Multimodal neurophysiological evaluation of primary progressive multiple sclerosis - An increasingly valid biomarker, with limits.

BACKGROUND: The promising utility of multi-modality evoked potential batteries to objectively measure multi-tract dysfunction has been evaluated by several groups using different methods. OBJECTIVE: To independently evaluate the use of multi-modality evoked potential batteries as surrogate biomarkers for both physical and cognitive status in a cohort of Primary Progressive Multiple Sclerosis patients and identify the most potentially useful scoring method of those described. METHODS: 28 Patients with Primary Progressive Multiple Sclerosis underwent clinical evaluation with Kurtzke's Modified EDSS and the Multiple Sclerosis Functional Composite (MSFC). 19 Participants also underwent the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Visual, Brainstem Auditory, Somatosensory and Motor Evoked Potentials were recorded on all. Results were graded by variants of the Global Evoked Potential Score, Multiple Evoked Potential Score and Summation of Z transformed Evoked Potential Latencies for correlation against the clinical scores. CONCLUSIONS: Multi-modal evoked potential batteries generally show moderate and useful correlation with clinical status as measured by the regulatory standard of EDSS (r = .65 vs. mEPS p < .005) and MSFC (r = .39 vs. mEPS p < .05). The graded qualitative mEPS scoring system displayed the strongest relationship although the influence of scoring system applied appeared reassuringly minimal. Non-association with cognitive impairment is an important limitation however.

Communication and consent: discussion and organ donation decisions for self and family.

BACKGROUND: Organ transplantation is a significant medical advancement. However, number of individuals registering as donors and next-of-kin's refusal to grant consent are notable limitations on the availability of organs for transplantation. Therefore, investigation into factors that influence willingness to donate and consent decisions is warranted. We examined the relationship between attitudes and family communication in relation to consent decisions for self and family member organ donation (OD). Data were collected from students at an Australian university and individuals from the wider community (N = 267). METHOD: Participants completed an on-line survey composed of questions relating to demographic information, questionnaires from previous research, and several single items relating to family communication and consent created specifically for the study. The main outcome measure was participants' willingness to consent to OD for themselves or for a family member. RESULTS: Attitudes and prior discussion of OD were predictive of registration and willingness to consent. Positive attitudes were also related to previous conversations regarding OD. A more open level of communication within families was associated with an increased tendency to discuss OD, but was not directly related to consent decisions. CONCLUSION: Findings reiterate the importance of promoting positive attitudes within the community and specific, informed discussion within families. The positive influence these factors exert on next-of-kin decisions may be vital to maximize donation rates in opt-in systems (such as Australia).

Coping response and survival in breast cancer patients: a new analysis.

PURPOSE: The purpose of this study was to analyse the impact of coping response on survival of breast cancer by using a new method of assessing coping. METHOD: Adjustment to cancer was assessed using a revised measure in a large cohort of breast cancer patients (N = 578) followed up over a period of 10 years. Impact of coping response measured early in the disease process (<4 months from primary diagnosis of early-stage breast cancer) was assessed, and survival analyses were undertaken including known clinical staging data and cancer treatment details. RESULTS: After 5 years of follow-up from primary diagnosis, the effect of prior 'negative adjustment' was statistically significantly linked to increased risk of death and relapse of breast cancer, and for the 10-year analysis, this result remained for both risk of death and relapse. There was no statistically significant effect on survival of the novel 'positive adjustment' response. CONCLUSIONS: Coping with cancer was assessed using a new methodology and is linked to an adverse impact of negative adjustment on overall survival. Positive adjustment was unrelated to survival. The current study strengthens previous evidence that there is a link between survival and coping response. The question remains of how coping response might affect physical outcome. It is considered that coping response likely impacts survival through the mediating effects on lifestyle and health behaviour that may contribute to an adverse prognosis.

Subjective cognitive complaints at menopause associated with declines in performance of verbal memory and attentional processes.

BACKGROUND: Subjective cognitive complaints are commonly reported during the menopause transition. Whether they are indicative of actual cognitive impairment is unknown. OBJECTIVES: To assess subjective attention and memory complaints in a general population sample across the stages of menopause; to assess relationships between subjective complaints and objective measures of cognitive performance; to examine potential menopause-related, hormonal, psychosocial and cognitive predictors of subjective complaints. METHODS: Multivariate and univariate analyses of cross-sectional data from 120 pre-, peri- and postmenopausal women. RESULTS: Attention problems were more evident in the perimenopausal and hormone therapy groups. Subjective cognitive problems were associated with declines in verbal memory, and with declining performance on reaction time measures of attention, with small-to-medium effect sizes. Predictors of subjective complaints included menopause-related symptoms, psychosocial variables, psychological symptoms and objective cognitive performance. CONCLUSION: A link has been demonstrated between the subjective and objective aspects of cognitive function in association with the menopausal transition. It is suggested that greater recognition be given to cognitive symptoms as forming part of the constellation of menopause-related symptoms.

Mental Adjustment to Cancer Scale: psychometric properties in a large cancer cohort.

OBJECTIVES: The Mental Adjustment to Cancer (MAC) Scale is widely used to assess psychological response to cancer. There have been several attempts to replicate independently the original factor structure of the MAC. Evidence from these replication studies is reviewed. A re-analysis of the MAC Scale was conducted on a substantial new cohort in order to clarify the factor structure. METHODS: 1255 patients with various cancer diagnoses completed the MAC Scale. RESULTS: Two results emerged: first, that the original MAC dimension of Helplessness/Hopelessness is extremely stable and robust; second, that the original factors can be subsumed within two overarching (first order) factors relating to positive and negative adjustment scores. CONCLUSIONS: The original MAC Scale remains a satisfactory measure of psychological outcome. Two-higher order factors representing global adjustment are now available to provide an overall summary measure alongside the original specific sub-scales.

A comparison of community, clinician, and patient preferences for naming a cancer-related mutation.

This study compared language preferences to describe a cancer-related mutation in three groups: 253 members of the general community, 20 clinicians working in cancer genetics, and 269 individuals at increased risk of carrying a cancer-related mutation (including 198 women with a strong family history of breast and/or ovarian cancer, and 71 individuals with a family history of hereditary non-polyposis colorectal cancer). In the community sample, 'faulty gene' was the preferred term to describe a cancer-related mutation, although females, those affected by cancer and those who felt cancer had a large impact on their lives were more likely to prefer the terms 'gene change' or 'altered gene'. In contrast, the clinicians' preference ratings for 'faulty gene' and 'gene change' were equal. When forced to choose between 'faulty gene' and 'altered gene', the high-risk patient group reported preferring 'faulty gene', although over 40% were happy with either term. Further research investigating individuals' understanding of the different terms that can be used to describe a cancer-related mutation, and the functional impact of these terms on patients' thoughts and feelings about their condition and on their health-related behavior after genetic counseling would be worthwhile.

Case of the month: A case of airway obstruction following tenecteplase administration.

The value of thrombolysis in the treatment of acute myocardial infarction is well established. Haemorrhage into subcutaneous tissues is fortunately a rare complication of fibrinolytic administration. However, if as a result of trauma a haematoma develops within the neck following thrombolysis, it can lead to rapid airway compromise. This is the first reported case of tenecteplase administration leading to subcutaneous haemorrhage and consequent airway compromise. It is also the first reported case where the antecedent trauma was a jaw thrust.

Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery alone in resected gastric cancer. A combined analysis of the EORTC GI Group and the ICCG.

BACKGROUND: In patients who underwent radical resection for gastric cancer, we investigate the relative efficacy of combined 5-fluorouracil+adriamycin or epirubicin and methotrexate with leucovorin rescue (FAMTX or FEMTX) compared with a control arm. PATIENTS AND METHODS: This report is a prospective combined analysis of two randomized clinical trials conducted on patients who underwent radical resection for histologically proven adenocarcinoma of the stomach or esophago-gastric junction. Three hundred and ninety-seven untreated patients, 206 from 23 European Organization for Research and Treatment of Cancer (EORTC) institutions and 191 from 16 International Collaborative Cancer Group (ICCG) institutions, were randomized. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and the treatments were compared for these end-points by means of the log-rank test, retrospectively stratified by trial. RESULTS: In a planned combined analysis of the two trials, no significant differences were found between the treatment and control arms for either DFS (hazards ratio: 0.98, P=0.87) or OS (hazards ratio: 0.98, P=0.86). The 5-year OS was 43% in the treatment arm and 44% in the control arm and the 5-year DFS was 41% and 42%, respectively. CONCLUSION: Neither FAMTX nor FEMTX can be advocated as adjuvant treatment in patients who undergo resection for gastric cancer.

Does genetic counseling have any impact on management of breast cancer risk?

Despite there being an increasing literature on the impact of cancer genetic counseling on risk perception and mental health, there is a lack of data describing impact on risk management. Genetic counseling and testing for cancer predisposition genes aims to improve the future health of those at high risk through appropriate surveillance and screening. However, management of breast cancer risk in women with a family history of this disease is an area of controversy. Counseling services may recommend specific risk management options to women, who then rely on their local screening service to make provision. This study investigated the impact of genetic counseling on management of breast cancer risk in women attending Cancer Family Clinics. A total of 293 women attending four genetic clinics were enrolled. Rates of breast self-examination, clinical breast examination, mammography, biopsy, detected cancers, and other screenings were documented. Participants' perceived benefits and barriers to mammography were assessed along with cancer worry. Results show that rates of mammography, clinical breast examination, and breast self-examination were increased following clinic attendance (p < 0.001). Women in the under 35 age-group had limited access to screening. Rates for biopsy and detected cancers were low. Women reported positive attitudes to mammography, with few reported barriers. Contrary to previous studies, there was no evidence that anxiety about breast cancer impedes uptake of health surveillance methods. Genetic counseling had a positive impact on management of breast cancer risk. Whether this translates into future health gains remains to be established.

Adverse impact of bone marrow transplantation on quality of life in acute myeloid leukaemia patients; analysis of the UK Medical Research Council AML 10 Trial.

The increasing success of intensive consolidation chemotherapy (CCT) as an alternative to bone marrow transplant (BMT) in acute myeloid leukaemia (AML) necessitates comparison of the impact on quality of life (QoL) of these two treatment modalities. Most QoL studies following BMT involve small patient numbers and provide ambivalent results. The present study examines QoL in a large number of patients 1 year from the end of treatment within the United Kingdom Medical Research Council (UK MRC) AML10 trial of BMT versus CCT. Allogeneic-BMT (Allo-BMT) was observed to have an adverse impact on most QoL dimensions compared with Autologous-BMT (A-BMT) and CCT. More patients receiving BMT had mouth dryness problems and worse sexual and social relationships, professional and leisure activities than CCT patients. QoL in A-BMT patients was less impacted than Allo-BMT. Intention-to-treat analysis showed similar results. These results indicate that a reconsideration of treatment strategies is warranted, and that further, good prospective studies are needed to evaluate more clearly the effects of these treatments in long-term survivors.

Development of a disease specific questionnaire to supplement a generic tool for QoL in colorectal cancer.

The need for disease-specific quality of life measures is highlighted in the literature. The psychometric properties of a supplementary disease-specific quality of life questionnaire developed for use with a generic Quality of Life tool in colorectal cancer patients are explored. Originally developed and tested in a German sample, the English translation was tested on a cohort of UK colorectal cancer patients. Relevance and acceptability was previously established in Germany. A rigorous factor analysis ascertained the underlying structure of two factors with a number of single items that were retained as clinically important symptom indicators. In considering validity, four conditions were assessed: Reliability using Cronbach's alpha; Construct validity by comparing patient subgroups; Clinical Validity, by testing the hypothesis that some patient subgroups experience worse quality of life; Construct Reliability using second order factor analysis with the EORTC QOLQ-C30 scales, confirming that the factors retained provide an excellent measure of physical discomfort and a good measure of physical well being. Two other such questionnaires were developed in parallel with this one and reported in the literature (FACT-C and QOLQ-CR38). However, this questionnaire provides a useful alternative tool for use in clinical trials of colorectal cancer treatments alongside a core QoL questionnaire especially when brevity is an important consideration.

Neuropsychological sequelae of bilateral posteroventral pallidotomy.

OBJECTIVES: To document the impact of bilateral posteroventral pallidotomy on cognitive status. METHODS: 17 patients with Parkinson's disease were evaluated with a neuropsychological battery before and six months after bilateral pallidotomy. A comparison group (n = 8) was also assessed at six month intervals. Outcome variables were tests of memory, language, visuospatial function, attention, executive skills, and depression. RESULTS: Despite a large number of variables studied, a significant postsurgical change was found only in performance of the tower of London task, a measure of planning abilities. The effect size of this change was larger than that of the comparison group, and a reliable change index score established that 5 of 13 surgical patients had statistically reliable reductions in planning performance. CONCLUSIONS: Patients with a young age of onset and long duration of Parkinson's disease who underwent bilateral pallidotomy had a relatively circumscribed reduction in neuropsychological functioning, being limited to motor planning efficiency. These data suggest that the cognitive role of the posteroventral globus pallidus is limited, at least in people with Parkinson's disease.

Differences in naming accuracy of odors presented to the left and right nostrils.

Two interlinked areas of debate within psychology are the existence of hemispheric specialization for olfactory processing and whether odors are processed primarily as perceptual codes or as a set of semantic features. This study compared accuracy in naming and judgments of familiarity by right handed subjects to common odors that were presented to the left or right nostrils. There was significantly better production of the correct name of the odor after left side presentation, than after right. Familiarity ratings were identical.

Second generation effects of maternal alcohol consumption during pregnancy in rats.

1. Previous studies have shown that when female rats are administered alcohol during pregnancy there are adverse effects on their progeny, including decreased birth weight and delayed neuromotor development. Evidence from several sources suggests alcohol exposure may contribute to cytogenetic abnormalities, suggesting the possibility of cross generational effects from prenatal exposure. 2. On day 1 of gestation female rats were randomly allocated to the Alcohol group, which received a liquid diet containing 5% (v/v) ethanol solution until parturition, the Sucrose control group, which received an identical diet, except that sucrose had been isocalorically substituted for ethanol, or the Chow control, which received standard laboratory chow. 3. When the offspring of these rats reached adulthood they were mated with drug-free rats and the development of their offspring was monitored. 4. In comparison with female pups whose sires had been exposed to alcohol in utero, the weight of pups descended from fetally-exposed dams increased more slowly from day 1 to day 7. 5. At five days of age, significant differences favouring the two control groups were found in latency to right for pups descended from fetally-exposed dams. 6. These data suggest that the effects of prenatal exposure to alcohol are more pervasive than previously thought and affect female pups to a greater extent than males.

Thiamin deficiency and Korsakoff's syndrome: failure to find memory impairments following nonalcoholic Wernicke's encephalopathy.

Prolonged alcohol consumption is associated with a variety of neuropsychiatric conditions, including the dense amnesic disorder known as Korsakoff's syndrome. Korsakoff's syndrome is frequently diagnosed in alcoholics after an episode of acute thiamin deficiency. The accepted view within the medical literature is that the etiology of this disorder lies in thiamin deficiency or Wernicke's encephalopathy. However, examination of the published reports of pure thiamin deficiency unaccompanied by chronic and excessive consumption of alcohol shows that, in this group of patients, the rate of progression to Korsakoff's syndrome is low. This result suggests that the memory impairments associated with alcohol-related brain damage cannot be attributed to thiamin deficiency alone. The etiology of alcohol-related cognitive impairments such as Korsakoff's syndrome is still poorly understood but several lines of evidence suggest multiple causal factors interact to produce deficits in performance. Animal models that manipulate only a single putative etiological factor are unlikely to elucidate the multiple influences that lead to Korsakoff's syndrome. A study of the natural history of alcohol-related brain damage is needed that will allow an assessment of individual risk factors and their interactions.

The effects of single and repeated episodes of thiamin deficiency on memory in alcohol-consuming rats.

The underlying pathogenesis of Korsakoff's syndrome, an amnesic disorder most commonly found in alcoholics, is not well understood. Chronic alcoholism is associated with thiamin deficiency and current thinking is that this may be the causal factor. In Experiment 1, rats were given a 20% (v/v) ethanol/water mix as their only source of fluid for 156 days. Three groups were made thiamin deficient through the combination of a thiamin-deficient diet and the centrally acting thiamin antagonist pyrithiamin hydrobromide, after 4, 15, and 26 weeks exposure to ethanol, respectively. The control group was given ad lib access to laboratory chow and water throughout this period. There were no differences between groups on either the working or reference versions of the Morris water tank paradigm. In Experiment 2, to test the hypothesis that a single bout of thiamin deficiency, with or without concurrent alcohol intake, is not sufficient to cause severe memory impairments, two groups of rats were subjected to three bouts of thiamin deficiency. One of these groups consumed an ethanol/water mix, the other tap water. A third group was made thiamin deficient on only one occasion. The control group was not made thiamin deficient and consumed lab chow and tap water throughout. Once again, there were no between-group differences in the data derived from testing in either the eight-arm radial maze or the Morris water tank task. These experiments indicate that the aetiology of Korsakoff's syndrome is more complex than previously thought.