Neural Correlates of Impaired Self-awareness of Deficits after Acquired Brain Injury: A Systematic Review.

Self-awareness is essential for the process and outcome of rehabilitation but is often affected by acquired brain injury (ABI). While many studies investigated the psychological aspects of self-awareness deficits, the biological underpinnings are not well understood. The aim of this systematic review was to identify the neural correlates of self-awareness after ABI. Results indicate that anticipation of future problems is associated with lesions and decreased neural functioning in the right frontal lobe, as well as increased diffusivity throughout the white matter of the brain. Poor behavioral adjustment on implicit awareness tasks is associated with less functional connectivity of anterior cingulate cortex and right or middle inferior frontal gyri to the fronto-parietal control network, as well as more activation in the left insula and left parietal operculum during error processing. Recognition of mistakes is associated with internetwork connectivity of anterior or posterior default mode network to salience network. In conclusion, after ABI, different results in brain activation and connectivity are found depending on level of awareness measured. Future studies are necessary to confirm these findings.

Detecting and treating the protean manifestations of diabetic autonomic neuropathy.

The manifestations of diabetic autonomic neuropathy (DAN) are protean and clinically involve multiple systems, including the cardiovascular system, the gastrointestinal system, the genitourinary system as well as the sweat glands (sudomotor dysfunction) and the gallbladder. In addition, cardiac autonomic neuropathy (CAN) is associated with a correctible inability to appreciate and correct hypoglycaemia. While not a clinical problem, pupillary involvement should be the clue and the catalyst to investigate for other manifestations of DAN. This review outlines a practical approach to detecting and investigating the manifestations of DAN. Of particular importance is early detection of cardiovascular involvement where prompt therapy through glycaemic control can decrease the severity of CAN and decelerate the frequency and severity of retinopathy and nephropathy in addition to decreasing cardiovascular events and mortality. CAN also plays a role in accelerating other diabetic complications such as acute ischaemic stroke, heart failure, medial artery calcinosis, foot ulcers, peripheral artery disease and Charcot joints. Many therapies of DAN are available, which should not only decrease morbidity and mortality from DAN, but also improve the patient's quality of life. However, the therapies available are largely symptomatic.

The study of healthcare facility utilization problems faced by pregnant women in urban north India.

OBJECTIVES: Sub-Saharan African countries account for nearly half of maternal deaths, and Southern Asian countries are second in the 85% of deaths that occur worldwide. Despite this fact, there is a rapid enhancement in the number of skilled health workers. There has been a sharp increase of 53% in 1990 and 61% in 2007 in trained birth attendant utilization shows that attention is being paid to the management of labor services. But surprisingly, still, the births take place without the assistance of trained health personnel in Southern Asian countries and Sub-Saharan Africa. The objective of this study is the assessment of barriers to health care facility utilization and its management concerning labor problems in urban North India. METHODS: A sample of "300" pregnant urban women was taken for study and analysis. A convenience sampling method was used. The factor analysis was applied for the interpretation and analysis of the data. RESULTS: It was found that there were inadequacies in services as well as unawareness of services in almost all urban areas among pregnant women. CONCLUSIONS: The tremendous increase in the cost of services and corrupt behavior among the service providers rampantly found in the urban locations, inaccessibility of proper means of communication and also economic backwardness and low literacy became the impediment to the utilization of maternal healthcare services in North-India.

Sleep deprivation prevents counterregulatory adaptation to recurrent hypoglycaemia.

AIMS/HYPOTHESIS: Attenuated counterregulation after recurrent hypoglycaemia is a major complication of diabetes treatment. As there is previous evidence for the relevance of sleep in metabolic control, we assessed the acute contribution of sleep to the counterregulatory adaptation to recurrent hypoglycaemia. METHODS: Within a balanced crossover design, 15 healthy, normal-weight male participants aged 18-35 years underwent three hyperinsulinaemic-hypoglycaemic clamps with a glucose nadir of 2.5 mmol/l, under two experimental conditions, sleep and sleep deprivation. Participants were exposed to two hypoglycaemic episodes, followed by a third hypoglycaemic clamp after one night of regular 8 h sleep vs sleep deprivation. The counterregulatory response of relevant hormones (glucagon, growth hormone [GH], ACTH, cortisol, adrenaline [epinephrine] and noradrenaline [norepinephrine]) was measured, and autonomic and neuroglycopenic symptoms were assessed. RESULTS: Sleep deprivation compared with sleep dampened the adaptation to recurrent hypoglycaemia for adrenaline (p=0.004), and this pattern also emerged in an overall analysis including adrenaline, GH and glucagon (p=0.064). After regular sleep, the counterregulatory responses of adrenaline (p=0.005), GH (p=0.029) and glucagon (p=0.009) were attenuated during the 3rd clamp compared with the 1st clamp, but were preserved after sleep deprivation (all p>0.225). Neuroglycopenic and autonomic symptoms during the 3rd clamp compared with the 1st clamp were likewise reduced after sleep (p=0.005 and p=0.019, respectively). In sleep deprivation, neuroglycopenic symptoms increased (p=0.014) and autonomic symptoms were unchanged (p=0.859). CONCLUSIONS/INTERPRETATION: The counterregulatory adaptation to recurrent hypoglycaemia is compromised by sleep deprivation between hypoglycaemic episodes, indicating that sleep is essential for the formation of a neurometabolic memory, and may be a potential target of interventions to treat hypoglycaemia unawareness syndrome.

Finding Eden - alternative transplantation sites for pancreatic islets.

Pancreatic islets transplantation is an established treatment method for type 1 diabetic patients with the hypoglycemia unawareness syndrome in whom a therapy with modern technologies fails. Islet transplantation is most commonly done using an interventional radiology method: a tissue suspension of pancreatic islets is applied into a branch of the portal vein through a percutaneously installed catheter. Although being minimally invasive unlike pancreas organ transplant, this method is associated with many technical difficulties. Possible complications of the procedure include hemorrhage and portal vein thrombosis. Unlike their natural dispersed localization in exocrine pancreas, isolated pancreatic islets are exposed to hypoxia, toxins and immunosuppressive drugs in the liver parenchyma. Direct contact with the recipients blood causes an instant blood mediated inflammatory reaction (IBMIR) resulting in the death of more than half of the pancreatic islets shortly after their application. Therefore the size of the islet graft is often insufficient and a number of transplanted patients require administration of exogenous insulin. All of these are reasons for seeking an alternative transplantation site with more hospitable conditions for long-term islet survival. Various transplantation sites have been tested in experimental and clinical research. The advantages and disadvantages of some of them are summarized in this paper. Currently, transplantation into the greater omentum seems most promising, which has already been used in clinical practice at several institutions.

Transplant Options for Patients With Diabetes and Advanced Kidney Disease: A Review.

Optimal glycemic control in kidney transplant recipients with diabetes is associated with improved morbidity and better patient and allograft survival. Transplant options for patients with diabetes requiring insulin therapy and chronic kidney disease who are suitable candidates for kidney transplantation should include consideration of ß-cell replacement therapy: pancreas or islet transplantation. International variation related to national regulatory policies exists in offering one or both options to suitable candidates and is further affected by pancreas/islet allocation policies and transplant waiting list dynamics. The selection of appropriate candidates depends on patient age, coexistent morbidities, the timing of referral to the transplant center (predialysis versus on dialysis) and availability of living kidney donors. Therefore, early referral (estimated glomerular filtration rate < 30 mL/min/1.73 m2) is of the utmost importance to ensure adequate time for informed decision making and thorough pretransplant evaluation. Obesity, cardiovascular disease, peripheral vascular disease, smoking, and frailty are some of the conditions that need to be addressed before acceptance on the transplant list, and ideally before dialysis becoming imminent. This review offers insights into selection of pancreas/islet transplant candidates by transplant centers and an update on posttransplant outcomes, which may have practice implications for referring nephrologists.

Patients with highly unstable type 1 diabetes eligible for islet transplantation can be managed with a closed-loop insulin delivery system: A series of N-of-1 randomized controlled trials.

AIM: To compare the efficacy of the closed-loop Diabeloop for highly unstable diabetes (DBLHU) system with the open-loop predictive low glucose suspend (PLGS) system in patients with highly unstable type 1 diabetes (T1D) who experience acute metabolic events. METHODS: DBLHU-WP10 was an interventional, controlled, randomized, open-label study that comprised two cycles of N-of-1 trials (2-of-1 trials). Each trial consisted of two crossover 4-week periods of treatment with either DBLHU or PLGS in randomized order. The primary outcome was the percentage of time spent in the 70-180 mg/dL glucose range (time in range [TIR]). RESULTS: Five out of seven randomized patients completed the aggregated 2-of-1 trials. TIR was significantly higher with DBLHU (73.3% ± 1.7%) compared with PLGS (43.5% ± 1.7%; P < .0001). The percentage of time below 70 mg/dL was significantly lower with DBLHU (0.9% ± 0.4%) versus PLGS (3.7% ± 0.4%; P < .0001). DBLHU was also significantly superior to PLGS in reducing hyperglycaemic excursions and improving almost all other secondary outcomes, including glucose variability and satisfaction score. No adverse event could be related to the experimental treatment. CONCLUSIONS: DBLHU was superior to PLGS in improving the metabolic control of patients with highly unstable T1D who require an islet or pancreas transplant but who either have a contraindication or refuse to consent.

The relations between cognitive and motivational components of anosognosia for left-sided hemiplegia and the right hemisphere dominance for emotions: A historical survey.

Since the description of anosognosia for hemiplegia by Babinski (who also stressed the links between anosognosia and right hemisphere damage) both motivational and cognitive mechanisms have been advanced to explain this awareness disorder. In this review I will discuss first the neurophysiological mechanisms that can impede the discovery of the motor deficits contralateral to the brain lesion and then suggest that some instances of anosognosia for left-sided hemiplegia may also be due to motivational mechanisms of denial. Among the cognitive mechanisms, sensory feedback and intentional feed-forward disorders can lead to a poor awareness of the motor defects, whereas denial mechanisms could result from an interaction between the right hemisphere dominance for emotions and the anxiety raised by the catastrophic consequences of the brain damage. In particular, a maladaptive reaction to the personal implications of the brain lesion could be revealed by the presence of an implicit acknowledgement of the motor defect.

Hypoglycaemia and its management in primary care setting.

Hypoglycaemia is common in patients with type 1 diabetes and type 2 diabetes and constitutes a major limiting factor in achieving glycaemic control among people with diabetes. While hypoglycaemia is defined as a blood glucose level under 70 mg/dL (3.9 mmol/L), symptoms may occur at higher blood glucose levels in individuals with poor glycaemic control. Severe hypoglycaemia is defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions to assure neurologic recovery. Hypoglycaemia is the most important safety outcome in clinical studies of glucose lowering agents. The American Diabetes Association Standards of Medical Care recommends that a management protocol for hypoglycaemia should be designed and implemented by every hospital, along with a clear prevention and treatment plan. A tailored approach, using clinical and pathophysiologic disease stratification, can help individualize glycaemic goals and promote new therapies to improve quality of life of patients. Data from recent large clinical trials reported low risk of hypoglycaemic events with the use of newer anti-diabetic drugs. Increased hypoglycaemia risk is observed with the use of insulin and/or sulphonylureas. Vulnerable patients with T2D at dual risk of severe hypoglycaemia and cardiovascular outcomes show features of "frailty." Many of such patients may be better treated by the use of GLP-1 receptor agonists or SGLT2 inhibitors rather than insulin. Continuous glucose monitoring (CGM) should be considered for all individuals with increased risk for hypoglycaemia, impaired hypoglycaemia awareness, frequent nocturnal hypoglycaemia and with history of severe hypoglycaemia. Patients with impaired awareness of hypoglycaemia benefit from real-time CGM. The diabetes educator is an invaluable resource and can devote the time needed to thoroughly educate the individual to reduce the risk of hypoglycaemia and integrate the information within the entire construct of diabetes self-management. Conversations about hypoglycaemia facilitated by a healthcare professional may reduce the burden and fear of hypoglycaemia among patients with diabetes and their family members. Optimizing insulin doses and carbohydrate intake, in addition to a short warm up before or after the physical activity sessions may help avoiding hypoglycaemia. Several therapeutic considerations are important to reduce hypoglycaemia risk during pregnancy including administration of rapid-acting insulin analogues rather than human insulin, pre-conception initiation of insulin analogues, and immediate postpartum insulin dose reduction.

The principle of distance during COVID-19 outbreak in Korea.

The majority of confirmed COVID-19 cases in Korea have been related to mass infection. The nation must urgently promote the distance awareness approach during emergency response and discourage the distance unawareness approach. Other nations may also apply the principle of distance to their pandemic management.

Memory impairment and Alzheimer's disease pathology in individuals with MCI who underestimate or overestimate their decline.

OBJECTIVES: The aim of this study was to examine whether the discrepancy between participant and informant estimation of memory decline can predict MCI prognosis. METHODS: Analyses involved data from individuals with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who filled the Everyday Cognition questionnaire. Participants who underestimated (N = 112) and overestimated (N = 157) their memory decline were compared on memory tasks, brain volume, and cerebrospinal markers, at study entry and after 24 months. RESULTS: Individuals who underestimated their memory decline performed more poorly on memory tests, had smaller hippocampus volume, and greater Alzheimer's disease pathology than did individuals who overestimated their cognitive decline. Longitudinal comparisons demonstrated that individuals who underestimated their decline deteriorated more significantly in memory and in brain measures. CONCLUSIONS: Underestimation of memory decline should raise clinicians' suspicion of the existence of AD pathology in individuals with MCI.

Factory-calibrated continuous glucose monitoring and capillary blood glucose monitoring in a case with insulinoma: usefulness and possible pitfall under chronic hyperinsulinemic hypoglycemia.

The accuracy of factory-calibrated continuous glucose monitoring (fCGM) within hypoglycemic ranges, especially under the status of chronic hyperinsulinemic hypoglycemia like insulinomas, remains an issue. Even so, fCGM is known to be useful for detecting hypoglycemia unawareness in insulinoma cases. A 25-year-old woman presenting with sudden unconsciousness was diagnosed with insulinoma; fCGM facilitated diagnosis by continuous monitoring for hypoglycemia. Before surgery, she was treated with continuous and frequent bolus infusions of 50% glucose via central venous catheter. To evaluate the accuracy of fCGM values in this case, a comparison between fCGM and capillary blood glucose (CBG) values was also performed. According to the simultaneously measured values, those of fCGM were largely in accordance with those of CBG. Moreover, compared with the previously reported case not having glucose infusions via central venous catheter, both the mean absolute relative differences (MARDs) and the absolute differences (Δ glucose) between fCGM and CBG values were larger in the present case, although no significant differences of MARDs and Δ glucose between the two cases were observed in several different conditions including fasting, post-meal, hypoglycemia, and others. Therefore, we should note possible increased differences between fCGM and CBG values in cases using frequent intravenous glucose infusions as well as case-dependent differing levels of consistency between them.

Consciousness recovery after various periods in vegetative state.

BACKGROUND: Recent studies suggest that late recovery from vegetative state (VS) is more prevalent today than previously thought. This study examined the decline in the rate of recovery from VS with time after admission to rehabilitation, and established a new time frame, in which the odds of recovery from VS remain substantial. METHODS: Data of 206 patients with VS after traumatic and non-traumatic brain injuries (TBI and NTBI), who were treated at the Loewenstein Rehabilitation Hospital (LRH), in Raanana, Israel, between 2003 and 2015, and described in a previous publication, were further analysed. Rate of recovery from VS was monitored at several time points after admission to intensive care and consciousness rehabilitation (ICCR). RESULTS: The odds of consciousness recovery were at least 54% at admission to ICCR, and 48%, 33%, 19%, and 7% at 3, 6, 9, and 12 months after admission, respectively. CONCLUSIONS: The rate of recovery from VS decreases significantly with time, but contrary to previous consensus, 6-12 months after admission to ICCR, the odds of recovery from VS after TBI and NTBI remain substantial.

Dissociation in awareness of memory and language decline in Alzheimer's disease.

OBJECTIVES: The aim of this study was to examine awareness of decline in memory and in language in individuals with Alzheimer's disease (AD), by comparing participant and informant ratings, as well as these ratings and actual test performance. METHODS: We analyzed data from 149 individuals with AD enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who filled the Everyday Cognition questionnaire and performed memory and language tasks. RESULTS: Participants provided significantly lower assessments of decline than did informants for both memory and language. There was a negative association between informant ratings and memory test scores but no association between participant ratings and memory test scores. Both participant and informant ratings correlated negatively with performance on the language tests. Informant, but not participant, ratings contributed to the prediction of one memory variable beyond demographic factors. Participant ratings contributed to the prediction of language scores beyond demographic factors more than did informant ratings. CONCLUSIONS: The findings reflect better awareness of decline in language than of decline in memory in individuals with AD.

Interaction between memory impairment and depressive symptoms can exacerbate anosognosia: a comparison of Alzheimer's disease with mild cognitive impairment.

OBJECTIVE: To investigate the effects of interactions between memory impairment, depressive symptoms, and anosognosia. METHODS: Anosognosia for memory impairment was assessed in 118 patients with Alzheimer's disease (AD), 47 patients with mild cognitive impairment (MCI), and 17 non-diagnosed controls (NC) using a questionnaire and evaluation of the anosognosia score as the discrepancy between ratings of the patient and a relative. Demographic characteristics, such as the relationship of the patient with the relative and the activities of daily living (ADL) were evaluated. Memory impairment was evaluated with the Rivermead Behavioral Memory Test (RBMT), depressive symptoms were evaluated using the Geriatric Depression Scale (GDS) 15 items version. RESULTS: In the MCI group, a stepwise multiple regression analysis showed an interaction between RBMT and GDS scores, and simple slope analysis indicated that scores for RBMT at low GDS (-1 standard deviation) were positively correlated with self-rated memory impairment. In the AD group, the relationship of the patient with the relative, ADL, and GDS and RBMT scores were associated with the anosognosia score. CONCLUSION: Patients with MCI who have no depressive symptoms may be able to more accurately evaluate their memory impairment than those who have depressive symptoms and patients with AD. The evaluation by relatives, depressive symptoms or ADL of patients may distort evaluation of anosognosia for memory impairment in patients with AD or MCI. It seems necessary to include not only depression scale scores but also results of objective memory tests in the patients' medical information for the correct assessment of anosognosia.

Interdisciplinary approach to compensation of hypoglycemia in diabetic patients with chronic heart failure.

Diabetes mellitus is a chronic disease requiring lifelong control with hypoglycemic agents that must demonstrate excellent efficacy and safety profiles. In patients taking glucose-lowering drugs, hypoglycemia is a common cause of death associated with arrhythmias, increased thrombus formation, and specific effects of catecholamines due to sympathoadrenal activation. Focus is now shifting from merely glycemic control to multifactorial approach. In the context of individual drugs and classes, this article reviews interdisciplinary strategies evaluating metabolic effects of drugs for treatment of chronic heart failure (CHF) which can mask characteristic hypoglycemia symptoms. Hypoglycemia unawareness and cardiac autonomic neuropathy are discussed. Data suggesting that hypoglycemia modulates immune response are reviewed. The potential role of gut microbiota in improving health of patients with diabetes and CHF is emphasized. Reports stating that nondiabetic CHF patients can have life-threatening hypoglycemia associated with imbalance of thyroid hormones are discussed. Regular glycemic control based on HbA1c measurements and adequate pharmacotherapy remain the priorities in diabetes management. New antihyperglycemic drugs with safer profiles should be preferred in vulnerable CHF patients. Multidrug interactions must be considered. Emerging therapies with reduced hypoglycemia risk, telemedicine, sensor technologies, and genetic testing predicting hypoglycemia risk may help solving the challenges of hypoglycemia in CHF patients with diabetes. Interdisciplinary work may involve cardiologists, diabetologists/endocrinologists, immunologists, gastroenterologists, microbiologists, nutritionists, imaging specialists, geneticists, telemedicine experts, and other relevant specialists. This review emphasizes that systematic knowledge on pathophysiology of hypoglycemia in diabetic patients with CHF is largely lacking and the gaps in our understanding require further discoveries.

Prevention and Management of Severe Hypoglycemia and Hypoglycemia Unawareness: Incorporating Sensor Technology.

PURPOSE OF REVIEW: In addition to assisting in achieving improved glucose control, continuous glucose monitoring (CGM) sensor technology may also aid in detection and prevention of hypoglycemia. In this paper, we report on the current scientific evidence on the effectiveness of this technology in the prevention of severe hypoglycemia and hypoglycemia unawareness. RECENT FINDINGS: Recent studies have found that the integration of CGM with continuous subcutaneous insulin infusion (CSII) therapy, a system known as sensor-augmented pump (SAP) therapy, very significantly reduces the occurrence of these conditions by providing real-time glucose readings/trends and automatically suspending insulin infusion when glucose is low (LGS) or, even, before glucose is low but is predicted to soon be low (PLGS). Initial data indicate that even for patients with type 1 diabetes treated with multiple daily injections, real-time CGM alone has been found to reduce both severe hypoglycemia and hypoglycemia unawareness. Closed loop systems (artificial pancreas) comprised of CGM and CSII without patient intervention to adjust basal insulin, which automatically reduce, increase, and suspend insulin delivery, represent a potential new option that is moving toward becoming a reality in the near future. Sensor technology promises to continue to improve patients' lives not only by attaining glycemic control but also by reducing hypoglycemia, a goal best achieved in conjunction with structured individualized patient education.

Unawareness for Motor Impairment and Distorted Perception of Task Difficulty.

OBJECTIVES: Anosognosia for motor impairment is a complex syndrome that can manifest itself under different forms, guiding patients' behavior and task decisions. However, current diagnostic tools tend to evaluate only more explicit aspects of anosognosia (asking the patients about their motor abilities) and fail to address more subtle features of awareness. We have developed a new assessment measure, the ECT (Errand Choice Test), where patients are asked to judge task difficulty rather than estimate their own impairment. METHODS: We assessed awareness in a group of 73 unilateral left- and right-brain damaged (30 LBD and 43 RBD, respectively) patients by means of the VATAm, which explicitly requires them to evaluate their own motor abilities, and the ECT. A control group of 65 healthy volunteers was asked to perform the ECT under two conditions: Current condition (i.e., using both hands) and Simulated conditions (i.e., simulating hemiplegia). RESULTS: A total of 27% of the patients showed different performance on the VATAm and ECT, 21% of the patients showing lack of awareness only on VATAm and 6% only on ECT. Moreover, despite the ECT identified a higher frequency of anosognosia after RBD (33.3%) than LBD (27.6%), this hemispheric asymmetry was not significant. Remarkably, anosognosic patients performed very similarly to controls in the "current condition", suggesting that anosognosic patients' ability to perceive the complexity of each task per se is not altered. CONCLUSION: Different methods may be able to tackle different aspects of awareness and the ECT proved to be able to detect less evident forms of awareness. (JINS, 2018, 24, 45-56).

Vegetative state outcomes improved over the last two decades.

OBJECTIVE: To describe late outcomes in patients with prolonged unawareness, and factors affecting them. DESIGN: A retrospective study of 154 patients with traumatic brain injury (TBI) and 52 with non-traumatic brain injury (NTBI), admitted for intensive care and consciousness rehabilitation (ICCR), in a vegetative state (VS) lasting over 1 month. RESULTS: Survival rate (67% total) was higher than in past studies carried out at the same facility (p < 0.01). Consciousness recovery rate (54% total) was higher in NTBI VS patients (p < 0.01) than in earlier cohorts, and similar in TBI VS patients, despite their older age than that of earlier cohorts. No meaningful differences were found in characteristics or in outcomes between the TBI and NTBI groups. Age, length of stay in ICCR, and hydrocephalus were found to affect survival (p < 0.001). Younger age, absence of hydrocephalus, and anti-Parkinsonian medication contributed to consciousness recovery after VS (p < 0.05). CONCLUSIONS: The present study demonstrated an improvement in survival and recovery of consciousness in VS patients over the last two decades, and similar outcomes for both TBI and NTBI VS. Outcomes suggest that acute medical care and ICCR have contributed to advances in VS care.

Quantum Games with Unawareness.

Games with unawareness model strategic situations in which players' perceptions about the game are limited. They take into account the fact that the players may be unaware of some of the strategies available to them or their opponents as well as the players may have a restricted view about the number of players participating in the game. The aim of the paper is to introduce this notion into theory of quantum games. We focus on games in strategic form and Eisert-Wilkens-Lewenstein type quantum games. It is shown that limiting a player's perception in the game enriches the structure of the quantum game substantially and allows the players to obtain results that are unattainable when the game is played in a quantum way by means of previously used methods.