Recurrent stroke/TIA in cryptogenic stroke patients with patent foramen ovale

BACKGROUND: Patent foramen ovale (PFO) is present in 40% of patients with cryptogenic stroke and may be associated with paradoxical emboli to the brain. Therapeutic options include antiplatelet agents, anticoagulation, percutaneous device and surgical closure. We assessed the hypothesis that there are differences in rates of recurrent TIA or stroke between patients in the four treatment groups. METHODS: Patients presenting from January 1997 with cryptogenic stroke or TIA and PFO were followed prospectively until June 2003. Treatment choice was made on an individual case basis. The primary outcome was recurrent stroke. The secondary outcome was a composite of stroke, TIA, and vascular death. RESULTS: Baseline. Our cohort consisted of 121 patients; 64 (53%) were men. Median age was 43 years. Sixty-nine percent presented with stroke and 31% with TIA. One or more vascular risk factor was present in 40%. Atrial septal aneurysm (ASA) was present in 24%. Treatment consisted of antiplatelet agents (34%), anticoagulation (17%), device (39%) and surgical closure (11%). Follow-up. Recurrent events occurred in 16 patients (9 antiplatelet, 3 anticoagulation, 4 device closure); 7 were strokes, 9 were TIA. Comparing individual treatments there was a trend toward more strokes in the antiplatelet arm (p = 0.072); a significant difference was seen for the composite endpoint (p = 0.012). Comparing closure versus combined medical therapy groups, a significant difference was seen for primary (p = 0.014) and secondary (p = 0.008) outcomes, favoring closure. Age and pre-study event predicted outcome. CONCLUSION: Patent foramen ovale closure was associated with fewer recurrent events. Complications of surgical and device closure were self-limited.     

Clinimetric properties of participation measures for 5- to 13-year-old children with cerebral palsy: a systematic review

This study systematically reviewed the validity, reliability, sensitivity to change, and clinical utility of measurements of participation for children with cerebral palsy. Sixteen measures were identified and seven met the inclusion criteria of having 30% content measuring participation, for use with children aged 5 to 13 years with physical disability, and were condition specific. The Children's Assessment of Participation and Enjoyment (CAPE) assessed participation in leisure and recreation, while the School Function Assessment (SFA) and School Outcome Measure addressed participation in the school environment. The Assessment of Life Habits for Children (LIFE-H) measured participation in home, school, and community life, and the Children Helping Out: Responsibilities and Expectations assessed children's participation in household duties. The Canadian Occupational Performance Measure (COPM) and Goal Attainment Scaling (GAS) were individualized tools used to evaluate goal achievement. Results showed most instruments had adequate reliability and validity. The COPM and GAS were the only measures that reported adequate responsiveness to detect clinically significant change. Limited data are currently available to determine the responsiveness of the CAPE, LIFE-H, and SFA. A combination of assessments is required to capture participation of children in home, school, and community environments.     

Neural biases to covert and overt signals of fear: dissociation by trait anxiety and depression

Although biases toward signals of fear may be an evolutionary adaptation necessary for survival, heightened biases may be maladaptive and associated with anxiety or depression. In this study, event-related potentials (ERPs) were used to examine the time course of neural responses to facial fear stimuli (versus neutral) presented overtly (for 500 msec with conscious attention) and covertly (for 10 msec with immediate masking to preclude conscious awareness) in 257 nonclinical subjects. We also examined the impact of trait anxiety and depression, assessed using psychometric ratings, on the time course of ERPs. In the total subject group, controlled biases to overtly processed fear were reflected in an enhancement of ERPs associated with structural encoding (120-220 msec) and sustained evaluation persisting from 250 msec and beyond, following a temporo-occipital to frontal topography. By contrast, covert fear processing elicited automatic biases, reflected in an enhancement of ERPs prior to structural encoding (80-180 msec) and again in the period associated with automatic orienting and emotion encoding (230-330 msec), which followed the reverse frontal to temporo-occipital topography. Higher levels of trait anxiety (in the clinical range) were distinguished by a heightened bias to covert fear (speeding of early ERPs), compared to higher depression which was associated with an opposing bias to overt fear (slowing of later ERPs). Anxiety also heightened early responses to covert fear, and depression to overt fear, with subsequent deficits in emotion encoding in each case. These findings are consistent with neural biases to signals of fear which operate automatically and during controlled processing, feasibly supported by parallel networks. Heightened automatic biases in anxiety may contribute to a cycle of hypervigilance and anxious thoughts, whereas depression may represent a "burnt out" emotional state in which evaluation of fear stimuli is prolonged only when conscious attention is allocated.     

Functional disconnections in the direct and indirect amygdala pathways for fear processing in schizophrenia

BACKGROUND: Schizophrenia patients show reduced neural activity, relative to controls, in the amygdala and its projection to the medial prefrontal cortex (MPFC) in response to fear perception. In this study we tested the hypothesis that schizophrenia is characterized by abnormal functional connectivity in the amygdala network underlying fear perception. METHODS: Functional MRI images were acquired from 14 schizophrenia patients and 14 matched healthy control subjects during an emotion perception task, in which fearful and neutral facial expression stimuli were presented pseudorandomly under nonconscious (using masking) and conscious conditions. Both subtraction and functional connectivity analyses were undertaken using a region of interest approach. RESULTS: In response to fearful facial expressions, schizophrenia patients displayed reduced amygdala activity, compared to controls, in both the conscious and nonconscious conditions. The amygdala displayed a reversal of the normal pattern of connectivity with the brainstem, visual cortex, and also with the dorsal and ventral divisions of the MPFC in the schizophrenia patients. CONCLUSIONS: The presence of functional disconnections in amygdala pathways suggests that schizophrenia patients have a failure in coordinating their automatic orienting to salient signals and the associated prefrontal monitoring of these signals.     

Mapping frontal-limbic correlates of orienting to change detection

Orienting responses are elicited by salient stimuli, and may be indexed by skin conductance responses. Concurrent functional magnetic resonance imaging and skin conductance response recording was used to identify neural correlates of orienting to abrupt sensory change (infrequent high pitch oddball 'target' tones embedded in frequent lower pitch 'standard' tones) in 16 healthy participants. 'With skin conductance response' responses to targets were distinguished by preferentially greater activity in the amygdala and ventral medial and lateral frontal cortical regions. By contrast, 'without skin conductance response' responses elicited distinctive activity in the dorsal lateral frontal cortex and supramarginal gyrus. These findings suggest that orienting to unexpected sensory change elicits a network for appraising salience and novelty, whereas, in the absence of orienting, a parallel network for sensory and context evaluation is preferentially engaged.     

Brain maturation in adolescence: concurrent changes in neuroanatomy and neurophysiology

Adolescence to early adulthood is a period of dramatic transformation in the healthy human brain. However, the relationship between the concurrent structural and functional changes remains unclear. We investigated the impact of age on both neuroanatomy and neurophysiology in the same healthy subjects (n = 138) aged 10 to 30 years using magnetic resonance imaging (MRI) and resting electroencephalography (EEG) recordings. MRI data were segmented into gray and white matter images and parcellated into large-scale regions of interest. Absolute EEG power was quantified for each lobe for the slow-wave, alpha and beta frequency bands. Gray matter volume was found to decrease across the age bracket in the frontal and parietal cortices, with the greatest change occurring in adolescence. EEG activity, particularly in the slow-wave band, showed a similar curvilinear decline to gray matter volume in corresponding cortical regions. An inverse pattern of curvilinearly increasing white matter volume was observed in the parietal lobe. We suggest that the reduction in gray matter primarily reflects a reduction of neuropil, and that the corresponding elimination of active synapses is responsible for the observed reduction in EEG power.     

General and social cognition in first episode schizophrenia: identification of separable factors and prediction of functional outcome using the IntegNeuro test battery

OBJECTIVE: It is increasingly recognized that cognitive assessments, unlike symptom ratings, provide a reliable predictor of functional outcome in schizophrenia. This study evaluated the utility of the 'IntegNeuro' computerized test battery for assessing cognition in first episode schizophrenia. We determined the presence of separable factors of general and social cognition, their equivalence to the consensus domains identified by the NIMH MATRICS project, and their effectiveness in predicting real world functional outcomes. METHOD: Fifty six first episode schizophrenia (FES) patients and 112 matched healthy controls were assessed on the touchscreen-based 'IntegNeuro' cognitive test battery and FES patients for social functioning (SOFAS) and quality of life (WHOQOL-BREF). RESULTS: Principal components analysis identified i) six factors corresponding to MATRICS domains of general cognition ('Information Processing Speed', 'Verbal Recall', 'Working Memory Capacity', 'Sustained Attention/Vigilance', 'Verbal Processing', 'Executive Function'), ii) an 'Emotional Intelligence' factor corresponding to the MATRICS social cognition domain, and iii) an additional 'Sensori-Motor Function' factor of general cognition and 'Negativity' factor of social cognition. Patients showed impairments relative to controls across all factors, but especially for Working Memory Capacity, followed by Verbal Memory, Sustained Attention/Vigilance and Negativity. These factors strongly predicted poorer social functioning in FES, along with poorer quality of life in psychological, social, and health satisfaction facets. CONCLUSION: The IntegNeuro battery has utility for assessing separable domains of general and social cognition in FES, which are predictive of real world outcomes. Thus, it may be appropriate for clinical application, including in multi-center trials targeting new treatments for cognition in schizophrenia.     

Advanced nursing practice in paediatric critical care

Following the successful implementation of High Dependency Care: a model for development at King's College hospital in 2005, the authors wished to consider the addition of a fourth tier to the model. A review of the clinical environment was undertaken and it was suggested that the introduction of an advanced nurse practitioner could contribute to the education and continuation of the outreach service detailed in the model, as well as to the improvement of critical care services and career development opportunities for nurses within the unit. A survey was undertaken to identify the views of medical and nursing staff about essential roles and responsibilities of advanced nurse practitioners in this area. This would then direct the development of a teaching and competency programme that could promote advanced practice in the critical care environment. There was no consensus on the tasks advanced nurse practitioners can undertake, the appropriate mentors in the clinical environment, the level of education they must achieve, nor the time in which this should be completed. There was confusion about the qualifications required for advanced nursing practice, mentorship and training. However, there was support for this role and respondents confirmed the view that advanced nursing practiced would be beneficial in patient care delivery.