Cognitive, neurophysiologic and metabolic sequelae of previous hypoglycemic coma revealed by hyperinsulinemic-hypoglycemic clamp in type 1 diabetic patients.

To examine the relationship between electroencephalographic (EEG) activity and hypoglycemia unawareness, we investigated early parameters of vigilance and awareness of various symptom categories in response to hypoglycemia in intensively treated type 1 diabetic (T1DM) patients with different degrees of hypoglycemia unawareness. Hypoglycemia was induced with a hyperinsulinemic-hypoglycemic clamp in six T1DM patients with a history of hypoglycemia unawareness previous severe hypoglycemic coma (SH) and in six T1DM patients without (C) history of hypoglycemia unawareness previous severe hypoglycemic coma. Cognitive function tests (four choice reaction time), counterregulatory responses (adrenaline), and symptomatic responses were evaluated at euglycemia (90 mg/dl) and during step-wise plasma glucose reduction (68, 58 and 49 mg/dl). EEG activity was recorded continuously throughout the study and analyzed by spectral analysis. Cognitive function deteriorated significantly at a glucose threshold of 55 ± 1 mg/dl in both groups (p = ns) during hypoglycemia, while the glucose threshold for autonomic symptoms was significantly lower in SH patients than in C patients (49 ± 1 vs. 54 ± 1 mg/dl, p < 0.05, respectively). In SH patients, eye-closed resting EEG showed a correlation between the mean dominance frequency and plasma glucose (r = 0.62, p < 0.001). Theta relative power increased during controlled hypoglycemia compared to euglycemia (21.6 ± 6 vs. 15.5 ± 3% Hz p < 0.05) and was higher than in the C group (21.6 ± 6 vs. 13.8 ± 3%, p < 0.03). The cognitive task beta activity was lower in the SH group than in the C group (14.8 ± 3 Hz, vs. 22.6 ± 4 vs. p < 0.03). Controlled hypoglycemia elicits cognitive dysfunction in both C and SH patients; however, significant EEG alterations during hypoglycemia were detected mainly in patients with a history of hypoglycemia unawareness and previous severe hypoglycemic coma. These data suggest that prior episodes of hypoglycemic coma modulate brain electric activity.

Psychometric and EEG changes after carotid endarterectomy.

The influence of carotid stenosis and its surgical treatment on brain function is still poorly defined. We therefore performed a study to assess psychometric and quantified EEG findings after carotid endarterectomy (CEA). Sixty-nine non-demented patients (aged 72 ± 7 years) with severe carotid stenosis (≥ 70%) eligible for CEA were studied. Forty patients (group A) had unilateral stenosis, and 29 patients (group B) had bilateral stenosis. Before and 5 months after CEA all the patients were evaluated by the Trail Making Test A, the Symbol Digit Test, and spectral EEG analysis. At baseline, compared to group A, group B patients performed slowly the Trail Making Test A (Z: 1.45 ± 1.4 vs. 0.76 ± 1.3; p < 0.05), but not the Symbol Digit Test (Z: 0.83 ± 1.38 vs. 0.64 ± 1.26; p = 0.59). Altogether, the patients with at least one abnormal psychometric test were 29% (group A: 26%; group B: 33%, p = 0.56). The EEG did not differ significantly between patients of group A compared to group B. After CEA, psychometric tests improved (mean Z score from 0.73 ± 1.12 to 0.45 ± 1.15, p < 0.05). The improvement was similar in group A and B. The EEG mean dominant frequency improved only in group B patients and it was related to the improvement in psychometric tests (r = 0.43, p = 0.05). Low psychometric performance was detectable in about 1/ 3 of non-demented patients with severe carotid stenosis. CEA improved mental performance and, in patients with severe bilateral stenosis, accelerated the EEG frequency.

The moderating role of depressive symptoms in the association between heart rate variability and cognitive performance in cardiac patients.

INTRODUCTION: Coronary heart disease (CHD) is strongly associated with cognitive impairment, which is a core feature of depression, highly prevalent in patients with CHD. Interestingly, patients with CHD and individuals with depression display reduced heart rate variability (HRV), which proxies a complex network integrating autonomic and attentional systems. This study investigated the moderating role of depressive symptoms in the relation between reduced HRV and cognitive performance in patients with CHD. METHOD: The sample included 274 patients with CHD (mean [standard deviation] age = 62 [9.5] years; 13 % women) admitted to cardiac rehabilitation units. Visual attention and task switching were assessed through the Trail Making Test (TMT). Depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II). Resting electrocardiographic recordings were collected to compute HRV indices. RESULTS: Patients with more severe depressive symptoms displayed an inverse association between HRV and cognitive performance (TMT-A: b = -0.08, p = .022; TMTB: b = -0.07, p = .042), whereas patients with milder depressive symptoms showed no significant association (TMT-A: b = -0.00, p = .90; TMTB: b = -0.02, p = .44). CONCLUSIONS: Depressive symptoms may strengthen the relation between reduced HRV and poorer cognitive performance in cardiac patients. The presence of depressive symptoms may signal the dysfunction of a network subserving autonomic and cognitive function.

The impact of COVID-19-related quarantine on psychological outcomes in patients after cardiac intervention: a multicenter longitudinal study.

Mandatory quarantine during the COVID-19 pandemic had substantial negative consequences on psychological health in the general population. Depression, anxiety, and insomnia were reported to increase the morbidity and mortality risk in cardiac patients after cardiac interventions. Nonetheless, a gap in the evidence appeared regarding the effects of COVID-19-related quarantine on psychological outcomes in patients after cardiac interventions. The present study aimed to longitudinally investigate the effects of quarantine on depressive, anxiety, and insomnia symptoms in a group of patients who underwent cardiac intervention. Seventy-three patients admitted for cardiac rehabilitation completed a psychological assessment before and a reassessment after the quarantine and were included in the quarantine group. The control group included 76 patients who completed both evaluations before the quarantine. Depressive (Beck Depression Inventory-II; BDI-II), anxiety (Beck Anxiety Inventory-II; BAI), and insomnia (Sleep Condition Indicator; SCI) symptoms were evaluated in both groups at one (assessment) and eight (reassessment) months after cardiac intervention. The statistical analyses revealed that at reassessment, the quarantine group showed higher global depressive, anxiety, and insomnia symptoms than the control group and increased cognitive symptoms of depression. A higher presence of clinically relevant depressed patients was seen in the quarantine group. The present results showed that the COVID-19-related mandatory quarantine negatively affected psychological outcomes in patients after cardiac intervention, increasing the probability for these patients to be depressed. This, in turn, could influence patients' health in a critical period for morbidity and mortality risk. This underlines the priority of integrating and improving targeted mental health support as the pandemic continues, especially for cardiac patients.

Mood, cognition and EEG changes during interferon alpha (alpha-IFN) treatment for chronic hepatitis C.

BACKGROUND: This study is aim to investigate concurrent long-term psychiatric, cognitive and neurophysiological measures of alpha-IFN neurotoxicity in the treatment of chronic viral hepatitis. METHODS: Twenty patients with HCV hepatitis were enrolled while treated with alpha-IFN (3-6 MU t.i.w. for 6-12 months). Neurotoxicity was evaluated by psychiatric [Hamilton Depression Rating Scale (HAM-D), Hamilton Scale for Anxiety (HAM-A), Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI-Y)], complete cognitive and neurophysiological assessments (EEG spectral analysis, P300). Patients were assessed at baseline (t0), 2 (t1) and 6 months (t2) since the beginning of therapy. RESULTS: Depression scores significantly increased (HAM-D: t0=4.4+/-2.6; t1=8.9+/-3.9, p<0.001; and t2=7.7+/-3.8, p<0.001). A concurrent increase was shown also for anxiety (HAM-A: t0=6.0+/-3.2; t1=9.6+/-4.5, p<0.005; and t2=9.1+/-4.5, p<0.005). Significant neurophysiological effects were also detected: increase of alpha power (p<0.05) in frontal derivations, reduction of the mean dominant frequency (p<0.005) and increase of theta power (p<0.05) in parietal derivations. In contrast, no significant cognitive changes occurred. LIMITATIONS: The study was performed on a relative small sample of patients mainly with observational intentions. Biological data (e.g. blood cytokines samples) are not available: they could have given useful information about biological mechanisms related to the alterations observed. CONCLUSIONS: Alpha-IFN treatment caused a time-dependent induction of symptoms of mild depression, concurrent anxiety and EEG changes. These psychiatric and neurophysiological changes can better explain the pharmacological profile of alpha-IFN and could help to address research on at risk population and, particularly, during pegylated-IFN therapy.

Attention dysfunction in cirrhotic patients: an inquiry on the role of executive control, attention orienting and focusing.

Attention alterations are reported in cirrhotics. Aiming at clarifying attention functioning in cirrhotics, an inquiry on the functioning of the anterior (AAS) and the posterior (PAS) attention system was performed. Thirty-six cirrhotics without overt hepatic encephalopathy (24 with EEG or TMT-A alterations) and 16 matched control subjects were enrolled. The AAS was studied by the Stroop task measuring selective attention control, the PAS was studied by the Posner task and the Focus task measuring automatic covert orienting and visual focusing of attention respectively. Cirrhotics presented a task-dependent psychomotor slowing (Stroop > Posner > Focus) with an increased percentage of errors in the incongruent condition of the Stroop task [F(1, 57) = 4.9, p < 0.03]. Class C patients had both a selective slowing [F(1, 33) = 4.3, p < 0.05] and an increased percentage of errors in the incongruent condition [F(1, 34) = 5.1, p < 0.05] compared to Class A-B patients and controls. The patients with an altered EEG performed the Stroop test significantly slowly than those without EEG alterations [F(1, 41) = 8.9, p < 0.01] and with a clear trend for a higher number of errors in the incongruent condition [F(1, 39) = 3.8, p < 0.06]. In contrast, attention orienting and focusing were maintained. In conclusion, the AAS is more sensitive than the PAS to the early stages of hepatic encephalopathy.

Effect of blood ammonia elevation following oral glutamine load on the psychometric performance of cirrhotic patients.

Oral glutamine challenge is a method to increase blood ammonia and may be used to study the ammonia lowering effect of drugs potentially useful in hepatic encephalopathy (HE). We tested its influence on the psychometric performance of 18 cirrhotic patients without HE. Twelve nonencephalopatic cirrhotic patients were studied before and after glutamine load (20 g in 100 mL tap water) and six patients before and after placebo (100 mL tap water) by using the Number Connection Test (NCT), the Covert Visual Attention Orienting Test (CVAOT), and the Scan Test (SCT). Blood ammonia increased significantly after glutamine (from 79 +/- 34 to 211 +/- 66 microg/dL) but not after placebo (from 94 +/- 41 to 88 +/- 26). No difference in the NCT was found before and after glutamine load or placebo. The CVAOT was similar after glutamine challenge and placebo, nor any interaction between Loads (glutamine or placebo) x Cue position was found, suggesting that glutamine load did not influence attention-orienting. SCT results were also similar after glutamine and placebo, suggesting a lack of influence on the working memory. Glutamine challenge is a safe method to induce hyperammonemia in nonencephalopatic cirrhotic patients and, therefore, to study the efficacy of ammonia lowering treatments.

Central nervous system alterations in liver cirrhosis: the role of portal-systemic shunt and portal hypoperfusion.

The role of portal-systemic shunting and portal liver hypoperfusion in the pathophysiology of central nervous system dysfunction (CNSD) of cirrhosis is not yet well defined. It is well known that one of the most important collateral vessels (CVs) is a patent paraumbilical vein (PUV), but there is controversy regarding its clinical significance. We have evaluated the relationships between neuropsychological and EEG alterations, ammonia plasma level (NH4), hepatic function, and portal hemodynamics (Doppler Ultrasound) in 95 cirrhotic patients. Patency, diameter, or flow of PUV or the presence of other CVs were not related to an increased prevalence of neuropsychological or EEG abnormalities. Patients with effective portal flow (EPF = portal flow - PUV flow) lower than 692 mL/min (median) had a significantly higher risk of failing the neuropsychological test, or of having an altered EEG. Low EPF and prothrombin time (<50%), and high NH4 (51 micromol/L) were independent predictors of an abnormal EEG. Considering both low EPF and the numerosity of CVs, only low EPF was found to explain EEG alterations. In conclusion, portal liver hypoperfusion and decreased liver function were associated with an increased risk of CNSD in cirrhotic patients, whereas PUV patency per se was not.

Central nervous system alterations in liver cirrhosis: the role of portal-systemic shunt and portal hypoperfusion.

The role of portal-systemic shunting and portal liver hypoperfusion in the pathophysiology of central nervous system dysfunction of cirrhosis is not yet well defined. It is well known that one of the most important collateral vessels (CV) is a patent paraumbilical vein (PUV) but there is controversy regarding its clinical significance. We have evaluated the relationships between neuropsychological and EEG alterations, ammonia plasma level (NH4), hepatic function, and portal hemodynamics (Doppler Ultrasound) in 95 cirrhotic patients. Patency, diameter, or flow of PUV or the presence of other CV were not related to an increased prevalence of neuropsychological or EEG abnormalities. Patients with effective portal flow (EPF = portal flow - PUV flow) lower than 692 mL/min (median) had a significantly higher risk of failing the neuropsychological test, or of having an altered EEG. Low EPF and prothrombin time (<50%), and high NH4 (> or = 51 micromol/L) were independent predictors of an abnormal EEG. Considering both low EPF and the numerosity of CV, only low EPF was found to explain EEG alterations. In conclusion, portal liver hypoperfusion and decreased liver function were associated with an increased risk of central nervous system dysfunction in cirrhotic patients, whereas PUV patency per se was not.

Variability of trail making test, symbol digit test and line trait test in normal people. A normative study taking into account age-dependent decline and sociobiological variables.

BACKGROUND AND AIMS: The influence of sociobiological variables and aging on the variability of the Trail Making Tests (TMT), the Symbol Digit Substituting Test (SDT), and the Line Trait Test (LTT) in the general healthy populations are not well known. Even less is known about the reliability at re-testing. This study aimed at determining the reference range of these tests, taking into account sociobiological variables and age, and the re-testing effect. METHODS: We studied 300 healthy subjects from 20 to 80 years of age. The sample was derived by the pooling of two samples stratified by age and sex: a randomized sample of 161 subjects collected from the city registers of Padova, and a convenience sample of 139 subjects collected in 20 towns (mainly rural) of Northern Italy. After normalization, data were assayed for the influence of age, education, job, and gender. RESULTS: Age was found to be a significant independent predictor for all the tests, education for all but the LTT, job only for the TMT-B and a geometrical version of the same test (TMT-G) which was proved to be highly correlated with the TMT-B (r=0.80, p<0.01). Job and the interaction age x education level influenced the difference TMT-B minus TMT-A. From the predicting equations, the normative data and the formulas to obtain Z scores for each test were derived. Reliability was lowest for LTT errors (CV=67%), highest for the SDT (13%), whereas the TMT obtained intermediate values (22-33%, depending on the test). CONCLUSIONS: This study provides the most reliable normative data range for the TMT, SDT and LTT to date because it considers important demographic variables such as age, education and job.

Comparison between two high-dose methylprednisolone schedules in the treatment of acute hepatic cellular rejection in liver transplant recipients: a controlled clinical trial.

Intravenous methylprednisolone is used in most liver transplant centers as first-line therapy of acute hepatic cellular rejection in patients who undergo liver transplant. However, no controlled study has been performed to date to define the optimal dose and duration of the steroid regimen. The schedules that actually are used in most transplant centers are drawn from those that were developed empirically for the treatment of acute renal graft rejection. Thus, the aim of the study was to compare two schedules of steroid treatment of acute hepatic cellular rejection among those most widely used. Thirty-eight eligible patients with grade II or III acute hepatic cellular rejection were randomized to receive two different high-dose methylprednisolone schedules. Eighteen patients were randomized in group A (intravenous dose of 1,000 mg of methylprednisolone followed by a 6-day taper from 200 to 20 mg/d). Twenty patients were randomized in group B (intravenous dose of 1,000 mg of methylprednisolone for three consecutive days). The response to treatment was evaluated by means of a second liver biopsy. The treatment of group A proved to be more effective than treatment of group B. The resolution of acute hepatic cellular rejection was observed in 83.3% of cases in group A and 50.0% of cases in group B (P <.05). The treatment of group A proved to be safer also than treatment of group B. Patients randomized in group B showed a higher prevalence of infections (90.0% of cases versus 55.5% of cases; P <.01) mainly because of bacterial (80.0% versus 50.0%; P <.05) and viral (50.0% versus 16.6%; P <.05) agents. In conclusion, the study shows that intravenous administration of 1,000 mg of methylprednisolone followed by a 6-day taper from 200 to 20 mg/d is more effective and safer than intravenous dose of 1,000 mg of methylprednisolone for three consecutive days in the treatment of acute cellular rejection in patients with liver transplantation.