Life events and dementia: what is the nature of their relationship?

The current study analyzed the life events reported by 1271 demented patients vs. 140 cognitively healthy elderly subjects. The Life Change Unit (LCU) method was used to quantify the results. When all the events were included in the analysis, the two groups had similar LCU scores (61.26 vs. 63.42). However, when events causally related to dementia (e.g. stroke) are excluded, demented patients were found to experience half of the LCU load in comparison to controls (30.70 vs. 63.42). In both groups the level of LCU load is far below 100 which is the threshold suggested for the induction of psychosomatic disorders. Conclusively, the current study suggests that there is no causal role for life events in the etiopathogenesis of dementia. On the contrary, demented patients even the last few months before the clinical onset of dementia experience low life-events-related stress, possibly because of subclinical impairment which is already present.     

Trousseau's syndrome - what is the evidence? A population-based autopsy study

Despite numerous studies documenting the association between cancer and venous thromboembolism (VTE), the reason for the excessive risk in certain cancers remains obscure. No large-scale studies have yet investigated the independent effects of cancer type, site and growth pattern. Between 1970 and 1982, 23,796 standardised autopsies were performed, representing 84% of all in-hospital deaths in an urban Swedish population. The relationship between cancer and PE was evaluated with logistic regression. The overall PE prevalence was 23%, and 10% of the population had a fatal PE. Forty-two per cent of pancreatic cancer patients had PE (OR 2.55; 95% CI 2.10-3.09) (p<0.001); gall bladder, gastric, colorectal and pulmonary adenocarcinomas were similarly independently associated with PE. In comparison with squamous cell lung cancer, patients with pulmonary adenocarcinoma had 1.65 times higher odds for PE (95% CI 1.20-2.29). Adenocarcinoma and metastatic cancer were independently associated with PE risk (OR 1.27; 95% CI 1.16-1.40; p<0.001, and OR 1.10;95% CI 1.01-1.20; p=0.024, respectively) but when controlling for cancer type and spread, pancreatic cancer was still associated with an OR of 2.10 (95% CI 1.71-2.58) of PE (p<0.001). We conclude that the risk of PE in cancer patients depends not only on the cancer site and spread but also on the histological type. The excess independent risk in pancreatic cancer is intriguing and should warrant further research.     

CTOs: what is the state of the evidence?

Purpose

Community Treatment Orders (CTOs) require outpatients to adhere to treatment and permit rapid hospitalisation when necessary. They have become a clinical and policy solution to repeated hospital readmissions despite some strong opposition and the contested nature of published evidence. In this article, we appraise the current literature on CTOs from the viewpoint of Evidence-Based Medicine and discuss the way forward for using and researching CTOs.

Results

Non-randomised outcome studies show conflicting results, but their lack of standardisation of methods and measures makes it difficult to draw conclusions. In contrast, all three randomised controlled trials (RCTs) conducted concur in their findings that CTOs do not impact on hospital outcomes. No systematic review or meta-analysis has identified any clear clinical advantage to CTOs.

Conclusion

The evidence-base does not support the use of CTOs in their current form. Involuntary clinical interventions must conform to the highest standard of evidence-based care. To enable clinicians to take an evidence-based approach and to settle remaining uncertainties about the current evidence, high-quality RCTs should be designed and undertaken, using standardised outcome measures.     

Does the right side know what the left is doing?

Following peripheral-nerve lesions there are well-documented events that affect the contralateral nonlesioned structures.These contralateral effects are qualitatively similar to those occurring at the ipsilateral side, but are usually smaller in magnitude and have a briefer time course. It is unclear whether the findings are an epiphenomenon or serve a biological purpose, but in either case the existence of these effects implies the presence of unrecognized signalling mechanisms that link the two sides of the body. Strong circumstantial evidence argues against a peripheral mechanism (for example, via circulating factors) and in favour of a central mechanism, in particular signalling via the system of commissural interneurons that is present in spinal cord and brainstem.While an altered pattern of activity in this system might underlie the phenomenon, there are several reasons for proposing that the changes depend upon chemical signals, possibly growth factors. Because of its relative easy access for experimental manipulation, the spinal cord could serve as a model system to study these transmedian signalling systems.     

Dementia with parkinsonism: what is the diagnosis?

The case presented highlights the difficult differential diagnosis of dementia with parkinsonism. Many disorders affecting the frontal-subcortical circuits produce the triad of impaired cognition, movement disorder, and neuropsychiatric symptoms. The 72-year-old patient whose case is reviewed here had abnormalities in all three domains.     

Longitudinal MRI study of multiple system atrophy – when do the findings appear,and what is the course?

Several investigators have revealed features of multiple system atrophy (MSA) by magnetic resonance imaging (MRI). For use in clinical diagnosis, we determined the exact time when two main features of pontine and putaminal intensity changes appeared. Furthermore, in order to reveal the course from when the disorder first appeared and how it spread, we also investigated the course of MRI findings and differences between clinical subtypes. The cranial MRI of 42 patients with MSA were longitudinally studied including comments on the so called “cross sign” of pontine T2 high intensity, which was divided into 6 stages, and also on the linear T2 high intensity of the dorsolateral side of the putamen (“putaminal slit”) which was divided into 4 stages. Patients were classified as 16 MSA-C, 7 autonomic dominant type (MSA-A), and 19 MSA-P. The age at onset ranged from 41 to 74 years (mean, 55 ± 9). The duration of the disease in the MRI study ranged from 1 to 24 years. The pontine “cross sign” was completed (shows Cross, stage IV) earlier in MSA-C mainly before 5 years, later in MSA-P and even much later in MSA-A. Regarding the “putaminal slit”, MSA-P shows earlier bilateral changes (stage II), mostly before 3 years, compared with MSA-C, which requires 4 years to reveal even a unilateral change (stage I), or MSA-A which requires even more time. MRI findings showed a tendency to relate to clinical findings, since MSA-C exhibits “cross sign” completion earlier than bilateral “putaminal slit”; however, MSA-P shows bilateral “putaminal slit” earlier than “cross sign”, and MSA-A requires much more time to show both. Clinically, MSA-C, MSA-A, or MSA-P showed different MRI courses so that three subtypes could be defined also with MRI findings. Therefore these observations are useful not only for diagnosis of MSA itself, but also to distinguish clinical subtypes (MSA-C, MSA-A, or MSA-P) which have different rates of lesion progression. Received: 5 September 2001, Received in revised form: 10 December 2001, Accepted: 17 December 2001     

Prion diseases: what is the neurotoxic molecule?

A great deal of effort has been devoted during the past 20 years to defining the chemical nature of prions, the infectious agents responsible for transmissible spongiform encephalopathies. In contrast, much less attention has been paid to elucidating how prions actually damage the central nervous system. Although it is commonly assumed that PrP(Sc), the protein constituent of infectious prions, is the primary culprit, increasing evidence indicates that this may not be the case. Several alternative molecular forms of PrP are reasonable candidates for the neurotoxic species in prion diseases, although it is still too early to tell whether these or other ones will turn out to be the true instigating factors. The cellular pathways activated by neurotoxic forms of PrP that ultimately result in neuronal death are also being investigated, and several possible mechanisms have been uncovered, including the operation of quality control processes in the endoplasmic reticulum. Elucidating the distinction between the infectious and neurotoxic forms of PrP has important implications for designing therapy of prion diseases, as well as for understanding pathogenic mechanisms operative in other neurodegenerative disorders and the role of prion-like states in biology.     

Childhood epilepsy: what is the evidence for what we think and what we do?

This article reviews the strength of the evidence that underlies the current approach to the management of childhood epilepsy. The authors reviewed published, peer-reviewed English literature accessed through PubMed and Cochrane reviews with evidence rated as Class 1 (strongest) to Class 4 (weakest). There is considerable inaccuracy in the diagnosis of seizures and epilepsy syndromes. Sound information supports the consensus that the diagnosis of epilepsy should await two unprovoked seizures. Population-based studies indicate that remission from childhood onset epilepsy occurs in at least 50% of children. It is easier to predict a good seizure outcome than a poor one. Absence of concomitant neurologic handicap and onset before about 12 years of age are the most consistent predictors of remission. Intractability is poorly defined and difficult to predict until several antiepilepsy drugs have been used and failed to control the seizures. Most epilepsy syndrome diagnoses do not yield an accurate prognosis. Social outcome appears unsatisfactory in about 50% of cases without intellectual handicap. Death is rare in childhood epilepsy. Those without severe neurologic handicaps have the same mortality as the general population. We identified only 27 published randomized trials of antiepilepsy drugs in children that compare the efficacy of antiepilepsy drugs, offer treatment of syndromes currently without successful treatment, or have negative effects. There is a pressing need for better definitions of seizures and epilepsy syndromes. The causes of poor social outcome are unclear. Intractability needs a clear definition and randomized trials comparing treatment regimes are sadly lacking.     

Detection of dementia in primary care: the Linköping study

We examined to what extent dementia and cognitive impairment are detected in a primary health care centre. A systematic sample of patients aged 70 years and above, who attended a primary health care centre for a doctor's consultation (n = 350) were examined with a neuropsychiatric examination and an interview with a close informant. Dementia was diagnosed according to DSM-III-R. Medical records from the health centre were examined for entries on cognitive decline or dementia, other diagnoses and prescribed drugs. The prevalence of dementia was 16.3% and a further 3.1% had questionable dementia. Cognitive disturbances or dementia were noted in case records in 15 out of 57 (26%) demented cases, and in 1 out of 11 (9%) questionable dementias. Compared to non-demented patients, the demented had more diagnoses and a higher number of prescribed drugs. Severity and duration of dementia were associated with an increased detection.     

Drug addiction, anorexia: what is the connection?

Drug addictive and anorexic behaviours come from a same desire to reach an eventual autonomy. Drug addicts and anorexic people fight against dependency by instituting a new dependency, the one which ties them up to their behaviours; nevertheless this substitution from one dependency to another one does not happen by chance, it is chosen by these adolescents in order to allow them a possible structuring modification. These latter having difficulties to internalize "the father's law" in a certain way prepare the ground on which the law will become real by setting up a new alienating situation. In a way, drug addictive and anorexic behaviours carry out a "paternal metaphor" that is to say a metaphor which substitutes the "no of the father" to the place first symbolized by the operation of the mother's absence.