However, core features of NMS were observed significantly more often among cases meeting diagnostic criteria. Individual symptoms

were also described in suspected cases that did not meet diagnostic criteria. These findings suggest a continued need for consensus on standard criteria for NMS. Keywords: neuroleptic malignant syndrome, antipsychotics, side effect, diagnostic criteria, extrapyramidal syndrome, creatine kinase Introduction Neuroleptic malignant phase 3 syndrome (NMS) is a rare and potentially fatal complication of treatment with antipsychotics [Strawn et al. 2007], which is characterised by four domains Inhibitors,research,lifescience,medical of signs and symptoms: rigidity, fever, dysfunction of the autonomic nervous system and alterations in consciousness. Researchers and clinicians face the difficulty of distinguishing its signs and symptoms not only from the Inhibitors,research,lifescience,medical mental disorder being treated but also from common side effects of psychotropic

medication. Moreover, scientific identification of cases is made difficult by its nature as a diagnosis of exclusion with many conditions, common and rare, in the differential. Despite some evidence for a broad consensus on NMS [Strawn et al. 2007, 2008], much remains controversial Inhibitors,research,lifescience,medical and obscure about the aetiology, pathophysiology and treatment [Picard et al. 2008; Margetić and Aukst Margetić, 2010] of this condition which is ‘heterogeneous in onset, presentation, progression and outcome’ [Strawn et al. 2007]. Diagnosis remains similarly controversial, several criteria having been proposed with Inhibitors,research,lifescience,medical different conceptual commitments,

forms and functions. Gurrera and colleagues’ meta-analysis of incidence studies found five published diagnostic criteria, two modifications of Inhibitors,research,lifescience,medical previously published criteria, and a further four idiosyncratic and four undisclosed sets distributed among 26 eligible studies published between 1960 and 2003 [Gurrera et al. 2007]. Although they found no association between stringency of criteria and estimated incidence, this is likely to be due to the lack of power afforded by typical case numbers. Adityanjee and Regorafenib side effects colleagues reviewed the existing criteria in 1999, discussing or mentioning some 17 sets, or modifications of sets, of criteria [Adityanjee et al. 1999]. They divided these into six groups: Levenson [Levenson AV-951 1985, 1986]; Addonizio and colleagues [Addonizio et al. 1986]; Pope and colleagues [Pope et al. 1986; Keck et al. 1989]; Adityanjee and colleagues [Adityanjee et al. 1988]; Friedman and colleagues [Friedman et al. 1988]; Caroff and colleagues [Lazarus et al. 1989; Caroff et al. 1991; Caroff and Mann, 1993], classifying Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for NMS [American Psychiatric Association, 1994] as a modified version of these. The authors of this review further proposed a more stringent set of research diagnostic criteria.