Subarachnoidal release of inflammatory cytokines (interleukin (IL)-1 , IL-6, and tumour necrosis factor (TNF)-) was characterised in 35 patients with subarachnoid haemorrhage (SAH) and control subjects and compared with development of complicating haemodynamic abnormalities in basal cerebral arteries and clinical outcome. Serial analysis allowed the observation of a subacute response profile of these key mediators of inflammation in the subarachnoidal space. This compartmentalised inflammatory host response was closely associated in time and extent with development of increased blood flow velocities in the basal cerebral vessels as recorded by transcranial Doppler sonography. Moreover, intrathecal secretion of inflammatory cytokines was significantly increased in patients with poor clinical outcome. Together, these findings suggest a role of excessive compartmentalised inflammatory host response in pathogenesis of cerebrovascular complications after SAH. (J Neurol Neurosurg Psychiatry 2001;70:534-537) Keywords: subarachnoid haemorrhage; inflammatory cytokines; cerebral blood flow; vasospasm; cerebral ischaemia Subarachnoid haemorrhage (SAH) most commonly occurs when an aneurysm in a basal cerebral artery ruptures. Among patients who survive this event, the leading cause of death and disability is subsequent constriction of the large cerebral arteries causing delayed cerebral ischaemia, the "second stroke". 1 2 Monitoring of cerebral blood flow velocities (CBFVs) in the large pial arteries identifies patients with SAH with raised risk for ischaemic complications. [3][4][5][6] In SAH, it has been shown in multiple studies that CBFVs on transcranial Doppler sonography are inversely related to vessel diameters on angiography. [3][4][5][6] The noninvasive character of this technique enables serial investigations of developing haemodynamic abnormalities in an individual patient.Earlier studies described inflammatory changes in SAH-that is, subarachnoidal and perivascular leucocytic infiltrates in the subarachnoidal space 7-9 in relation to development of cerebral vasospasms. 8 9 Moreover, the proinflammatory cytokines interleukin (IL)-1 , IL-6, and tumour necrosis factor (TNF)-that orchestrate the cascade of inflammatory host response to infection and tissue damage 10 11 have been detected in the CSF of patients with SAH. [12][13][14][15][16] These earlier findings suggest an inflammatory pathogenesis of vasospasms in SAH. In this study, we tested the hypothesis that the extent and pattern of secretion of key mediators of inflammation IL-1 , IL-6, and TNFare associated with development of haemodynamic abnormalities in basal cerebral arteries and with clinical outcome. Patients and methods PATIENTS AND CONTROL SUBJECTSThirty five patients (21 women and 14 men), aged between 23 and 76 (median 56) years with SAH caused by aneurysmal rupture and presenting within 48 hours after onset of first symptoms were studied. Hunt and Hess scores to classify disease severity were 1 in 9%, 2 in 11%, 3 in 32%, 4 in 29%, and...

BackgroundDelirium is a common and serious problem among acutely unwell persons. Alhough linked to higher rates of mortality, institutionalisation and dementia, it remains underdiagnosed. Careful consideration of its phenomenology is warranted to improve detection and therefore mitigate some of its clinical impact. The publication of the fifth edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-5) provides an opportunity to examine the constructs underlying delirium as a clinical entity.DiscussionAltered consciousness has been regarded as a core feature of delirium; the fact that consciousness itself should be physiologically disrupted due to acute illness attests to its clinical urgency. DSM-5 now operationalises ‘consciousness’ as ‘changes in attention’. It should be recognised that attention relates to content of consciousness, but arousal corresponds to level of consciousness. Reduced arousal is also associated with adverse outcomes. Attention and arousal are hierarchically related; level of arousal must be sufficient before attention can be reasonably tested.SummaryOur conceptualisation of delirium must extend beyond what can be assessed through cognitive testing (attention) and accept that altered arousal is fundamental. Understanding the DSM-5 criteria explicitly in this way offers the most inclusive and clinically safe interpretation.

Delirium occurring in patients with dementia is referred to as delirium superimposed on dementia (DSD). People who are older with dementia and who are institutionalized are at increased risk of developing delirium when hospitalized. In addition, their prior cognitive impairment makes detecting their delirium a challenge. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision are considered the standard reference for the diagnosis of delirium and include criteria of impairments in cognitive processes such as attention, additional cognitive disturbances, or altered level of arousal. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision does not provide guidance regarding specific tests for assessment of the cognitive process impaired in delirium. Importantly, the assessment or inclusion of preexisting cognitive impairment is also not addressed by these standards. The challenge of DSD gets more complex as types of dementia, particularly dementia with Lewy bodies, which has features of both delirium and dementia, are considered. The objective of this article is to critically review key elements for the diagnosis of DSD, including the challenge of neuropsychological assessment in patients with dementia and the influence of particular tests used to diagnose DSD. To address the challenges of DSD diagnosis, we present a framework for guiding the focus of future research efforts to develop a reliable reference standard to diagnose DSD. A key feature of a reliable reference standard will improve the ability to clinically diagnose DSD in facility-based patients and research studies.