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Hepatic Encephalopathy (HE) is a frequent complication in patients suffering from liver cirrhosis. HE comprises a variety of neuropsychiatric and motor symptoms. Increased ammonia levels have been suggested as a key factor in the disease pathology. Using animal models, Cauli and colleagues reported that hyperammonemia may lead to brain area depending alteration of GABAergic neurotransmission with an increase of GABAeric tone in the cerebellum and a decrease in the cerebral cortex. Consistent with this data, recent work from our group revealed a reduced GABAergic tone in the motor cortex of patients with manifest HE using transcranial magnetic stimulation (TMS). The aim of this study is to probe how GABAergic cerebellar tone is altered in patients at different stages of HE and how this alteration is related to clinical parameters such as the critical flicker frequency and ataxia scoring. Methods: 30 participants [15 patients with HE (5 minimal HE, 6 HE grade I, and 4 HE grade II) and 15 age matched healthy controls] were subjected to the following: 1-Critical flicker frequency (CFF) which is a sensitive and reliable parameter for quantification of low-grade HE in cirrhotic patients. 2- Cerebellar brain inhibition TMS paradigm (CBI): in this paradigm, a conditioning TMS pulse is applied over one hemisphere of the cerebellum followed by a test pulse over the contralateral motor cortex resulting in a motor evoked potential (MEP). In healthy subjects, the MEP is inhibited when the test stimulus is preceded by the conditioning stimulus at an interval between 5-7 ms through inhibition of the fascilitatory disynaptic dentato-thalamo-cortical pathway. 3- Score for assessment and rating of ataxia (SARA) to detect symptoms of cerebellar affection. Results: Cerebellar inhibition at ISI 5 to 7 ms was significantly reduced in patients with HE compared to healthy controls. However, the magnitude of cerebellar inhibition at 7 ms increased with disease severity and correlated with SARA score and with CFF by trend. Conclusion: Overall cerebellar inhibition is significantly reduced in patients with HE, suggesting affection of the dentato-thalamo-cortical pathway in this disease. However, the magnitude of cerebellar inhibition at 7 ms increases with disease severity and correlates with SARA score and with CFF by trend, supporting the hypothesis of disease stage dependent increase of GABAergic tone in the Purkinje cells. Our results are consistent with pervious animal in vitro data suggesting increased GABA-ergic tone in the cerebellum and decreased GABA-ergic tone in the motor cortex.

Hepatic Encephalopathy (HE) is a frequent complication in patients suffering from liver cirrhosis. HE comprises a variety of neuropsychiatric and motor symptoms. Increased ammonia levels have been suggested as a key factor in the disease pathology. Using animal models, Cauli and colleagues reported that hyperammonemia may lead to brain area depending alteration of GABAergic neurotransmission with an increase of GABAeric tone in the cerebellum and a decrease in the cerebral cortex. Consistent with this data, recent work from our group revealed a reduced GABAergic tone in the motor cortex of patients with manifest HE using transcranial magnetic stimulation (TMS). The aim of this study is to probe how GABAergic cerebellar tone is altered in patients at different stages of HE and how this alteration is related to clinical parameters such as the critical flicker frequency and ataxia scoring. Methods: 30 participants [15 patients with HE (5 minimal HE, 6 HE grade I, and 4 HE grade II) and 15 age matched healthy controls] were subjected to the following: 1-Critical flicker frequency (CFF) which is a sensitive and reliable parameter for quantification of low-grade HE in cirrhotic patients. 2- Cerebellar brain inhibition TMS paradigm (CBI): in this paradigm, a conditioning TMS pulse is applied over one hemisphere of the cerebellum followed by a test pulse over the contralateral motor cortex resulting in a motor evoked potential (MEP). In healthy subjects, the MEP is inhibited when the test stimulus is preceded by the conditioning stimulus at an interval between 5-7 ms through inhibition of the fascilitatory disynaptic dentato-thalamo-cortical pathway. 3- Score for assessment and rating of ataxia (SARA) to detect symptoms of cerebellar affection. Results: Cerebellar inhibition at ISI 5 to 7 ms was significantly reduced in patients with HE compared to healthy controls. However, the magnitude of cerebellar inhibition at 7 ms increased with disease severity and correlated with SARA score and with CFF by trend. Conclusion: Overall cerebellar inhibition is significantly reduced in patients with HE, suggesting affection of the dentato-thalamo-cortical pathway in this disease. However, the magnitude of cerebellar inhibition at 7 ms increases with disease severity and correlates with SARA score and with CFF by trend, supporting the hypothesis of disease stage dependent increase of GABAergic tone in the Purkinje cells. Our results are consistent with pervious animal in vitro data suggesting increased GABA-ergic tone in the cerebellum and decreased GABA-ergic tone in the motor cortex.

This study aimed to evaluate the left ventricular (LV) functions in a cohort of children with Graves’ disease (GD). This is a cross-sectional case-control study. It included 36 children with GD and 36 healthy children matched for age and gender. Thyroid hormones (TSH, FT4, and FT3) and antithyroid autoantibodies [anti-thyroid peroxidase (anti-TPO), thyrotropin receptor (TRAbs), and thyroglobulin antibodies] were measured. Conventional and tissue Doppler imaging (TDI) echocardiographies were used to assess left ventricular systolic and diastolic functions. LV mass index (LVMI) and myocardial performance index (MPI) were also measured. Compared to healthy children, conventional echocardiography of patients with GD revealed higher LVMI (P = 0.001) indicating LV hypertrophy but normal LV functions while TDI revealed lower Em/Am ratio indicating LV diastolic dysfunction (P = 0.001). Significant correlations were reported between FT4 with LVMI (P = 0.05), Em/Am (P = 0.01), and MPI (P = 0.01). In multivariate analysis, a positive correlation was identified between FT4 with MPI (OR = 1.17; 95% CI = 1.09–1.15; P = 0.001). Conclusions: Children with newly diagnosed GD may have significant subclinical changes in LV structure and function (diastolic and global). TDI is more sensitive than conventional Doppler in detecting LV dysfunction. These findings highlight the importance of early monitoring of children with GD for left ventricular mass index and diastolic function. What is Known: • There is an increased risk for cardiac abnormalities in children with Graves’ disease (GD). • Limited studies assessed left ventricular function in patients with GD. What is New: • Children with newly diagnosed GD may have significant subclinical changes in left ventricular structure and functions. • Children with newly diagnosed GD should be monitored for left ventricular mass index and diastolic function.

This study aimed to evaluate the left ventricular (LV) functions in a cohort of children with Graves’ disease (GD). This is a cross-sectional case-control study. It included 36 children with GD and 36 healthy children matched for age and gender. Thyroid hormones (TSH, FT4, and FT3) and antithyroid autoantibodies [anti-thyroid peroxidase (anti-TPO), thyrotropin receptor (TRAbs), and thyroglobulin antibodies] were measured. Conventional and tissue Doppler imaging (TDI) echocardiographies were used to assess left ventricular systolic and diastolic functions. LV mass index (LVMI) and myocardial performance index (MPI) were also measured. Compared to healthy children, conventional echocardiography of patients with GD revealed higher LVMI (P = 0.001) indicating LV hypertrophy but normal LV functions while TDI revealed lower Em/Am ratio indicating LV diastolic dysfunction (P = 0.001). Significant correlations were reported between FT4 with LVMI (P = 0.05), Em/Am (P = 0.01), and MPI (P = 0.01). In multivariate analysis, a positive correlation was identified between FT4 with MPI (OR = 1.17; 95% CI = 1.09–1.15; P = 0.001). Conclusions: Children with newly diagnosed GD may have significant subclinical changes in LV structure and function (diastolic and global). TDI is more sensitive than conventional Doppler in detecting LV dysfunction. These findings highlight the importance of early monitoring of children with GD for left ventricular mass index and diastolic function. What is Known: • There is an increased risk for cardiac abnormalities in children with Graves’ disease (GD). • Limited studies assessed left ventricular function in patients with GD. What is New: • Children with newly diagnosed GD may have significant subclinical changes in left ventricular structure and functions. • Children with newly diagnosed GD should be monitored for left ventricular mass index and diastolic function.

Background Obese children are at increased risk for abnormal cardiac structure and function. Little is known about adrenomedullin (AM), a cytokine produced in various organs and tissues, as a biomarker of cardiac hypertrophy in obese children. This study aimed to assess the plasma AM levels in a cohort of obese children and its relationship to left ventricular (LV) functions. Methods The study included 60 obese children and 60 non-obese children matched for age and gender as control group. Blood pressure, serum lipid profile, fasting glucose, insulin and plasma AM and the homeostatic model assessment of insulin resistance (HOMA-IR) were measured. Cardiac dimensions and LV functions were assessed using conventional echocardiography. Results Compared to control subjects, obese children had higher blood pressure (P = 0.01), insulin (P = 0.001), HOMA-IR (P = 0.001), and AM (P = 0.001). Moreover, obese children had higher LV mass index (LVMI) (P = 0.001), indicating LV hypertrophy; prolonged isovolumic relaxation times (P = 0.01), prolonged mitral deceleration time (DcT) (P = 0.01) and reduced ratio of mitral E-to-mitral A-wave peak velocity (P = 0.01), indicating LV diastolic dysfunction. Laboratory abnormalities were only present in children with LV hypertrophy. In multivariate analysis in obese children with LV hypertrophy, AM levels were positively correlated with LVMI [odds ratio (OR) 1.14, 95% confidence interval (Cl) 1.08–1.13, P = 0.0001] and mitral DcT (OR 2.25, 95% CI 1.15–2.05, P = 0.01) in the presence of higher blood pressure and HOMA-IR. A cut-off value of AM at 52 pg/mL could differentiate obese children with and without left ventricular hypertrophy at a sensitivity of 94.32% and specificity of 92.45%. Conclusions Plasma AM levels may be elevated in obese children particularly those with LV hypertrophy and is correlated with higher blood pressure and insulin resistance. Measurement of plasma AM levels in obese children may help to identify those at high risk of developing LV hypertrophy and dysfunction.

Background Obese children are at increased risk for abnormal cardiac structure and function. Little is known about adrenomedullin (AM), a cytokine produced in various organs and tissues, as a biomarker of cardiac hypertrophy in obese children. This study aimed to assess the plasma AM levels in a cohort of obese children and its relationship to left ventricular (LV) functions. Methods The study included 60 obese children and 60 non-obese children matched for age and gender as control group. Blood pressure, serum lipid profile, fasting glucose, insulin and plasma AM and the homeostatic model assessment of insulin resistance (HOMA-IR) were measured. Cardiac dimensions and LV functions were assessed using conventional echocardiography. Results Compared to control subjects, obese children had higher blood pressure (P = 0.01), insulin (P = 0.001), HOMA-IR (P = 0.001), and AM (P = 0.001). Moreover, obese children had higher LV mass index (LVMI) (P = 0.001), indicating LV hypertrophy; prolonged isovolumic relaxation times (P = 0.01), prolonged mitral deceleration time (DcT) (P = 0.01) and reduced ratio of mitral E-to-mitral A-wave peak velocity (P = 0.01), indicating LV diastolic dysfunction. Laboratory abnormalities were only present in children with LV hypertrophy. In multivariate analysis in obese children with LV hypertrophy, AM levels were positively correlated with LVMI [odds ratio (OR) 1.14, 95% confidence interval (Cl) 1.08–1.13, P = 0.0001] and mitral DcT (OR 2.25, 95% CI 1.15–2.05, P = 0.01) in the presence of higher blood pressure and HOMA-IR. A cut-off value of AM at 52 pg/mL could differentiate obese children with and without left ventricular hypertrophy at a sensitivity of 94.32% and specificity of 92.45%. Conclusions Plasma AM levels may be elevated in obese children particularly those with LV hypertrophy and is correlated with higher blood pressure and insulin resistance. Measurement of plasma AM levels in obese children may help to identify those at high risk of developing LV hypertrophy and dysfunction.

Background Obese children are at increased risk for abnormal cardiac structure and function. Little is known about adrenomedullin (AM), a cytokine produced in various organs and tissues, as a biomarker of cardiac hypertrophy in obese children. This study aimed to assess the plasma AM levels in a cohort of obese children and its relationship to left ventricular (LV) functions. Methods The study included 60 obese children and 60 non-obese children matched for age and gender as control group. Blood pressure, serum lipid profile, fasting glucose, insulin and plasma AM and the homeostatic model assessment of insulin resistance (HOMA-IR) were measured. Cardiac dimensions and LV functions were assessed using conventional echocardiography. Results Compared to control subjects, obese children had higher blood pressure (P = 0.01), insulin (P = 0.001), HOMA-IR (P = 0.001), and AM (P = 0.001). Moreover, obese children had higher LV mass index (LVMI) (P = 0.001), indicating LV hypertrophy; prolonged isovolumic relaxation times (P = 0.01), prolonged mitral deceleration time (DcT) (P = 0.01) and reduced ratio of mitral E-to-mitral A-wave peak velocity (P = 0.01), indicating LV diastolic dysfunction. Laboratory abnormalities were only present in children with LV hypertrophy. In multivariate analysis in obese children with LV hypertrophy, AM levels were positively correlated with LVMI [odds ratio (OR) 1.14, 95% confidence interval (Cl) 1.08–1.13, P = 0.0001] and mitral DcT (OR 2.25, 95% CI 1.15–2.05, P = 0.01) in the presence of higher blood pressure and HOMA-IR. A cut-off value of AM at 52 pg/mL could differentiate obese children with and without left ventricular hypertrophy at a sensitivity of 94.32% and specificity of 92.45%. Conclusions Plasma AM levels may be elevated in obese children particularly those with LV hypertrophy and is correlated with higher blood pressure and insulin resistance. Measurement of plasma AM levels in obese children may help to identify those at high risk of developing LV hypertrophy and dysfunction.

Neuron-specific enolase is a sensitive marker of neuronal damage in various neurologic disorders. This study aimed to measure serum neuron-specific enolase levels at different time points and severities of diabetic ketoacidosis. This study included 90 children (age 9.2 + 3.4 years) with diabetic ketoacidosis. Neuron-specific enolase was measured at 3 time points (baseline and after 12 and 24 hours of starting treatment). Among patients, 74.4% had diagnosis of new diabetes, 60% had Glasgow Coma Scale score 15, and 75.6% had moderate/severe diabetic ketoacidosis. Compared with controls (n ¼ 30), children with diabetic ketoacidosis had higher neuron-specific enolase levels at the 3 time points (P ¼ .0001). In multiple regression analysis, the factors associated with higher neuron-specific enolase levels were younger age, higher glucose, lower pH, and bicarbonate values. This study indicates that serum neuron-specific enolase is elevated in diabetic ketoacidosis and correlated with the severity of hyperglycemia, ketosis, and acidosis. This study indicates that diabetic ketoacidosis may cause neuronal injury from which the patients recovered partially but not completely.

Neuron-specific enolase is a sensitive marker of neuronal damage in various neurologic disorders. This study aimed to measure serum neuron-specific enolase levels at different time points and severities of diabetic ketoacidosis. This study included 90 children (age 9.2 + 3.4 years) with diabetic ketoacidosis. Neuron-specific enolase was measured at 3 time points (baseline and after 12 and 24 hours of starting treatment). Among patients, 74.4% had diagnosis of new diabetes, 60% had Glasgow Coma Scale score 15, and 75.6% had moderate/severe diabetic ketoacidosis. Compared with controls (n ¼ 30), children with diabetic ketoacidosis had higher neuron-specific enolase levels at the 3 time points (P ¼ .0001). In multiple regression analysis, the factors associated with higher neuron-specific enolase levels were younger age, higher glucose, lower pH, and bicarbonate values. This study indicates that serum neuron-specific enolase is elevated in diabetic ketoacidosis and correlated with the severity of hyperglycemia, ketosis, and acidosis. This study indicates that diabetic ketoacidosis may cause neuronal injury from which the patients recovered partially but not completely.