Search

Introduction: An early detection of low-grade hepatic encephalopathy (HE) is of high importance. The aim of the study was to compare a neuropsychological with a psychophysical test on the basis of the psychometric hepatic encephalopathy score (PHES) regarding effectiveness in diagnosing minimal HE (MHE). Methods: In our prospective controlled observational study, we examined a total of 103 patients with liver cirrhosis for HE. The PHES, CFF, and EncephalApp were performed in all patients. Graduation was based on the result of the PHES. Patients without evidence for HE 1&2 according to the mental state (West-Haven criteria) with a PHES <−4 value points and no clinical symptoms were defined as having MHE. Patients were considered as HE0 when in the PHES none of the psychometric subtest results was abnormal or with a PHES ≥−4 value points. Patients with clinical symptoms were considered HE 1&2 patients. Different cut-off values were determined, and their specificity and sensitivity were calculated. Results: Ninety-six of the involved patients had liver cirrhosis and 25 acted as a healthy control group. The ROC analysis for the classification resulted in an AUC of 0.806, with the highest Youden index for the cut-off time >224 s, for which the sensitivity was 82% and the specificity 75%. Cases of withdrawals were seen in 10.74% of all tested patients. Conclusion: The EncephalApp distinguishes well between HE0 and MHE but has its limitations in grading higher forms of HE. Diagnosis using only the EncephalApp is not sufficient. [ABSTRACT FROM AUTHOR]

Neuropsychological and psychophysical tests are recommended to assess the risk of overt hepatic encephalopathy (OHE), but their accuracy is limited. Hyperammonaemia is central in the pathogenesis of OHE, but its predictive utility is unknown. In this study, we aimed to determine the role of neuropsychological or psychophysical tests and ammonia, and to develop a model (AMMON-OHE) to stratify the risk of subsequent OHE development in outpatients with cirrhosis. This observational, prospective study included 426 outpatients without previous OHE from three liver units followed for a median of 2.5 years. Psychometric hepatic encephalopathy score (PHES) <-4 or critical flicker frequency (CFF) <39 was considered abnormal. Ammonia was normalized to upper limit of normal (AMM-ULN) at the respective reference laboratory. Multivariable frailty competing risk and random survival forest analyses were performed to predict future OHE and to develop the AMMON-OHE model. External validation was carried out using 267 and 381 patients from two independent units. Significant differences were found in time-to-OHE (log-rank p <0.001) according to PHES or CFF and ammonia, with the highest risk in patients with abnormal PHES plus high AMM-ULN (hazard ratio 4.4; 95% CI 2.4-8.1; p <0.001 compared with normal PHES and AMM-ULN). On multivariable analysis, AMM-ULN but not PHES or CFF was an independent predictor of the development of OHE (hazard ratio 1.4; 95% CI 1.1-1.9; p = 0.015). The AMMON-OHE model (sex, diabetes, albumin, creatinine and AMM-ULN) showed a C-index of 0.844 and 0.728 for the prediction of a first episode of OHE in two external validation cohorts. In this study, we developed and validated the AMMON-OHE model, comprising readily available clinical and biochemical variables that can be used to identify outpatients at the highest risk of developing a first episode of OHE. In this study, we aimed to develop a model to predict which patients with cirrhosis are at risk of developing overt hepatic encephalopathy (OHE). Using data from three units and including 426 outpatients with cirrhosis, we developed the AMMON-OHE model – comprising sex, diabetes, albumin, creatinine and ammonia levels – which demonstrated good predictive ability. The AMMON-OHE model performs better than PHES and CFF to predict the first episode of OHE in outpatients with cirrhosis. This model was validated in 267 and 381 patients from two independent liver units. The AMMON-OHE model is available online for clinical use. [Display omitted] • Neither PHES nor CFF are independent predictors of a first episode of OHE. • Ammonia levels above the upper limit of normal are independently associated with the risk of developing OHE. • The best model to predict a first episode of OHE (the AMMON-OHE model) includes sex, diabetes, albumin, creatinine and ammonia. • The AMMON-OHE model performs better than PHES and CFF to predict the first episode of OHE in outpatients with cirrhosis. • The AMMON-OHE model showed good predictive accuracy in two separate external validation cohorts. [ABSTRACT FROM AUTHOR]

Objectives: Computer usage has rapidly grown. This is because it helps to resolve problems, i.e., encountered in daily life by individuals. Various monitor screens that have been developed affect the user’s eyes. Screen size is one of the relevant impacts. Thus, this study compared the immediate effects of two computer screen sizes on visual fatigue in Video Display Terminal (VDT) users. Methods: Twenty female VDT users participated in this study. Using a randomized block design for the study, the study participants randomly drew a ballot to determine the order of using an 18.5-inch and 23-inch computer screen size. The research participants were assessed by a visual fatigue score, critical flicker frequency, and dry eye score before and after using both computer screen sizes. They were tested in an ergonomic computer workstation for 2 hours. Besides, where they rested between each workstation for ≥30 minutes or until presetting no eye fatigue symptoms. The relevant data were compared between before and after using the computers and between the two different screen sizes. Results: The collected results suggested no significant difference in the visual fatigue score, critical flicker frequency, and dry eye score between using either computer screen sizes (P>0.05). However, there were significant differences in the visual fatigue score, critical flicker frequency, and dry eye score between before and after computer screen usage (P

Background Uremic encephalopathy is defined as cerebral dysfunction due to toxin accumulation in patients with chronic kidney disease (CKD). This condition is characterized by subtle to florid symptoms, and its clinical course is always progressive when untreated but partially reversible with renal replacement therapy. While no test exists to measure subclinical uremic encephalopathy, two tests have been validated to measure minimal hepatic encephalopathy: the critical flicker frequency (CFF) test and the psychometric hepatic encephalopathy score (PHES). Objective To use CFF and PHES to measure the prevalence of cerebral dysfunction in individuals with CKD. Methods This cross-sectional study included a total of 69 patients with stage-5 CKD. Cutoff points for minimal encephalopathy were established using existing clinical guidelines: ≤39 Hz for CFF and

Introduction: Hepatic encephalopathy (HE), in the context of liver cirrhosis, seems to result from low-grade cerebral edema of the astrocytes. Serum brain biomarkers S-100-beta und neuron-specific enolase (NSE) are often elevated in brain injury. We hypothesized that neuromarkers S-100-beta and NSE can be used in the diagnosis of HE, compared with standardized diagnostic tools. Material and Methods: A prospective non-randomized intervention study was performed using L-ornithine-L-aspartate (LOLA) for HE treatment. Primary endpoint was the evaluation of neuromarkers S-100-beta and NSE for detection and diagnosis of follow-up of HE. As secondary endpoints, the efficacy of LOLA on the course of HE and the diagnostic role of Portosystemic-Encephalopathy-Syndrome score (PHES) and critical flicker frequency (CFF) were analyzed. For diagnosis of covert (CHE) and overt (OHE) HE, West-Haven criteria (WHC), PHES and CFF were assessed at study entry. LOLA was applied (20 g i.v.) for 6 days. At the end of the study, HE evaluation was repeated. S-100-beta, NSE and ammonia were assessed in each patient before, during and after therapy with LOLA. Results: 30 patients were included. At study entry, CHE was diagnosed in 50% and OHE in 50% of all subjects. A total of 25 participants completed the study. After LOLA therapy, deterioration of HE occurred in

The relationship between luminous intensity and the maximum frequency of flicker that can be detected defines the limits of the temporal-resolving ability of the human visual system, and characterizing it has important theoretical and practical applications; particularly for determining the optimal refresh rate for visual displays that would avoid the visibility of flicker and other temporal artifacts. Previous research has shown that this relationship is best described by the Ferry–Porter law, which states that critical flicker fusion (CFF) increases as a linear function of log retinal illuminance. The existing experimental data showed that this law holds for a wide range of stimuli and up to 10,000 Trolands; however, beyond this, it was not clear if the CFF continued to increase linearly or if the function saturated. Our aim was to extend the experimental data available to higher light intensities than previously reported in the literature. For this, we measured the peripheral CFF at a range of illuminances over six orders of magnitude. Our results showed that for up to 104 Trolands, the data conformed to the Ferry–Porter law with a similar slope, as previously established for this eccentricity; however, at higher intensities, the CFF function flattens and saturates at ~90 Hz for a target size of 5.7 degrees, and at ~100 Hz for a target of 10 degrees of angular size. These experimental results could prove valuable for the design of brighter visual displays and illumination sources that are temporally modulated.

Uremic encephalopathy is defined as cerebral dysfunction due to toxin accumulation in patients with chronic kidney disease (CKD). This condition is characterized by subtle to florid symptoms, and its clinical course is always progressive when untreated but partially reversible with renal replacement therapy. While no test exists to measure subclinical uremic encephalopathy, two tests have been validated to measure minimal hepatic encephalopathy: the critical flicker frequency (CFF) test and the psychometric hepatic encephalopathy score (PHES). To use CFF and PHES to measure the prevalence of cerebral dysfunction in individuals with CKD. This cross-sectional study included a total of 69 patients with stage-5 CKD. Cutoff points for minimal encephalopathy were established using existing clinical guidelines: ≤39 Hz for CFF and < −4 for PHES. All participants were also screened for cognitive function and depression. Eighteen cases (26.1%) of cerebral dysfunction linked to uremic encephalopathy were detected with CFF, while twelve (17.4%) were detected by PHES; only six cases (8.7%) were diagnosed by both methods. Half of the cases (50%) had diabetes, and 61% were on hemodialysis. Cognitive function scores did not differ significantly between those receiving dialysis, hemodialysis, or no renal replacement therapy. It is essential to identify cerebral dysfunction when uremic encephalopathy is in early subclinical stages to reduce preventable events as traffic and work accidents. [ABSTRACT FROM AUTHOR]

Background: Psychometric hepatic encephalopathy score (PHES) needs local standardization. Aims: This study aimed at standardizing PHES for Turkish patients and compare them with German norms; to determine minimal hepatic encephalopathy (mHE) prevalence with two different methods [PHES battery and Critical Flicker Frequency (CFF)] and to assess whether sub-tests of the battery can be used for screening for mHE. Methods: Healthy volunteers (n = 816; 400 male) and cirrhotics (n = 124; 58 male) were included. For mHE diagnosis PHES score threshold was set at ≤ − 5 points and that of CFF at < 39 Hz. For comparing German and Turkish norms, datasets were combined. Multiple backward procedure was applied to assess effects of age, sex and education on single tests of the battery. Receiver operating characteristic (ROC) curves were created for assessing diagnostic capabilities of subtests of the battery. Results: PHES norms for Turks were developed. MHE prevalence in compensated cirrhotics was 29.8% and 27.4% with PHES and CFF tests, respectively, with low compatibility (kappa coefficient 0.389); mHE prevalence decreased to 16% when both tests were combined. Turks performed worse vs Germans in the digit symbol (DS) and serial dotting (SD) subtests but performed better in other subtests. In ROC analyzes of subtests, the combination of DS + SD tests achieved an AUROC of 0.974 versus PHES. Conclusions: Use of two methods for diagnosing mHE is important for research purposes. From a clinical perspective, sensitivity with acceptable specificity may suffice for screening instruments for mHE. Combined use of DS and SD subtests of the PHES battery appears suitable for this purpose. [ABSTRACT FROM AUTHOR]

• Transcranial magnetic stimulation was used to study synaptic plasticity in patients with manifest hepatic encephalopathy. • Patients with hepatic encephalopathy exhibited decreased synaptic plasticity of the primary motor cortex. • This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia. Hepatic encephalopathy (HE) is a potentially reversible brain dysfunction caused by liver failure. Altered synaptic plasticity is supposed to play a major role in the pathophysiology of HE. Here, we used paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), a transcranial magnetic stimulation (TMS) protocol, to test synaptic plasticity of the motor cortex in patients with manifest HE. 23 HE-patients and 23 healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were assessed as measure for cortical excitability. Time courses of MEP amplitude changes after the PAS25 intervention were compared between both groups. MEP-amplitudes increased after PAS25 in the control group, indicating PAS25-induced synaptic plasticity in healthy controls, as expected. In contrast, MEP-amplitudes within the HE group did not change and were lower than in the control group, indicating no induction of plasticity. Our study revealed reduced synaptic plasticity of the primary motor cortex in HE. Reduced synaptic plasticity in HE provides a link between pathological changes on the molecular level and early clinical symptoms of the disease. This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia in HE patients. [ABSTRACT FROM AUTHOR]

• Hepatic vascular malformations (HVMs) observed in HHT include portosystemic shunts. • The presence of radiologically undetectable HVMs is reported in the literature. • HVMs can cause portosystemic encephalopathy (PSE). • Using specific neurological tests we identified subclinical PSE in HHT patients. • These neurological tests should be adopted in HHT surveillance protocols. Background. Portosystemic shunts in Hereditary Haemorrhagic Telangiectasia (HHT) are often overlooked by conventional imaging although they could reduce hepatic clearance of gut-derived toxins. Aims. To evaluate, the presence of subclinical neurological alterations (SNAs), that we named "minimal portosystemic encephalopathy" (mPSE) in HHT patients without advanced liver disease (ALD). Methods. In this cross sectional study, consecutive HHT outpatients were firstly screened by critical flicker frequency (CFF) test (abnormal ≤39Hz), and the simplified animal naming test (S-ANT 1) (abnormal <15) was used to confirm the diagnosis of mPSE. Furthermore, we evaluated the effect of lactulose administration on mPSE. Multi-slice CT, cerebral dynamic magnetic resonance, laboratory analyses and transient elastography were also used. Results. None of the 37 enrolled patients showed portosystemic shunts at imaging techniques. However, 33 patients had normal CFF values (CFF-) and 4 displayed CFF alterations (37.0±0.7Hz, CFF+). The S-ANT 1 confirmed an impaired neurological performance (10.2±2.8) in CFF+ patients thus confirming the presence of mPSE. Noteworthy, lactulose administration determined a CFF increase (39.1±0.4Hz) and S-ANT 1 normalization in these patients. Neither mPSE- nor mPSE+ patients had ALD and showed similar demographic, clinical and laboratory parameters. Finally, no mPSE+ patient showed radiologically-detectable brain vascular malformations or other brain abnormalities at imaging. Conclusions. HHT patients represent a human model of mPSE secondary to portosystemic shunts escaping radiological detection. mPSE evaluation should be incorporated in HHT surveillance protocols since it can affect both health-related/social aspects and pharmacokinetics of orally administered drugs with a narrow therapeutic index and high hepatic first-pass uptake. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction and aims: To determine the prevalence of minimal hepatic encephalopathy(MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE. Materials and methods: We performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment. Results: 64 patients were included. 51.6% were male, the median age was 62 years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8 kPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9 mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24 weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p

Introduction: Minimal hepatic encephalopathy (MHE) represents one of the most overlooked complications of liver cirrhosis. Aim of the study: To compare the utility and efficacy of different MHE diagnostic modalities. Material and methods: This case-control study was conducted on hepatitis C virus (HCV)-related compensated cirrhotic patients. The Psychometric Hepatic Encephalopathy Score (PHES) was used to assign patients to MHE and controls. All patients were subjected to plasma ammonia, serum 3-nitrotyrosine (3-NT), critical flicker frequency (CFF), and the modified inhibitory control test (ICT). Results: CFF was significantly lower in the control group (38.5, 40 Hz, p = 0.003). The unweighted lures on ICT were 8.7, 4.9 in MHE and controls (p < 0.001). Moreover, ammonia was higher in the MHE group (89, 61.5 µmol/l, p < 0.001). 3-NT was also higher in the MHE group (31.5, 13.7 nmol/l, p < 0.001) respectively. CFF at cutoff < 39 Hz had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 57.5%, 77.5%, 71.9% and 64.6%, respectively; in modified ICT, at cutoff > 5 unweighted lures the values were 87.5%, 80%, 81.4% and 86.5%, respectively; in ammonia, at cutoff ≥ 76.45 µmol/l the values were 65%, 72.5%, 70.3% and 67.4%, respectively; for 3-NT at cutoff ≥ 14.15 nmol/l the values were 85%, 82.5%, 82.9% and 84.6%, respectively. The accuracy for MHE diagnosis was 67.5%, 83.3%, 68.8%, 83.8% relying on CFF, 3-NT, ammonia, and ICT respectively. On multivariate analysis, CFF < 39 Hz (OR = 10.2, p = 0.04), modified ICT > 5 unweighted lures (OR = 43.2, p = 0.002), and serum 3-NT levels ≥ 14.15 nmol/l (OR = 50.4, p < 0.001) were independent predictors of MHE. Conclusions: 3-NT and ICT are advantageous to reveal MHE in compensated liver cirrhosis, while CFF can be only used as adjuncts, with humble merits of ammonia [ABSTRACT FROM AUTHOR]

Background: alcohol may have additional neurotoxic ill-effects in patients with alcohol related cirrhosis apart from hepatic encephalopathy. We aimed to evaluate minimal hepatic encephalopathy (MHE) with Psychometric Hepatic Encephalopathy (PHES) score and Critical Flicker Frequency (CFF) in alcohol (ALD) and non-alcoholic steatohepatitis related (NASH) related cirrhosis. Methods: 398 patients were screened between March 2016 and December 2018; of which 71 patients were included in ALD group and 69 in NASH group. All included patients underwent psychometric tests which included number connection test A and B (NCT-A and NCT-B), serial dot test (SDT), digit symbol test (DST), line tracing test (LTT) and CFF. MHE was diagnosed when their PHES was

Introduction and aim. Olfactory functions are altered to a variable degree by chronic liver disease. Few studies including only small populations of patients emphasized the possibility of hepatic encephalopathy (HE) influencing olfactory nervous tasks. So far, no study has explicitly focused on olfactory function depending on the severity of HE as assessed by objective diagnostic procedures. Thus we performed a study using the “Sniffin’ Sticks” test system, critical flicker-fusion frequency (CFF) and clinical West Haven criteria.Material and methods. 54 cirrhotic patients with liver cirrhosis were included. Furthermore, 43 adult volunteers participating as a non-cirrhotic control group. Olfactory testing was performed using the “Sniffin’ Stick” test battery (Burghart Medizintechnik, Wedel, Germany) which renders a widely-used tool both in clinical and research settings for the assessment of olfactory threshold, odor identification and discrimination. Several complications of cirrhosis were diagnosed by reference methods. Statistical analysis of cirrhosis-associated complications and their relation to olfactory function was performed. Assessment of HE and classification of different stages were performed according to clinical criteria (West- Haven criteria) and according to CFF, which was determined using a portable analyzer.Results. Olfactory function was significantly reduced in cirrhotic patients (in 61.1%) compared to controls (p < 0.001). Among cirrhotics patients, the prevalence of olfactory deficits (hyposmia, anosmia) increased with the severity of HE as assessed by CFF and clinical criteria (p = 0.008 and p = 0.097, respectively). No correlation was observed between olfactory deficits and severity of liver disease as assessed by Child-Pugh-Score, etiology of cirrhosis and complications of cirrhosis such as ascites and portal venous hypertension.Conclusions. Olfactory testing serves as a screening tool for HE and may faciliate grading of HE-severity.

Background and aims Minimal hepatic encephalopathy (MHE) may impair driving performance and adversely disturbs quality of life. Most drivers with chronic liver disease are not routinely screened for MHE and stay untreated due to the deficiency of standardization of normal values, simple tools, and skills to carry out tests. This study evaluated the usefulness of psychometric tests and critical flicker frequency (CFF) to diagnose MHE among screened drivers with chronic liver disease in Assiut, a city in Upper Egypt. Patients and methods A total of 100 drivers with chronic liver disease were screened for MHE. Routine investigations were carried out for all. Psychometric tests including number connection tests A, symbol digits test and CFF testing were applied for them. mini mental state examination questionnaires and Beck’s inventory were carried out for those diagnosed as having MHE. Results MHE was found among 40%, with 20 (50%) in Child’s A, 11 (27.5%) in Child’s B, and nine (22.5%) in Child’s C cirrhosis (P=0.027), and 45% of those with MHE had bad driving history. Twelve (12%) patients had abnormal psychometric tests. The sensitivity and specificity of receiver operating characteristic curves for CFF in the diagnosis of MHE was 100%, with a cutoff of less than or equal to 38.5 Hz, and the area under the curve was 1.00 (95% confidence interval, 0.964–1.00) (P

Background: Minimal hepatic encephalopathy (MHE) is viewed as mild neuro-cognitive abnormalities in cirrhotics without overt encephalopathy. Diagnostic strategies for MHE include portosystemic encephalopathy (PSE) syndrome test, critical flicker frequency test (CFF), computerised tests like Inhibitory control test, Scan test etc. We compared critical flicker frequency test with standard PSE syndrome test. Methods: Fifty patients with cirrhotics of liver without overt encephalopathy were studied. PSE syndrome test was done with the standard charts. PSE score was calculated from the normal distribution tables. CFF was tested with manual CFF tool. Results: Their mean age (years) was 46 ± 12.8; there were 45 males. Of these 22, 21 and 7 patients belonged to Child's A, B and C categories. PSE score detected MHE in 40%, of which 35% were in Child's A and 65% in Child's B/C. CFF was normal (>39HZ) in 36% patients and abnormal (

Introduction and aims: To determine the prevalence of minimal hepatic encephalopathy(MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE. Materials and methods: We performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment. Results: 64 patients were included. 51.6% were male, the median age was 62 years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8 kPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9 mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24 weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p < 0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p = 0.02), higher Child-Pugh scores at 24-weeks post-treatment (p = 0.04), higher baseline INR levels (1.4 vs. 1.1; p < 0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p = 0.02). During follow-up, those patients without MHE at 24 weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p = 0.04). Conclusion: We found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis. [ABSTRACT FROM AUTHOR]

Background: Minimal hepatic encephalopathy (MHE) is viewed as mild neuro-cognitive abnormalities in cirrhotics without overt encephalopathy. Diagnostic strategies for MHE include portosystemic encephalopathy (PSE) syndrome test, critical flicker frequency test (CFF), computerised tests like Inhibitory control test, Scan test etc. We compared critical flicker frequency test with standard PSE syndrome test. Methods: Fifty patients with cirrhotics of liver without overt encephalopathy were studied. PSE syndrome test was done with the standard charts. PSE score was calculated from the normal distribution tables. CFF was tested with manual CFF tool. Results: Their mean age (years) was 46 ± 12.8; there were 45 males. Of these 22, 21 and 7 patients belonged to Child’s A, B and C categories. PSE score detected MHE in 40%, of which 35% were in Child’s A and 65% in Child’s B/C. CFF was normal (>39HZ) in 36% patients and abnormal (<39HZ) in 64% patients. Mean ammonia levels were significantly higher in abnormal CFF (70.87 ± 14.38) as compared normal CFF (32.21 ± 7.9) group (P < 0.001). The sensitivity of CFF for detecting MHE was 85%, specificity 52%, positive predictive value 56% and negative predictive value 85%. Thus, CFF appears to be a good test for excluding MHE. Conclusions: CFF test is highly sensitive (85%) with high negative predictive value (85%). It is a useful test to rule out MHE. The test is simple, quick and in-expensive and can be performed in the outpatient settings. [ABSTRACT FROM AUTHOR]

A 59-year-old woman had a 1-year history of right vision loss. Her visual acuity was then 0.01 OD, and the critical flicker frequency (CFF) was 8 Hz OD. Goldmann perimetry examination showed inferior suppression of the right visual field center. Funduscopic examination revealed normal coloring of the right optic disc. Imaging studies showed an apical oval tumor. The optic nerve was compressed by both the tumor and the superior rectus muscle/levator palpebrae superioris complex. The tumor was dissected from the surrounding tissues and completely extracted. Histopathologic examination confirmed a cavernous hemangioma. The patient underwent three cycles of postoperative steroid pulse therapy. One year after the surgery, her visual acuity and CFF improved to 1.0 and 32 Hz OD, respectively. Her right visual field was within the normal range.

This study examined the impact of rest breaks on driver fatigue. The study developed and tested a work-rest model to reduce fatigue for chemical truck drivers, following International Labor Organization (ILO) guidelines. The model was tested on a small sample of workers driving from a gas filling plant in Sattahip District, Chonburi Province to Muang District, Samut Sakorn Province. To test the model, data on driver fatigue was assessed using an interview questionnaire and a flicker fusion instrument, and the Z-test was used to compare fatigue among three work-rest patterns. The results showed 24 % of working time (173 min) for the drivers sampled was allocated for relaxation, based on a mean driving time of 12 h. Two work-rest models were developed, considering driving distance, time and levels of fatigue. The findings indicated that the regular schedule pattern resulted in the highest levels of fatigue, both as measured by subjective questionnaire and objectively by the critical flicker frequency value (CFF). Model II, with two 26-min rest breaks, offers a more effective model to reduce fatigue, using less driving time than model I, with four 13-min rest breaks. However, this resulted in other new challenges, for example, the need for extended shifts, an increase in production costs and personal costs. Transportation business owners should prepare meals and drinks for chemical transport drivers on the Sattahip to Samut Sakorn route (and other cross-province routes) in order to make it more convenient for them to follow safety practices.

Alpha oscillations are particularly important in determining our percepts and have been implicated in fundamental brain functions. Oscillatory activity can be spontaneous or stimulus‐related. Furthermore, stimulus‐related responses can be phase‐ or non‐phase‐locked to the stimulus. Non‐phase‐locked (induced) activity can be identified as the average amplitude changes in response to a stimulation, while phase‐locked activity can be measured via reverse‐correlation techniques (echo function). However, the mechanisms and the functional roles of these oscillations are far from clear. Here, we investigated the effect of ambient luminance changes, known to dramatically modulate neural oscillations, on spontaneous and stimulus‐related alpha. We investigated the effect of ambient luminance on EEG alpha during spontaneous human brain activity at rest (experiment 1) and during visual stimulation (experiment 2). Results show that spontaneous alpha amplitude increased by decreasing ambient luminance, while alpha frequency remained unaffected. In the second experiment, we found that under low‐luminance viewing, the stimulus‐related alpha amplitude was lower, and its frequency was slightly faster. These effects were evident in the phase‐locked part of the alpha response (echo function), but weaker or absent in the induced (non‐phase‐locked) alpha responses. Finally, we explored the possible behavioural correlates of these modulations in a monocular critical flicker frequency task (experiment 3), finding that dark adaptation in the left eye decreased the temporal threshold of the right eye. Overall, we found that ambient luminance changes impact differently on spontaneous and stimulus‐related alpha expression. We suggest that stimulus‐related alpha activity is crucial in determining human temporal segmentation abilities. By manipulating ambient luminance viewing conditions, we show the impact of luminance changes on alpha oscillatory properties of human electroencephalogram (spontaneous and stimulus‐related activity), and on our visual temporal segmentation abilities with a monocular critical‐flicker fusion task. Results suggest that the visual system adapts its oscillatory alpha dynamics to fit the environmental light conditions. [ABSTRACT FROM AUTHOR]

Introduction and aim. Olfactory functions are altered to a variable degree by chronic liver disease. Few studies including only small populations of patients emphasized the possibility of hepatic encephalopathy (HE) influencing olfactory nervous tasks. So far, no study has explicitly focused on olfactory function depending on the severity of HE as assessed by objective diagnostic procedures. Thus we performed a study using the "Sniffin' Sticks" test system, critical flicker-fusion frequency (CFF) and clinical West Haven criteria. Material and methods. 54 cirrhotic patients with liver cirrhosis were included. Furthermore, 43 adult volunteers participating as a non-cirrhotic control group. Olfactory testing was performed using the "Sniffin' Stick" test battery (Burghart Medizintechnik, Wedel, Germany) which renders a widely-used tool both in clinical and research settings for the assessment of olfactory threshold, odor identification and discrimination. Several complications of cirrhosis were diagnosed by reference methods. Statistical analysis of cirrhosis-associated complications and their relation to olfactory function was performed. Assessment of HE and classification of different stages were performed according to clinical criteria (West-Haven criteria) and according to CFF, which was determined using a portable analyzer. Results. Olfactory function was significantly reduced in cirrhotic patients (in 61.1%) compared to controls (p < 0.001). Among cirrhotics patients, the prevalence of olfactory deficits (hyposmia, anosmia) increased with the severity of HE as assessed by CFF and clinical criteria (p = 0.008 and p = 0.097, respectively). No correlation was observed between olfactory deficits and severity of liver disease as assessed by Child-Pugh-Score, etiology of cirrhosis and complications of cirrhosis such as ascites and portal venous hypertension. Conclusions. Olfactory testing serves as a screening tool for HE and may faciliate grading of HE-severity. [ABSTRACT FROM AUTHOR]

In patient with cirrhosis, minimal hepatic encephalopathy (MHE) is defined by the presence of neuropsychological abnormalities detectable by psychometric or neuropsychological tests without any clinical sign of hepatic encephalopathy. Its frequency is high, affecting between 20 and 60% of hospitalized cirrhotic patients. MHE is predictive of the occurrence of clinical hepatic encephalopathy, is a factor of poor prognosis and is associated with higher mortality. MHE also impacts everyday life by increasing traffic and household accidents. Diagnostic methods are complex, require time and a trained practitioner which explains the low screening rate despite the existence of effective therapies. [ABSTRACT FROM AUTHOR]

Background: Minimal hepatic encephalopathy (MHE) is viewed as mild neuro-cognitive abnormalities in cirrhotics without overt encephalopathy. Diagnostic strategies for MHE include portosystemic encephalopathy (PSE) syndrome test, critical flicker frequency test (CFF), computerised tests like Inhibitory control test, Scan test etc. We compared critical flicker frequency test with standard PSE syndrome test. Methods: Fifty patients with cirrhotics of liver without overt encephalopathy were studied. PSE syndrome test was done with the standard charts. PSE score was calculated from the normal distribution tables. CFF was tested with manual CFF tool. Results: Their mean age (years) was 46 ± 12.8; there were 45 males. Of these 22, 21 and 7 patients belonged to Child's A, B and C categories. PSE score detected MHE in 40%, of which 35% were in Child's A and 65% in Child's B/C. CFF was normal (>39HZ) in 36% patients and abnormal (<39HZ) in 64% patients. Mean ammonia levels were significantly higher in abnormal CFF (70.87 ± 14.38) as compared normal CFF (32.21 ± 7.9) group (P < 0.001). The sensitivity of CFF for detecting MHE was 85%, specificity 52%, positive predictive value 56% and negative predictive value 85%. Thus, CFF appears to be a good test for excluding MHE. Conclusions: CFF test is highly sensitive (85%) with high negative predictive value (85%). It is a useful test to rule out MHE. The test is simple, quick and in-expensive and can be performed in the outpatient settings. [ABSTRACT FROM AUTHOR]

This study aimed to compare the critical flicker frequency ( CFF) and the mail-in cognitive function screening ınstrument ( MCFSI) tests' effectiveness in diagnosing neurocognitive function losses in patients having severe obstructive sleep apnea syndrome ( OSAS). A total of 85 subjects (47 patients with a diagnosis of severe OSAS and 38 healthy controls) were included into the study. MCFSI scores greater than or equal to five and CFF scores less than 39 Hz were considered abnormal. Demographic and polysomnographic parameters of patients with OSAS were studied, and correlations between the MCFSI, CFF scores and Epworth Sleepiness Scale ( ESS) scores were analysed. The mean age of the patients was 49.6 ± 12.0 years. In the OSAS group, the CFF score was found to be low when compared with the control group, while the MCFSI score was found to be high. Pathological CFF scores (<39) were found in 13 patients (27.7%) in the OSAS group, while pathological MCFSI scores (≥5) were found in 19 patients (40.4%). CFF scores were found to be low in only 26% of the patients with OSAS who were found to have high MCFSI scores. MCFSI scores were high in only 38% of the patients with OSAS who were found to have low CFF scores. There was a significant correlation between ESS and CFF scores. In conclusion, the usefulness of the CFF test in determining cognitive function loss in patients with OSAS needs to be demonstrated via studies which utilize a larger sample size. [ABSTRACT FROM AUTHOR]

Objective: To assess critical flicker frequency (CFF) in normal uneventful pregnancy and preeclampsia.Study-design: Case-control observational study at the University Hospital Jena and Outpatient Institute for Prenatal Diagnosis and Preventive Medicine. 25 non-pregnant women, 75 uncomplicated pregnant women in first, second and third trimester, and 15 women with overt preeclampsia. For comparison with preeclamptic patients we matched 15 normal pregnant women (mNP) for age, parity, body mass index, current smoking and family history of cardiovascular disease (CVD). We measured CFF using the portable HEPAtonorm Analyzer (nevoLAB GmbH, Germany). This device generates a flickering red light, starting with a frequency of 60Hz, giving the subjective an impression of a steady light. The participant signifies once the impression of a flickering light is recognized, and this CFF is recorded. Mean CFF and standard deviation is automatically calculated. Statistical analysis was performed using SPSS Version 22 for Windows. Following assessment of normal distribution with Kolmogorov-Smirnow test, comparisons were made with univariate and multivariate ANOVA and with unpaired and paired t test for continuous data and with χ2 test for categorical data.Results: Critical flicker frequency in healthy pregnant women does not differ from nonpregnant women. No significant differences in CFF measurements exist in first, second, and third trimester. In preeclampsia, CFF is significantly decreased compared to normal pregnant women (PE 38.80±2.16 vs. mNP 46.23±3.37; p=0.000). This alteration persists even some weeks postpartum (PE 41.17±1.13 vs. mNP 46.45±3.44; p=0.003).Conclusion: In preeclamptic women, CFF is decreased indicating an altered endothelial situation. The finding that CFF remains reduced postpartum may be explained by either the effect of preeclampsia on maternal endothelium causing longer lasting damage or indicate a preexisting endothelial disorder. Up to this point, precise responsible mechanisms for altered CFF in preeclampsia are currently unclear and further studies are needed. [ABSTRACT FROM AUTHOR]

Introduction. Blood ammonia-measurements are often performed in the emergency departments to diagnose or rule out hepatic encephalopathy (HE). However, the utility and correct interpretation of ammonia levels is a matter of discussion. At this end the present prospective study evaluated whether blood ammonia levels coincide with HE which was also established by the West Haven criteria and the critical flicker frequency, respectively.Material and methods. In 59 patients with known cirrhosis ammonia-levels were determined and patient were additionally categorized by the West-Haven criteria and were also evaluated psychophysiologically using the critical flicker frequency, CFF for the presence of HE.Results. When false positive and false negative results were collapsed the determination of blood ammonia levels alone resulted in 40.7% in a misdiagnoses of HE compared to the West-Haven criteria (24/59 when using West-Haven criteria, 95% confidence interval [CI], 28.1% to 54.3%) and 49.2% when compared with the results of the CFF (29/59, when using CFF, 95% CI, 35.9% to 62.5%).Discussion. Ammonia blood levels do not reliably detect HE and the determination of blood ammonia can not be regarded a useful screening test for HE. Its use as sole indicator for a HE in the Emergency Department may frequently result in frequent misinterpretations.

Background/Aim: Minimal hepatic encephalopathy (MHE) impairs health-related quality of life and driving ability of the patient. Objective: We assessed the utility of the inhibitory control test (ICT), critical flicker frequency (CFF), and psychometry in the diagnosis of MHE. Patients and Methods: Consecutive patients with cirrhosis underwent number connection tests A and B (NCT-A, B), digit symbol test (DST), line tracing test (LTT), serial dot test (SDT), CFF, and ICT at baseline and after four hours. Fifty healthy subjects served as controls for the ICT test. Results: Fifty patients with cirrhosis (43.4 ± 10.2 yrs, M: F 42:8) underwent psychometric tests [NCT-A (48.3 ± 17.7 vs. 42.6 ± 17.3 sec, P = 0.001), NCT-B (85.7 ± 40.1 vs. 90.2 ± 37.0 sec, P = 0.18), DST (23.5 ± 9.3 vs. 23.0 ± 8.7, P = 0.45), LTT (96.6 ± 48.2 vs. 96.8 ± 46.8 sec, P = 0.92), SDT (88.0 ± 39.5 vs. 83.4 ± 37.2 sec, P = 0.02)] at baseline and after four hours. Target accuracy of ICT was lower in patients with cirrhosis compared with controls (88.4 ± 5.6 vs. 95.6 ± 2.1, P = 0.01), whereas ICT lures were higher (18.3 ± 4.2 vs 10.2 ± 2.8, P = 0.01). Patients with cirrhosis showed a reduction in lures in the second evaluation compared with the first (18.3 ± 4.2 vs. 17.1 ± 4.3, P = 0.003) but no change in target accuracy (88.4 ± 5.6 vs. 88.4 ± 5.3, P = 0.97). Control subjects did not show any change either in lures (10.2 ± 2.8 vs. 10.3 ± 2.1, P = 0.65) or target accuracy (95.6 ± 2.1 vs. 95.5 ± 2.2, P = 0.82). The sensitivity and specificity of ICT test for the diagnosis of MHE at lure rate >16.5 was 88.5 and 56%, respectively. CFF in patients with MHE (38.4 ± 1.8 vs. 38.6 ± 1.5, P = 0.3) and non MHE (40.6 ± 2.2 vs. 40.8 ± 2.2, P = 0.6) did not show any difference after four hours as in controls (41.9 ± 2.4 vs. 42.1 ± 2.0, P = 0.3). Thirty one (31%) patients preferred psychometric tests, 57 (57%) preferred CFF and only 12 (12%) preferred ICT ( P = 0.001). Conclusions: ICT, CFF, and psychometric tests are useful tools to assess MHE, and CFF was preferred by this study cohort.

Purpose: Developing a method to improve the accuracy of the measuring of critical flicker frequency (CFF).Methods: When measuring CFF the light pulses with LEDs yellow 5 mm in diameter with a force of light 3 mcd placed in an area near point of clear vision. Formation of light pulses and measuring CFF was performed using PC Pentium III by the method of successive approximation. Measured CFF value was noted on the plane in the coordinates «CFF value — the number of measurement», a graph of CFF values was drawn as a function F = f (Ni), where Ni — number of i-th measurement, i = 1, 2,…, k, k — number of measurements to obtain a quasi-stationary mode when the transition process is completed. In the quasi-stationary mode we were performed a specified number of measurements and then calculated the CFF estimate as the mean value of test results obtained in the quasi-stationary mode.Results: Reducing the random component of the CFF measurement error of study group of 10 pre-trained subjects was received in 8 of them and varies from 31.3 to 78.6 %.Conclusion: Analyzing the dynamics of CFF values obtained during its measurement and performing a statistical analysis of the measurements obtained in the quasi-stationary mode, we can improve the accuracy of CFF estimate.

Background & Aims: Hepatic encephalopathy (HE) is a frequent and severe complication in patients after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, risk factors for post-TIPS HE remain poorly defined. Minimal HE (mHE) is a well-known risk factor for overt HE in patients with cirrhosis without TIPS. We aimed to evaluate three tools frequently used for diagnosing mHE for their dynamic changes and their predictive value for overt HE after TIPS., Methods: We prospectively recruited 84 consecutive patients before TIPS insertion and monitored them for 180 days for post-TIPS HE. Before TIPS insertion, the patients underwent the portosystemic encephalopathy (PSE) syndrome test, the animal naming test (ANT), and the critical flicker frequency (CFF). Patients were retested after TIPS insertion., Results: The majority of patients were male (67.9%), and the predominant indication for TIPS was refractory ascites (75%). Median age was 59 years, model for end-stage liver disease score was 12, and 66.3%, 64.6%, and 28.4% patients had evidence for mHE according to the PSE syndrome test, ANT, and CFF, respectively. Overall, 25 patients developed post-TIPS HE within 180 days after TIPS insertion. Post-TIPS incidence of overt HE was 22.2, 28.6, 45.5, and 55.6% in those with no, one, two, and three pathological tests at baseline, respectively. However, none of the three tests was significantly associated with post-TIPS HE. Of note, mean performance in all tests remained stable over time after TIPS insertion., Conclusions: PSE syndrome test, ANT and CFF, which are frequently used for diagnosing mHE have limited value for predicting HE after TIPS insertion. We could not find evidence that TIPS insertion leads to a psychometric decline in the long term., Impact and Implications: This prospective observational study compared three diagnostic tests for mHE and showed the limited value of these tests for predicting overt HE in patients with cirrhosis undergoing TIPS insertion. In addition, the results suggest that cognitive performance generally remains stable after TIPS insertion. These results are important for physicians and researchers involved in the management of patients with cirrhosis undergoing TIPS procedures. The study's findings serve as a starting point for further investigations on the development of more effective strategies for predicting and managing post-TIPS HE., Clinical Trial Number: ClinicalTrials.gov NCT04801290., Competing Interests: KW has taken part in the development of the Psychometric Hepatic Encephalopathy Score (PHES), and the copyright of this test is held by Hannover Medical School. BM received lecture fees from Norgine. HW received fees from Falk, Intercept, Norgine, and Pfizer. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)