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.     

Serum iron in catatonia and neuroleptic malignant syndrome

AIMS: The purpose of this study was to investigate, within the context of the Danish Breast Cancer Cooperative Group (DBCG) programmes, whether a dedicated surgical approach had a significant bearing on the outcome of breast cancer treatment. METHODS: From 1 January 1980 to 31 December 1990, patients below 70 years of age with operable breast cancer from Odense University Hospital (n=743) were compared with those from the rest of Denmark (denoted rest-DK) (n=15,419). All patients were treated according to nationwide DBCG guidelines and reported to the DBCG Data Centre. The potential median observation time was 11.2 years (range 6.0-16.9). Patients underwent mastectomy or breast conserving therapy, and high risk lymph-node positive patients had adjuvant systemic therapy with or without radiotherapy. RESULTS: Comparing total patients series, overall survival (OS) was significantly superior in patients from Odense compared with rest-DK (P=0.02), with 10-year OSs of 62% (95% CI: 58-65%) and 56% (55-57%), respectively. In subgroups, the OS of low-risk node negative patients (protocol A) in Odense compared with rest-DK was significantly better (P=0.02); 10-year OS was 78% (73-84%) versus 72% (70-73%). Among the high-risk pre-menopausal patients (protocol B), the OS was significantly better in Odense (P=0.009); 10-year OS was 67% (60-75%) versus 53% (51-55%) in rest-DK. Post-menopausal high-risk patients (protocol C) did not differ significantly in OS between Odense and rest-DK (P=0.61). Locoregional control in the Odense series was superior compared with rest-DK. More lymph nodes were recovered and examined from the axilla in the Odense series than in rest-DK, a median of 10 vs. 6 nodes. In the Odense series, a significantly higher proportion of pre-menopausal patients had positive lymph nodes, predominantly one to three positive nodes, and subsequently a lower proportion of pre-menopausal patients had negative lymph nodes compared with rest-DK (P=0.02), indicating a more accurate staging in Odense vs. rest-DK. The survival benefit among the patients from Odense cannot be explained by stage migration alone, but seems to represent a true survival advantage. Overall mortality was significantly lower in the Odense series compared with rest-DK. Whether or not this difference could be explained by lower background mortality in the Odense series or was caused by superior treatment is discussed. CONCLUSIONS: The extent of surgery seems important for locoregional tumour control and accurate axillary lymph-node staging. In combination, these might lead to superior recurrence-free and overall survival, although differences in background mortality cannot be ignored. Surgery, therefore, might represent a risk factor by itself.     

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.     

CYP2D6 HhaI genotype and the neuroleptic malignant syndrome

This prospective, double-blinded evaluation of 24 osteoarthritic patients undergoing bilateral total knee replacement compared the midvastus and standard parapatellar approaches. The midvastus approach was found to offer an early advantage in terms of less pain and earlier return to function. There were no significant complications associated with the midvastus approach. This approach should be a part of the knee surgeon's armamentarium.     

Malignant hyperthermia and neuroleptic malignant syndrome in a patient during treatment for acute asthma

PURPOSE: The safety and diagnostic efficacy of iodixanol (Visipaque) 270 mg I/ml was compared to that of iopamidol (Iopamiron) 300 mg I/ml in knee arthrography. MATERIAL AND METHODS: This trial was a bi-center double-blind trial including 128 patients (iodixanol/iopamidol 64/64 patients). Efficacy was evaluated by blinded grading of the diagnostic quality of the p.a. images taken 0, 12 and 25 min after contrast administration by the examining radiologist and later at a consensus evaluation by two experienced skeletal radiologists. Adverse events were recorded. RESULTS: No patient experienced any adverse event. The proportion of better images at both 12 and 25 min after injection was higher in the iodixanol group compared to the iopamidol group both by the examining radiologist and at the consensus evaluation. CONCLUSION: In the knee joint iodixanol is a safe contrast medium. The contrast effect of iodixanol lasted longer than that of iopamidol, which can be important when performing arthrography, especially CT arthrography, where the time between puncture and examination can be prolonged.     

A study of neuroleptic malignant syndrome in the presenium and senium]

The role of the mammalian phospholipase D (PLD) in the control of key cellular responses has been recognised for a long time, but only recently have there been the reagents to properly study this very important enzyme in the signalling pathways, linking cell agonists with intracellular targets. With the recent cloning of PLD isoenzymes, their association with low-molecular-weight G proteins, protein kinase C and tyrosine kinases, the availability of antibodies and an understanding of the role of PLD product, phosphatidic acid (PA), in cell physiology, the field is gaining momentum. In this review, we will explore the molecular properties of mammalian PLD and its gene(s), the complexity of this enzyme regulation and the myriad physiological roles for PLD and PA and related metabolic products, with particular emphasis on a role in the activation of NADPH oxidase, or respiratory burst, leading to the generation of oxygen radicals.     

Rhabdomyolysis and acute renal failure caused by haloperidol-decanoate (neuroleptic malignant syndrome)

A case of rhabomyolysis with attendant severe acute renal failure, arisen in a 59-year-old male treated with haloperidol-decanoate, is presented. The patient has been affected by paranoia schizophrenia since childhood, and he was treated with electroshock and successively with neuroleptics p.o. Four years before our observation, a therapy with haloperidol decanoate (50 mg i.m. monthly) was started. After some time, catatonic like episodes appeared, which got more and more frequent, until they appeared weekly. In occasion of the last of them, he was admitted to our hospital. At the objective examination he presented psychomotory arrest, perspiration, mytacism, severe muscle rigidity, moderate oedems to lower limbs. Laboratory findings showed a pattern consistent with rabdomyolysis and severe renal failure. After that haloperidol decanoate was stopped and rehydration and intensive diuretic therapy was started, the clinical and laboratory pattern went normal, persisting however a light creatinine increase. Probably the rhabdomyolysis was induced by the haloperidol decanoate, and renal failure by secondary severe hyvolemia. This case comes into the so-called neuroleptic malignant syndrome which can rarely arise in patients treated with antipsycotic agents and which causes high mortality, particularly when there are rhabdomyolysis and acute renal failure.     

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.     

Risk factors for reduced pulmonary function after malignant lymphoma in childhood

The aim was to study pulmonary function after Hodgkin disease or non-Hodgkin Lymphoma in childhood and to evaluate if younger age at diagnosis and therapy is a risk factor for reduced pulmonary function. We studied a population-based sample of survivors of Hodgkin disease (n = 22) or non-Hodgkin lymphoma (n = 19) in childhood. Pulmonary function test results were compared with reference values for our laboratory, generated by adjusting published reference values fit 348 healthy never-smokers from a local population study. Data were analyses as standardised residuals, which are [observed minus predicted value] divided by the residual standard deviation of the reference equations. At a median of 11 years after diagnosis (range 2 to 24), the participants had significantly reduced lung volumes and transfer factor, unrelated to the few pulmonary symptoms. On average, the total lung capacity was reduced to -0.9 standardised residual and the transfer factor was reduced to -1.3 standardised residual. Young age at therapy seemed to be a risk factor for reduced lung function, especially when treatment included thoracic irradiation. No significant toxic synergism was observed between smoking and previous cancer therapy. Therapy without thoracic irradiation but with doxorubicin and cyclophosphamide was almost as toxic to lung function as therapy with thoracic irradiation but without doxorubicin and cyclophosphamide. In conclusion, lung volumes and transfer factor were reduced several years after childhood Hodgkin disease of non-Hodgkin lymphoma, with young age at therapy as a risk factor, especially when combined with thoracic irradiation.     

Risk factors in dengue shock syndrome

Despite a growing body of evidence predominantly, but not exclusively, from Thailand suggesting that the risk of developing dengue shock syndrome (DSS) is greatest following an anamnestic dengue infection, particularly if the most recent infection was with dengue 2 virus, there continues to be debate about the justification for these claims. This report describes a five-year, prospective study in two townships (suburbs) in Yangon (Rangoon) Myanmar (Burma) in which attempts were made to confirm the data from an earlier prospective study in Thailand and to address some of the criticism of earlier studies. This investigation found the incidence of anamnestic dengue infections in DSS patients to be significantly higher than in the community from which they were drawn and a significantly higher risk of developing DSS following an anamnestic infection (particularly with dengue 2 virus) than following a primary infection with any serotype.     

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.     

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

Traumatic injuries of arteries lead to acute bleeding or ischemia. In the hand, which is perfused by two arteries, this symptom could be missed. The hypothenar hammer syndrome is a traumatic occlusion of the distal arteria ulnaris. Dependent on the mechanism of the trauma the clinical symptoms may appear late. A specific angiographic or duplex sonographic diagnostic investigation is necessary to show the arterial occlusion. There is no proven therapeutic procedure. Exact diagnosis of the occlusion as an effect of the trauma is important for the patient and is the basis of any therapeutic intervention.     

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.