When considering previous research, it is important to remember that our study is different in terms of case finding and statistical techniques. Gurrera and colleagues performed a retrospective analysis of medical notes derived exclusively from inpatients who had been referred to a consultation service over a period of 6 years. These authors found 64 patients in whom NMS was a differential diagnosis at the time of referral (corresponding Inhibitors,research,lifescience,medical to our definition of ‘suspected NMS’). However, they excluded clinical findings when an alternative ‘non-NMS cause’ was possible, which produced a group of 45 patients, with 65 possible episodes of NMS. While the

stringency of their inclusion criteria was designed to reduce the number of false positives, ours was designed to allow the constraints of a retrospective case review to provide a more naturalistic picture of what clinicians consider as possible episodes of NMS. Difficulties in diagnosing NMS should not inhibit PR-619 molecular weight research into this condition, Inhibitors,research,lifescience,medical which already presents challenges because of its rarity. Disagreements between the criteria and the relatively large number of people with at least some degree of symptomatology who do not fulfil diagnostic Inhibitors,research,lifescience,medical criteria suggest that it may be better to consider NMS as a spectrum of complications, possibly

with clinical and subclinical states. Of potential relevance here is Inhibitors,research,lifescience,medical the improved profile of positive predictive values for a number of NMS-relevant symptoms when the broader probable criteria of Pope and colleagues [Pope et al. 1986] were included with the other criteria, although inevitably the analyses of screening properties of symptom counts involves a circular argument (analysing numbers of symptoms rather than the criteria based around those symptoms). A considerable degree of disagreement may lie simply in controversy Inhibitors,research,lifescience,medical over semantics between authors with respect to symptoms essential for diagnosis and how the symptoms are defined for practical purposes in research,

rather than actual features of the disorder. Therefore, ways of characterising the disorder below more robustly and with less ambiguity are needed. However, it should also be borne in mind that the core symptoms of NMS are, when present in isolation, relatively nonspecific and may have alternative aetiologies. Higher vigilance, and possibly the increased availability of rapid chemical pathology resources for mental health teams, may mean that NMS as seen in clinical services is more often detected at prediagnostic stages. It is possible that research diagnostic criteria and approaches may have to change to reflect this. Further evaluation is clearly required and the relatively holistic approach to case ascertainment used here should be helpful to others who are working in this field.