Minor physical anomalies in autism: a meta-analysis.

Autism is a complex neurodevelopmental disorder in which the interactions of genetic, epigenetic and environmental influences play a causal role. Despite the compelling evidence for a strong heritability, the etiology and molecular mechanisms underlying autism remain unclear. High phenotypic variability and genetic heterogeneity confounds the identification of susceptibility genes. The lack of robust indicators to tackle this complexity in autism has led researchers to seek for novel diagnostic tools to create homogenous subgroups. Several studies have indicated that patients with autism have higher rates of minor physical anomalies (MPAs) and that MPAs may serve as a diagnostic tool; however, the results have been inconsistent. Using the cumulative data from seven studies on MPAs in autism, this meta-analysis seeks to examine whether the aggregate data provide evidence of a large mean effect size and statistical significance for MPAs in autism. It covers the studies using multiple research methods till June 2007. The current results from seven studies suggested a significant association of MPAs in autism with a robust pooled effect size (d=0.84), and thereby provide the strongest evidence to date about the close association between MPAs and autism. Our results emphasize the importance of MPAs in the identification of heterogeneity in autism and suggest that the success of future autism genetics research will be exploited by the use of MPAs. Implications for the design of future studies on MPAs in autism are discussed and suggestions for further investigation of these important markers are proposed. Clarifying this relation might improve understanding of risk factors and molecular mechanisms in autism.

Changes in functional outcome and quality of life in patients and caregivers after aneurysmal subarachnoid hemorrhage.

OBJECT: Although the case-fatality rate after subarachnoid hemorrhage (SAH) does not change considerably after the first 4 weeks, functional outcome and the quality of life (QOL) may. To assess the extent of changes in functional outcome and QOL after SAH, the authors conducted a follow-up study at 18 months in patients and caregivers who had participated in a previous study of QOL 4 months after SAH. METHODS: In a consecutive series of 98 patients admitted with SAH, 68 had survived until 4 months postbleed, at which time an initial outcome assessment had been performed in 64 of them. This series of 64 patients was contacted again at a median of 18 months after SAH. In all patients, functional outcome was assessed by means of the modified Rankin Scale (mRS). In 48 patients and 35 caregivers QOL was assessed using the SF-36, the Sickness Impact Profile (SIP), and a visual analog scale. The results were compared with the scores that had been obtained at 4 months after SAH. Thirty-two patients (50%) had improved at least one point on the mRS, in 23 patients functional outcome had remained unchanged, six patients had deteriorated one point on the mRS, and three had died. No major changes in the QOL of patients and caregivers could be found on the SIP, but on the SF-36 an improved QOL was detected in patients with better Rankin grades. On both instruments, the QOL at 18 months was still reduced compared with the reference population in all patients. CONCLUSIONS: Functional outcome improves significantly between 4 months and 18 months post-SAH; studies on functional outcome after SAH can be compared only if outcome is assessed at the same time interval. The improved functional outcome seems to be accompanied by an improved QOL.

Quality of life in patients with axonal polyneuropathy.

"Quality of life" (QOL) measurement reflects the impact of a disease on the daily life of a patient, and this can be used as an outcome measure in clinical trials. QOL measurements are rarely used in patients with neuromuscular disease. The aim of this study was to determine whether QOL is reduced in chronic polyneuropathy, whether there is a relationship between QOL and objective measures of disease severity, and whether measuring QOL is a useful addition to the assessment of severity of polyneuropathy. We measured QOL in 90 patients with chronic axonal polyneuropathy (33 with hereditary motor and sensory neuropathy type II and 57 with chronic idiopathic axonal polyneuropathy) using the RAND 36-item Health Survey questionnaire (RAND-36). We compared the results with the QOL of a reference population, with summed motor and sensory scores, and with the Rankin scale for handicap. Patients had worse scores than the reference population on seven of eight areas of the RAND-36. Patients with both low motor and low sensory scores rated lower in physical and emotional areas than less impaired patients. A low Rankin score was related only to physical domains. We conclude that in patients with chronic axonal polyneuropathy the severity of disease can be assessed with a general QOL instrument, and that this provides additional information, particularly on areas related to emotional and social functioning.

Randomized pilot trial of postoperative aspirin in subarachnoid hemorrhage.

OBJECTIVE: To assess the safety and feasibility of a clinical trial on the effectiveness of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH). BACKGROUND: Several studies have indicated that increased platelet activity might be involved in the pathogenesis of delayed cerebral ischemia (DCI) after SAH. METHOD: Fifty patients who had early surgery (< or =4 days) for a ruptured aneurysm were enrolled in this randomized, double-blind, placebo-controlled trial. Trial medication, consisting of suppositories with 100 mg ASA versus placebo, was started immediately after surgical clipping of the aneurysm and continued for 21 days. End points were functional outcome and quality of life at 4 months, clinical deterioration after operation, development of DCI, hypodense lesion on postoperative CT, and hemorrhagic complications. RESULTS: One-third of all patients with aneurysmal SAH were eligible for the trial. Fifteen of 26 patients receiving placebo deteriorated clinically versus 10 of 24 patients receiving ASA; 4 patients in each group deteriorated from DCI. Postoperative hypodensities on CT were observed in 27 patients, distributed equally in both groups. Functional outcome and quality-of-life scores were slightly in favor of patients who had received ASA, but not to a significant degree (p = 0.22). Two patients in the ASA group had an asymptomatic hemorrhagic complication, and one patient in the placebo group had a fatal and another a symptomatic hemorrhagic complication. CONCLUSION: This pilot study shows that a clinical trial of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH) is feasible and probably safe. The effectiveness of ASA on functional outcome and delayed cerebral ischemia has to be studied in a larger trial.

Initial loss of consciousness and risk of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage. We studied the prognostic value for DCI of 2 factors: the duration of unconsciousness after the hemorrhage and the presence of risk factors for atherosclerosis. METHODS: In 125 consecutive patients admitted within 4 days after hemorrhage, we assessed the presence and duration of unconsciousness after the hemorrhage, the neurological condition on admission, the amount of subarachnoid blood, the size of the ventricles, and a history of smoking, hypertension, stroke, or myocardial infarction. The relationship between these variables and the development of DCI was analyzed by means of the Cox proportional hazards model. RESULTS: The univariate hazard ratio (HR) for the development of DCI in patients who had lost consciousness for >1 hour was 6.0 (95% CI 3.0 to 12.0) compared with patients who had no loss or a <1-hour loss of consciousness. The presence of any risk factor for atherosclerosis yielded an HR of 1.4 (95% CI 0.6 to 3.5). The HR for unconsciousness remained essentially the same after adjustment for other risk factors for DCI. The HR for a poor World Federation of Neurological Surgeons score (grade IV or V) on admission was 2.9 (95% CI 1.5 to 5. 5); that for a large amount of subarachnoid blood on CT was 3.4 (95% CI 1.6 to 7.3). CONCLUSIONS: The duration of unconsciousness after subarachnoid hemorrhage is a strong predictor for the occurrence of DCI. This observation may contribute to a better understanding of the pathogenesis of DCI and increased attention for patients at risk.

Transient amnesia after perimesencephalic haemorrhage: the role of enlarged temporal horns.

OBJECTIVES: Although long term outcome of patients with perimesencephalic haemorrhage, a benign subset of subarachnoid haemorrhage, is excellent, some patients report an episode of amnesia for the first hours to days after the ictus. The relation between the occurrence of amnesia and the size of the ventricles on CT, including the temporal horns, were studied in patients with perimesencephalic haemorrhage. METHODS: Twenty seven consecutive patients with perimesencephalic haemorrhage were asked about the occurrence of amnesia. Age adjusted bicaudate indices and third ventricle sizes were calculated. Linear measurements of the temporal horn were taken in three directions: anterior-posterior, medial-lateral, and oblique. Additionally, enlargement of the temporal horns was assessed with the "naked eye". RESULTS: Ten of the 27 patients reported an episode of transient amnesia; in these patients the mean sizes of the temporal horns were larger than in patients without amnesia, ranging from a factor of 1.7 for the medial-lateral measurement to a factor of 2.3 for the anterior-posterior measurement. Most of the patients with amnesia had relative bicaudate indices and relative third ventricle sizes> 1, and all had enlarged temporal horns at "naked eye" assessment. CONCLUSION: About one third of patients with perimesencephalic haemorrhage have an episode of amnesia shortly after the bleed. The occurrence of amnesia is associated with enlargement of the temporal horns, and might be explained by temporary hippocampal dysfunction.

Quality of life in patients and partners after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Outcome after subarachnoid hemorrhage (SAH) is often graded as "poor," "fair," or "good." Such categories are usually based on physicians' assessments of physical abilities of patients rather than on how patients themselves perceive their physical, psychological, and social well-being. We assessed functional outcome and quality of life (QoL) in patients with SAH and their partners. METHODS: In a consecutive series of 64 patients and 51 partners studied 4 months after the SAH, we assessed functional outcome by means of the Rankin Scale, and QoL by means of the SF-36, the Sickness Impact Profile (SIP), and a visual analogue scale. Additionally, we asked two "simple questions" about dependency and recovery. All questionnaires were completed in an interview setting. The scores on the QoL instruments from patients and partners were stratified according to the Rankin grades of the patients and were compared with data from a Dutch reference population. RESULTS: Only patients who had no symptoms at all (Rankin grade 0) had no reduction in QoL compared with the reference population; some of these patients even indicated an improvement in QoL from before the SAH according to the visual analogue scale. Patients who had symptoms but were independent (Rankin grades 1 to 3) and therefore usually designated as having "good outcome" often had reductions in QoL, on both the physical and psychosocial subscores of the SIP and SF-36. The QoL of partners was considerably reduced in several psychosocial domains. CONCLUSIONS: SAH has a considerable impact on the QoL of patients and their partners. Only patients without residual symptoms (Rankin grade 0) have a good outcome in terms of physical performance and QoL.

Psychogenic pseudoptosis.

Three patients with psychogenic pseudoptosis of one eyelid are reported. All showed depression of the eyebrow on the affected side. The clinical course varied: in two patients the symptom resolved spontaneously after positive reassurance; in the third patient it remained unchanged for 2 years.

Quality of life after perimesencephalic haemorrhage.

Quality of life was measured by means of the sickness impact profile (SIP) questionnaire in a prospectively collected, consecutive series of 25 patients with perimesencephalic haemorrhage. A mean of two years and four months (range six months to six years) after the perimesencephalic haemorrhage, quality of life scores of the (former) patients were comparable with those of a random sample from the Dutch population. For physical aspects the patients showed even less dysfunction than controls. It is concluded that a perimesencephalic haemorrhage does not reduce quality of life or capacity to work.

Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review.

BACKGROUND: During the last three decades, new management strategies have been developed for patients with aneurysmal subarachnoid hemorrhage. To assess whether the case-fatality rate has improved after the introduction of new management strategies, we studied outcome in all population-based studies from 1960 onward. SUMMARY OF REVIEW: To identify population-based studies that reported on case-fatality rate in subarachnoid hemorrhage, we performed a MEDLINE search and checked all reference lists of the studies found. Two authors (J.W.H. and G.J.E.R.) independently assessed all studies for eligibility, using predefined criteria for case finding and diagnosis, and extracted data on case-fatality rates. We used weighted linear regression analysis to quantify change in case-fatality rate over time. We found 21 studies, describing 25 study periods between 1960 and 1992. Case-fatality rates varied between 32% and 67%, with the exception of one recent study. The case-fatality rate decreased by 0.5% per year (95% confidence interval, -0.1 to 1.2); the decline was steeper after adjustment for age and sex (0.9% per year; 95% confidence interval, -0.7 to 2.6; data from 12 studies). CONCLUSIONS: The case-fatality rate after subarachnoid hemorrhage has decreased during the last three decades. A plausible explanation for this decrease is the improved management of patients with subarachnoid hemorrhage.

[Attention in the medical curriculum for the sequelae of DES administration]. / Aandacht in het medisch curriculum voor de gevolgen van DES-gebruik.

There is still a lack of knowledge among physicians with respect to epidemiology, diagnosis, treatment and psychology of the former use of diethylstilboestrol (DES). A questionnaire was sent to 24 educational representatives of eight departments of general practice and 8 of gynaecology asking about the DES education programme in their departments. Response was 100%. Three of 8 general practice departments had a DES education programme, and all 8 gynaecology departments. With respect to epidemiology, diagnosis, treatment and psychology, the educational effort ranged from 50% to 75%, from 25% to 50%, and from 21% to 46% of the departments giving information regarding DES daughters, DES mothers, and DES sons respectively. The medical education with respect to DES depended much on the personal opinion and involvement of the individual teacher. Training of medical students with respect to the DES problem should be an integral part of preclinical medical education.