Letter: Low CK, High Suspicion: A Case of Atypical Neuroleptic Malignant Syndrome in a Pediatric Post-Transplant Patient.

INTRODUCTION The job of the pharmacist rarely involves evaluating diagnostic impressions or making definitive diagnoses. However, the pharmacist may often be called upon to give his or her assessment of a clinical picture when drugrelated or drug-induced factors may be at play. In addition, pharmacists may be called upon to give therapy recommendations, frequently evaluating appropriate dosing, drug interactions and even therapeutic endpoints of medications. As patient and drug-regimen complexity increase, the ability of the pharmacist to give valuable input to the diagnostic impression or assessment of drugrelated factors regarding a patient’s clinical presentation becomes paramount. This may be particularly true in the context of mental health patients treated with more than one psychotropic agent.

The authors' goal was to analyze reported cases of neuroleptic malignant syndrome in patients given clozapine and risperidone. They assessed 19 cases of clozapine-induced neuroleptic malignant syndrome and 13 cases of risperidone-induced neuroleptic malignant syndrome against three criteria sets and against extent of exclusionary workup and then designated them as high or low probability of being neuroleptic malignant syndrome. Nine of the 19 cases of clozapine-related neuroleptic malignant syndrome and eight of the 13 cases of risperidone-related neuroleptic malignant syndrome were designated as having high probability of being neuroleptic malignant syndrome. The remainder were designated as having low probability because presentations were not linked to treatment or failed to meet criteria for the syndrome. Neuroleptic malignant syndrome can occur in patients given atypical antipsychotics and resembles "classical" neuroleptic malignant syndrome. However, side effect profiles overlap considerably with neuroleptic malignant syndrome criteria, and atypical antipsychotics may cause neurotoxicities unrelated to (but misattributed as) neuroleptic malignant syndrome. Insufficient evidence exists for "atypical" neuroleptic malignant syndrome with novel antipsychotics.

Clozapine has been recently FDA approved and is expected to become very popular because of its efficacy and lack of extrapyramidal side effects. The neuroleptic malignant syndrome (NMS) has already been reported in two cases associated with clozapine use. In this article, we present a case in which a patient receiving clozapine monotherapy developed a complex of symptoms that appeared to be NMS without rigidity. The case meets specific criteria for NMS and the absence of rigidity may be attributable to the anatomic selectivity of clozapine's dopamine blockade.

Neuroleptic malignant syndrome (NMS) is an idiosyncratic life-threatening condition requiring prompt recognition and management. This case illustrates severe, atypical NMS with rhabdomyolysis and a creatinine-phosphokinase of 113,300 IU/L. Due to the diagnostic challenge of NMS, electro-convulsive therapy (ECT) has shown benefits in managing severe, atypical, refractory, unresponsive and undifferentiated NMS cases. Further research is needed to confirm ECT’s efficacy through randomised control trials and establish specific inclusion and exclusion criteria for ECT treatment in NMS.

The author's goal was to develop a pathophysiological model for neuroleptic malignant syndrome with greater explanatory power than the alternative hypotheses of hypothalamic dopamine antagonism (elevated set point) and direct myotoxicity (malignant hyperthermia variant). Published clinical findings on neuroleptic malignant syndrome were integrated with data from human and animal studies of muscle physiology, thermoregulation, and autonomic nervous system function. The data show that the sympathetic nervous system's latent capacity for autonomous activity is expressed when tonic inhibitory inputs from higher central nervous system centers are disrupted. These tonic inhibitory inputs are relayed to preganglionic sympathetic neurons by way of dopaminergic hypothalamospinal tracts. The sympathetic nervous system mediates hypothalamic coordination of thermoregulatory activity and is a primary regulator of muscle tone and thermogenesis, augmenting both of these when stimulated. In addition, the sympathetic nervous system modulates all of the other end-organs that function abnormally in neuroleptic malignant syndrome. There is substantial evidence to support the hypothesis that dysregulated sympathetic nervous system hyperactivity is responsible for most, if not all, features of neuroleptic malignant syndrome. A predisposition to more extreme sympathetic nervous system activation and/or dysfunction in response to emotional or psychological stress may constitute a trait vulnerability for neuroleptic malignant syndrome, which, when coupled with state variables such as acute psychic distress or dopamine receptor antagonism, produces the clinical syndrome of neuroleptic malignant syndrome. This hypothesis provides a more comprehensive explanation for existing clinical data than do the current alternatives.

Possible Paliperidone-Induced Neuroleptic Malignant Syndrome: A Case Report

Clozapine-Induced Neuroleptic Malignant Syndrome and Subdural Hematoma

Neuroleptic malignant syndrome (NMS) is a rare, but severe adverse drug reaction of drugs with anti-dopaminergic properties. The main symptoms are fever and rigor. In addition, other symptoms such as creatine kinase elevation, alteration of consciousness and various neurological symptoms may occur. A total of 52 NMS cases have been documented in the drug safety program 'Arzneimittelsicherheit in der Psychiatrie' from 1993 to 2015. We calculated incidences and analyzed imputed substances and additional risk factors to study the impact of changing therapy regimes. The overall incidence was 0.16‰. High-potency first-generation antipsychotics (FGAs) had the highest incidences, e.g. flupentixol with 0.61‰. Second-generation antipsychotics (SGAs) had lower incidences. Low-potency FGAs had very low incidences, comparable to SGAs, but in contrast to SGAs, had not been imputed alone in any case of NMS. Preexisting organic pathologies of the central nervous system, lithium treatment, infection/exsiccosis and the withdrawal of medication with anticholinergic properties or alcohol were found to be additional risk factors. With the increasing use of SGAs, one should always be aware of the risk of NMS. Better suited diagnostic criteria for 'atypical NMS' would lead to a better understanding and, therefore, to improved treatment possibilities.

This study, a retrospective chart review of 82 consecutive male inpatients, assessed the spectrum and prevalence of neuroleptic malignant syndrome. The prevalence of diagnosed neuroleptic malignant syndrome (2.4%) was greater than that generally reported. Eight additional patients manifested symptoms that abated without cessation of neuroleptic treatment. This suggests that neuroleptic malignant syndrome is a spectrum disorder that has milder variants. Affective illness may be a risk factor for its development.

Clozapine is the gold-standard antipsychotic medication for treatment-refractory schizophrenia (TRS). However, one potentially lethal side effect of clozapine, as with other antipsychotics, is neuroleptic malignant syndrome (NMS) which could present differently in clozapine therapy. 'Atypical NMS' is a recognised variant of NMS with less rigidity and delayed elevation of creatine kinase; this variant is associated with clozapine. A case from the author's clinical practice was reviewed. A 67-year-old man with TRS was treated with clozapine. Unfortunately, his physical condition deteriorated and he presented with atypical NMS, which initially was treated as presumable urinary tract infection. Atypical NMS is associated with clozapine. This case exposes the potential difficulties in diagnosis, and highlights the importance of considering less common diagnoses in acutely unwell psychiatric patients.

Emergence of Neuroleptic Malignant Syndrome While Switching Between Risperidone and Paliperidone

SummaryThe objective of this study is to report three cases of paraneoplastic or ectopic Cushing syndrome, which is a rare phenomenon of the adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome. Three cases are reported in respect of clinical presentation, diagnosis and treatment in addition to relevant literature review. The results showed that ectopic ACTH secretion can be associated with different types of neoplasm most common of which are bronchial carcinoid tumors, which are slow-growing, well-differentiated neoplasms with a favorable prognosis and small-cell lung cancer, which are poorly differentiated tumors with a poor outcome. The latter is present in two out of three cases and in the remaining one, primary tumor could not be localized, representing a small fraction of patients with paraneoplastic Cushing. Diagnosis is established in the setting of high clinical suspicion by documenting an elevated cortisol level, ACTH and doing dexamethasone suppression test. Treatment options include management of the primary tumor by surgery and chemotherapy and treating Cushing syndrome. Prognosis is poor in SCLC. We concluded that in front of a high clinical suspicion, ectopic Cushing syndrome diagnosis should be considered, and identification of the primary tumor is essential.Learning points:Learning how to suspect ectopic Cushing syndrome and confirm it among all the causes of excess cortisol.Distinguish between occult and severe ectopic Cushing syndrome and etiology.Providing the adequate treatment of the primary tumor as well as for the cortisol excess.Prognosis depends on the differentiation and type of the primary malignancy.

THIS DYSPNEA FEELS DIFFERENT: A CASE OF DIFFERENTIATION SYNDROME

Vascular handlebar syndrome with blunt injury of the common femoral artery is a rare vascular trauma mechanism, with high possibility of being missed or delayed. We present two cases of vascular handlebar syndrome treated in our hospital and a systematic review of the literature using MEDLINE and SCOPUS databases. Literature review identified 20 similar cases. The median age of patients was 18 years, and in vast majority males in gender. In most cases, the common femoral artery injury was an intimal flap and lumen occlusion with intramural thrombosis followed by transection and intimal injury without occlusion or thrombosis. The median time between injury and diagnosis/treatment was half an hour. Clinical presentation ranged from asymptomatic to acute limb ischemia. The grade of acute ischemia was mostly Rutherford class I (n=14), while acute IIa (n=4), chronic ischemia (n=3), and no ischemia (n=1) were also noticed. The correct diagnosis was revealed by clinical examination only (n=1), or by the combination of clinical and imaging techniques including computed tomography angiography (n=7) and duplex ultrasonography (n=4) or both (n=10). Management of the handlebar trauma syndrome injuries was surgical in most cases. Outcome was favorable in all patients. Vascular handlebar syndrome is extremely rare and high suspicion is required for early diagnosis and definitive treatment, as the early management is effective and crucial for averting the devastating consequences. An individualized approach to the vascular trauma patient is to be applied with considerations taken to the age of the patient, the mechanism of the injury, the anatomy of the lesion, and symptomatology of the case.

“A storm in the middle” evolution of a lateral medullary syndrome to a bilateral medial medullary infarct: A case report