Impact of hyperleptinemia during placental ischemia-induced hypertension in pregnant rats.

The prevalence of preeclampsia and obesity have increased. Although obesity is a major risk factor for preeclampsia, the mechanisms linking these morbidities are poorly understood. Circulating leptin levels increase in proportion to fat mass. Infusion of this adipokine elicits hypertension in nonpregnant rats, but less is known about how hyperleptinemia impacts blood pressure during placental ischemia, an initiating event in the pathophysiology of hypertension in preeclampsia. We tested the hypothesis that hyperleptinemia during reduced uterine perfusion pressure (RUPP) exaggerates placental ischemia-induced hypertension. On gestational day (GD) 14, Sprague-Dawley rats were implanted with osmotic mini-pumps delivering recombinant rat leptin (1 µg/kg/min iv) or vehicle concurrently with the RUPP procedure to induce placental ischemia or Sham. On GD 19, plasma leptin was elevated in Sham + Leptin and RUPP + Leptin. Leptin infusion did not significantly impact mean arterial pressure (MAP) in Sham. MAP was increased in RUPP + Vehicle vs. Sham + Vehicle. In contrast to our hypothesis, placental ischemia-induced hypertension was attenuated by leptin infusion. To examine potential mechanisms for attenuation of RUPP-induced hypertension during hyperleptinemia, endothelial-dependent vasorelaxation to acetylcholine was similar between Sham and RUPP; however, endothelial-independent vasorelaxation to the nitric oxide (NO)-donor, sodium nitroprusside, was increased in Sham and RUPP. These findings suggest that NO/cyclic guanosine monophosphate (cGMP) signaling was increased in the presence of hyperleptinemia. Plasma cGMP was elevated in Sham and RUPP hyperleptinemic groups compared with vehicle groups but plasma and vascular NO metabolites were reduced. These data suggest that hyperleptinemia during placental ischemia attenuates hypertension by compensatory increases in NO/cGMP signaling.NEW & NOTEWORTHY Ours is the first study to examine the impact of hyperleptinemia on the development of placental ischemia-induced hypertension using an experimental animal model.

Does a regular Wessex Head Injury Matrix assessment identify early signs of infections in people with Prolonged Disorders of Consciousness?

BACKGROUND & OBJECTIVE: Patients with brain injury are at high risk for infections. Although infection and cognitive deterioration are established for people with dementia, this has not been shown for patients with a prolonged disorder of consciousness (PDOC). This study determines whether regular Wessex Head Injury Matrix (WHIM) assessments can identify early signs of infections in patients with PDOC. METHOD: Retrospective and prospective approaches were used to assess the WHIM scores of patients with a PDOC (N = 21 in the retrospective study and 22 in the prospective study). RESULTS: The WHIM total scores decreased due to infections in 17 of the 21 cases of infection (p < 0.001) in the retrospective study and 15 (p = 0.001) of the 22 prospective cases of infection. Patients in a minimally conscious state (MCS) showed a bigger proportion of change between their baseline score and the scores taken in the pre-infection stage in both the retrospective and prospective studies when compared to patients in a vegetative state (VS). CONCLUSION: The findings suggest the importance of serial WHIM assessments throughout the period of recovery, not only to measure cognitive changes but also to highlight underlying physical changes such as infections that will impact the response to rehabilitation and recovery.

Sheehan's syndrome and sickle cell disease: the story of Natasha.

Sheehan's syndrome (SS) is one of the pituitary disorders caused by severe blood loss during childbirth leading to necrosis of the pituitary gland. Diagnosis is made following severe haemorrhage, failure to produce milk and failure to menstruate. Rare in countries with good obstetric care, SS is still frequent in those countries with poor healthcare services. The majority of papers published on SS do not mention psychological or neuropsychological sequelae. Of those that do, mood disorders are sometimes reported and occasionally cognitive problems are noted, typically attention, memory or executive deficits. We report on Natasha, a British woman of Caribbean ancestry with sickle cell disease (SCD), diagnosed at age 33 years with SS following the birth of her second child. We know of no reports of a person with both SCD and SS. Natasha has been seen regularly for neuropsychological assessment and treatment for over two years. There has been a slight increase in her cognitive functioning but she remains with Balint's syndrome, so is unable to read. Treatment for this has been partially successful. Natasha presented with psychotic type symptoms when first seen but these have improved to a large extent. We believe that these symptoms are consistent with SS but the severe cognitive problems are more likely to be due to the strokes she suffered at the time of the haemorrhage and, possibly, to hypoxic damage caused by very low blood pressure.

TD: The case of Diogenes Syndrome-deficit or denial?

Diogenes Syndrome (DS) is characterised by extreme self-neglect, domestic squalor, hoarding, social withdrawal, and lack of concern and shame for the individual's residential situation. This paper describes TD who was unable to identify emotional expressions of disgust and was borderline-impaired for facial recognition associated with perceptual difficulties. Problems interpreting expressions of disgust were interesting as TD was living in squalor, neglecting himself, and lacked concern for his circumstances. This led us to question whether the basis of his difficulties were neuropsychological or psychological in nature, which became the objective of this study, with a focus on shame and disgust. TD completed neuropsychological and psychological assessments alongside an experimental task investigating processing of disgust and his living situation. Results highlighted executive dysfunction but understanding of living with the consequences of squalor was spared as was emotion based decision-making. Assessment indicated difficulties with olfactory processing and aspects of interoceptive awareness. TD showed poor awareness of his living conditions and a lack of shame. Disgust sensitivity was unimpaired. It is unclear if TD's difficulties were caused by psychological or neuropsychological impairments, although both likely play a part. Further research is required to understand processes underpinning DS, particularly disgust and shame.

Brugada syndrome and the story of Dave.

Brugada syndrome (BrS) is a little known genetic condition that causes severe disturbances in cardiac rhythm and may result in sudden unexpected cardiac death in an apparently healthy person. The heart structure is typically normal but there are problems with electrical activity. The syndrome is named after Spanish brothers who are cardiologists, Pedro and Josep Brugada. BrS is the major cause of sudden unexplained death syndrome (SUDS), also known as sudden arrhythmic death syndrome (SADS). Following a description of the syndrome, including its prevalence and incidence, how it is diagnosed and how it can be treated, we consider those who survive a cardiac arrest and what problems they may face. Most publications focus on the medical aspects of BrS but, of course, cardiac arrest can result in hypoxic brain damage. We conclude with the story of Dave, a 25-year-old man diagnosed with BrS following a nose bleed and subsequent cardiac arrest. He was left with a visual impairment, dystonia, hypersensitivity, and language and cognitive dysfunction. We look at Dave's strengths and weaknesses, his response to offered treatment, and his consequent improvement. We stress the contributions from members of the multidisciplinary team and offer suggestions for the rehabilitation of other survivors of BrS.

Akinetic mutism and the story of David.

Following a description about the characteristics of akinetic mutism (AM) and how it differs from locked-in syndrome (LIS) and a disorder of consciousness (DOC), we present the case of David, a 71-year-old man with AM. David sustained a stroke following a middle cerebral artery (MCA) thrombus. A CT scan at the time detected old ischaemic infarcts affecting the right frontal lobe, the left occipital lobe and the left parietal lobe so David had bilateral brain damage. Initially thought to have a DOC, further neuropsychological assessments administered when David had improved a little, resulted in the diagnosis of AM. Although David spoke little, when he did speak, his words and phrases were well articulated, grammatical and with appropriate intonation. He was alert and visually aware and he was not paralysed. We discuss whether the diagnosis was correct and address the difficulties in assessing such patients.

Alexander's disease and the story of Louise.

We describe the rare condition known as Alexander's disease or Alexander's leukodystrophy, which is essentially a childhood dementia. We then present the case of Louise Davies (we are using Louise's real name with the permission and special request of her mother), a woman who was diagnosed with this disease at the age of 5 years and is still alive at the age of 38, making her the longest known survivor of this condition. Although now severely impaired, both physically and mentally, and able to do very little, she has lived far longer than expected. We present some neuropsychological results from her childhood before measuring her decline over the past four years. We conclude by considering whether or not the diagnosis was correct and why she has lived so long.

The natural history of continuing improvement in an individual after a long period of impaired consciousness: The story of I.J.

AIM: Recovery of consciousness and recovery of function among patients with prolonged disorders of consciousness rarely occur. Those patients who do regain consciousness typically remain with severe disability. The aim of this retrospective study is to suggest that continuing improvement is possible in a survivor of catastrophic brain injury after being in a prolonged state of disordered consciousness. CASE STUDY: This retrospective single case study follows the progress of a 29 year old man, I.J, who sustained a severe traumatic brain injury following an assault in October 2011. He was in a vegetative state for 15 months and in a minimally conscious state for a further 4 months. This was followed by a slow and steady recovery of motor and cognitive functions. At 3 years post-injury I.J is considered to be moderately disabled. He is now living in the community with continuing outpatient support. On the disability rating scale his level of functioning is rated as mildly dependent. CONCLUSION: This study shows that continuing recovery to a level of moderate disability is possible, even after a prolonged disorder of consciousness. Intense multi-disciplinary long-term rehabilitation and cranioplasty may be contributing factors for such an unexpected recovery.

Comparison of neuropsychological rehabilitation techniques for unilateral neglect: an ABACADAEAF single-case experimental design.

Unilateral neglect is a debilitating attentional disorder whereby patients fail to report, respond or orient to information presented on one side of space. Previous studies have demonstrated improvements in neglect symptoms using rehabilitation techniques, such as anchoring or limb activation. We investigated the effectiveness of five interventions in reducing the unilateral neglect observed in patient F.P. A single-case ABACADAEAF design was used to investigate the effectiveness of musical stimulation (B), anchoring (C), vibratory stimulation (D), limb activation (E), and anchoring and vibratory stimulation combined (F), compared to baseline (A). Severity of neglect was measured using star cancellation, line crossing and line bisection tests. Tau-U statistical analyses were used to investigate significant differences between conditions. All interventions resulted in improvements in F.P.'s neglect. Anchoring (C), vibratory stimulation (D) and the combination of these two techniques (F) led to greatest improvements on all three tests of neglect. Musical stimulation led to improvements on the line bisection task only. Anchoring and vibratory stimulation were the most effective techniques for reducing neglect for this patient. Further research is needed to investigate whether the observed gains can be sustained on a longer-term basis, generalised to other tasks, and replicated in larger samples.

How do invasive predators and their native prey respond to prescribed fire?

Fire shapes animal communities by altering resource availability and species interactions, including between predators and prey. In Australia, there is particular concern that two highly damaging invasive predators, the feral cat (Felis catus) and European red fox (Vulpes vulpes), increase their activity in recently burnt areas and exert greater predation pressure on the native prey due to their increased exposure. We tested how prescribed fire occurrence and extent, along with fire history, vegetation, topography, and distance to anthropogenic features (towns and farms), affected the activity (detection frequency) of cats, foxes, and the native mammal community in south-eastern Australia. We used camera traps to quantify mammal activity before and after a prescribed burn and statistically tested how the fire interacted with these habitat variables to affect mammal activity. We found little evidence that the prescribed fire influenced the activity of cats and foxes and no evidence of an effect on kangaroo or small mammal (<800 g) activity. Medium-sized mammals (800-2000 g) were negatively associated with prescribed fire extent, suggesting that prescribed fire has a negative impact on these species in the short term. The lack of a clear activity increase from cats and foxes is likely a positive outcome from a fire management perspective. However, we highlight that their response is likely dependent upon factors like fire size, severity, and prey availability. Future experiments should incorporate GPS-trackers to record fine-scale movements of cats and foxes in temperate ecosystems immediately before and after prescribed fire to best inform management within protected areas.

AwareCare: a pilot randomized controlled trial of an awareness-based staff training intervention to improve quality of life for residents with severe dementia in long-term care settings.

BACKGROUND: The extent to which care home residents with severe dementia show awareness is influenced by the extent to which the environment provides opportunities for engagement and by the way in which care staff interact with them. We aimed to establish whether training care staff to observe and identify signs of awareness in residents with severe dementia resulted in improved quality of life for residents. METHODS: In this pilot cluster randomized trial, care staff in four homes (n = 32) received training and supervision and carried out structured observations of residents using the AwareCare measure (n = 32) over an eight-week period, while staff in four control homes (n = 33) had no training with regard to their residents (n = 33) and no contact with the research team. The primary outcome was resident quality of life. Secondary outcomes were resident well-being, behavior and cognition, staff attitudes and well-being, and care practices in the home. RESULTS: Following intervention, residents in the intervention group had significantly better quality of life as rated by family members than those in the control group, but care staff ratings of quality of life did not differ. There were no other significant between-group differences. Staff participating in the intervention identified benefits in terms of their understanding of residents' needs. CONCLUSIONS: Staff were able to use the observational measure effectively and relatives of residents in the intervention homes perceived an improvement in their quality of life.

Paradoxical improvement of function more than 2 years after onset of tuberculous meningitis.

OBJECTIVE: To document the unexpected improvement made by a 50 year-old patient over 2 years after being diagnosed with tuberculous meningitis (TBM). METHODS: Regular neuropsychological assessments were carried out, initially with a test for patients in reduced states of awareness and later with more demanding tests. RESULTS: The patient was diagnosed with TBM in November 2008 and was mute, stuporous and barely more than minimally conscious for over 2 years. By February 2011, following the cessation of TBM medication, her conscious level had improved and she could be assessed on a range of neuropsychological tests. The patient presented with diffuse cognitive impairments coupled with focal neurological signs, but showed marked improvements in cognitive functioning compared to when admitted. CONCLUSIONS: This study demonstrates that late stage neuropsychological improvement is possible, even after 2 years of showing minimal awareness. Such paradoxical improvement of function is considered in the light of other paradoxical phenomena in TBM, comparisons are offered with similar neurological conditions and possible mechanisms underlying the dramatic improvement that took place are suggested.

Assessment of nondeclarative learning in severe Alzheimer dementia: the Implicit Memory Test (IMT).

Although patients with Alzheimer dementia (AD) have impaired explicit memory, more automatic, implicit aspects of learning and memory may be relatively preserved. However, neuropsychological tests for the assessment of implicit memory are lacking. This study examines a newly developed test, the Implicit Memory Test, in 28 patients with severe AD (mini-mental state examination 5 to 12) and 22 cognitively unimpaired matched controls (mini-mental state examination 25 to 29). The Implicit Memory Test consists of visually presented word (stem-completion) and picture (fragmented picture identification) subtests, each comprising 3 learning trials and a delayed test. Explicit memory was also assessed, using the verbal paired-associate learning subtest from the Wechsler Memory Scale and the Visual Association Test. Patients with AD obtained a floor performance on both explicit memory tests, whereas a significant learning curve was found for both the stem-completion and the fragmented pictures subtests of the Implicit Memory Test. Delayed testing on the fragmented pictures subtest showed a preserved performance that may have been mediated by implicit learning. Delayed performance on the stem-completion subtest, however, showed clear memory decay that suggests contamination by explicit memory function, at least in the controls. These findings extend the earlier results on word-stem completion and fragmented picture identification in patients with mild-to-moderate AD and indicate that residual learning capacity can be assessed in severe AD.

A case study of locked-in-syndrome: psychological and personal perspectives.

OBJECTIVES: Although patients with Locked-In-Syndrome (LIS) are often stated to have normal cognitive functioning, the few reports of neuropsychological assessment in these cases suggest this is not always true. This paper (a) reviews published reports of neuropsychological assessments of LIS patients, (b) presents a detailed neuropsychological assessment of a patient to determine if she has normal cognitive functioning and (c) presents the views of the patient on what has happened to her. METHODS AND PROCEDURES: An in-depth single case report assessing the cognitive and emotional functioning of a young woman with LIS plus a personal account from the patient. Detailed assessments were carried out using standardized neuropsychological tests and questionnaires measuring emotional functioning, pain and quality-of-life. The patient also states her views of what happened and how she feels. RESULTS: On most tests, cognitive functioning was average or above, but some impairments were found (consistent with published literature). No emotional problems were detected. Quality of life was satisfactory. Pain perception was normal. CONCLUSIONS: Although LIS patients have no severe cognitive deficits, some cognitive difficulties are common. Despite severe physical and communication problems and some mild cognitive deficits on visual reasoning tasks, this patient feels she has a reasonable quality-of-life.