin in kidney, confirming a diagnosis of neuroleptic malignant syndrome following an otherwise obscure autopsy in a decomposed body. The features of neuroleptic malignant syndrome are reviewed with a differential diagnosis of myoglobin renal casts. The report emphasizes a thorough and detailed assessment of deaths which occur during treatment with neuroleptic drugs.     

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.     

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.     

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.     

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.     

Hypothesis explaining simultaneous development of acquired immunodeficiency syndrome and malignant tumors

A possible mechanism for explanation of the simultaneous development of acquired immunodeficiency syndrome (AIDS) and malignant tumors may be based on the cell-fusion process with the participation of immunocompetent cells. If the fusion proceeds with a high intensity, i.e. a great number of cells (including immunocompetent cells) are involved in the process, it will cause a rise in multinuclear formations-polykaryocytes. Since polykaryocytes are incapable of proliferation, their formation is equivalent to elimination of immunocompetent cells and may lead to immunodeficiency. If the intensity of fusion is low, the occurrence of binuclear formations- dikaryons-seems more frequent. We have shown (1) a possibility of the transformation of dikaryons into tumor cells under certain conditions and since immunocompetent cells are dominant by their phenotypic properties the malignant cells in AIDS should have mainly macrophage, lymphoid or intermediate morphology. Even low doses of various chemical carcinogens may cause malignancy by the formation of special defects in plasma membrane which promote cell fusion, whereas under high doses of carcinogens (or high intensity of their action) the formation of polykaryocytes and the development of immunodeficiency seem more probable, though it does not exclude the possibility of cancer development.     

Bone marrow transplantation in primary immunodeficiency syndrome and in osteopetrosis

The designation primary immunodeficiency embraces a multiplicity of diseases of which only the more severe constitute indications for BMT (bone marrow transplantation)--e.g. severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, familial haemophagocytic lymphohistiocytosis and malignant osteopetrosis. In cases of immunodeficiency, the outcome of BMT is strongly dependent on the patient's age, clinical status at transplantation and the type of immunodeficiency. In children with SCID who undergo BMT during the first few months of life, lasting cures can be obtained in almost 100 percent of the cases, whereas there is only a 15 percent probability of success if the child is older, infected, cannot undergo cytostatic preconditioning or cannot be given T-cell depleted bone marrow.     

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.     

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 associated with olanzapine

OBJECTIVE: To report a case of neuroleptic malignant syndrome (NMS) associated with the use of olanzapine. CASE SUMMARY: A 67-year-old white man with bipolar disorder developed nausea and vomiting. After 12 days, he became confused, delirious, and manic. His only medications were olanzapine 10 mg/d and divalproex sodium 500 mg bid. He was admitted to a hospital and treated for dehydration and mania. Olanzapine was given on 6 of the first 7 hospital days. On hospital day 6, typical NMS developed with the body temperature increasing to 39.9 degrees C, obtundation, rigidity, tremor, diaphoresis, fluctuating pupillary diameter, labile tachycardia and hypertension, hypernatremia, and elevated serum creatine kinase. Olanzapine was stopped after hospital day 7, and the syndrome resolved by hospital day 12. DISCUSSION: The patient had all of the major manifestations of NMS. There was no other likely explanation for his illness and he received no other drug likely to be associated with the syndrome. This is the first case reported in which NMS was associated with olanzapine.     

Sj?gren's syndrome

Sj?gren's syndrome is a multisystemic connective tissue disease. The syndrome is associated with other major connective tissue disorders, such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and others, Reticulo-endothelial malignances have repeatedly been reported in patients with Sj?gren's syndrome. A clinical study of 20 patients with Sj?gren's syndrome was performed in the Department of otolaryngology, Rikshospitalet, Oslo, Norway. A considerable complexity of symptoms was seen. One patient with malignant lymphoma and one with a thyroid carcinoma were encountered.     

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.     

Treatment of infections in the patient with acquired immunodeficiency syndrome

Modern technology has led to a contemporary medical practice that must be able to manage a variety of opportunistic infections in the immunocompromised host. The most common causes of immune suppression are immunosuppressive therapy after organ transplantation, granulocytopenia secondary to cancer chemotherapy, and the human immunodeficiency virus (HIV). All of these forms of immunosuppression predispose patients to a wide variety of opportunistic infections caused by reduction in T- and B-cell lymphocyte function as well as depression of neutrophils. However, the acquired immunodeficiency syndrome (AIDS) has presented the clinician with the greatest challenge in this area. Therefore, it is imperative that physicians and other health care professionals have a comprehensive understanding of the recommended therapy as well as the epidemiology, pathogenesis, and diagnosis of the various infections in these patients.     

Pulmonary cryptosporidiosis in patients with acquired immunodeficiency syndrome

Several reports have showed Cryptosporidium species as a cause of intractable diarrhea and malabsorption in patients with acquired immunodeficiency syndrome (HIV). A case of chronic diarrhea in a drug addict woman associated with a symptomatic interstitial pulmonary infection due to Cryptosporidium parvum is described. This unusual C. parvum spread into the bronchial tree is underlined and a survey of the literature is made.