Date Published: February 1, 2017
Publisher: Public Library of Science
Author(s): Carla Giménez-Garzó, Juan José Garcés, Amparo Urios, Alba Mangas-Losada, Raquel García-García, Olga González-López, Remedios Giner-Durán, Desamparados Escudero-García, Miguel Angel Serra, Emilio Soria, Vicente Felipo, Carmina Montoliu, Han-Chieh Lin.
The psychometric hepatic encephalopathy score (PHES) is the “gold standard” for minimal hepatic encephalopathy (MHE) diagnosis. Some reports suggest that some cirrhotic patients “without” MHE according to PHES show neurological deficits and other reports that neurological alterations are not homogeneous in all cirrhotic patients. This work aimed to assess whether: 1) a relevant proportion of cirrhotic patients show neurological deficits not detected by PHES; 2) cirrhotic patients with mild neurological deficits are a homogeneous population or may be classified in sub-groups according to specific deficits.
Cirrhotic patients “without” (n = 56) or “with” MHE (n = 41) according to PHES and controls (n = 52) performed psychometric tests assessing attention, concentration, mental processing speed, working memory and bimanual and visuomotor coordination. Heterogeneity of neurological alterations was analysed using Hierarchical Clustering Analysis.
PHES classified as “with” MHE 42% of patients. Around 40% of patients “without” MHE according to PHES fail two psychometric tests. Oral SDMT, d2, bimanual and visuo-motor coordination tests are failed by 54, 51, 51 and 43% of patients, respectively. The earliest neurological alterations are different for different patients. Hierarchical clustering analysis shows that patients “without” MHE according to PHES may be classified in clusters according to the tests failed. In some patients coordination impairment appear before cognitive impairment while in others concentration and attention deficits appear before.
PHES is not sensitive enough to detect early neurological alterations in a relevant proportion of cirrhotic patients. Oral SDMT, d2 and bimanual and visuo-motor coordination tests are more sensitive. The earliest neurological alterations are different in different cirrhotic patients. These data also have relevant clinical implications. Patients classified as “without MHE” by PHES belonging to clusters 3 and 4 in our study have a high risk of suffering clinical complications, including overt HE and must be diagnosed and clinically followed.
Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome present in patients with chronic liver diseases that leads to alterations in personality, sleep, cognitive function, motor activity and coordination and level of consciousness and may lead to coma and death [1–2]. Around 33%-50% of cirrhotic patients without clinical symptoms of HE show minimal hepatic encephalopathy (MHE), which can be unveiled using psychometric tests or neurophysiological analysis [2–5]. MHE reduces quality of life and life span and is associated with increased risk of work, driving, and home accidents and predisposes to clinical HE [6–11]. Patients with MHE show mild cognitive impairment, attention deficits [12–17] and impaired visuo-motor and bimanual coordination [18–19].
The different tests and subtests performed provide, in addition to the PHES scores, 20 additional scores for parameters measuring different aspects of cognitive and motor function. These scores for cirrhotic patients classified as “without” or “with” MHE according to PHES and of controls are given in Table 2 (PHES scores) and Table 3 (all other scores). After applying Exploratory Data Analysis, the scores for PHES, critical flicker frequency and for 10 of these parameters (named tests for simplicity from now on) were selected to compare performance of patients “without” or “with” MHE and controls. The results are summarized in Fig 1.
This report provides the following relevant findings:
In summary, the results reported show that the PHES is not sensitive enough to detect the earliest neurological deficits in cirrhotic patients. The use of more sensitive tests such as oral SDMT and bimanual coordination would increase the number of subjects diagnosed of MHE by around 60%. This would allow earliest detection and treatment of MHE and improving quality of life. It is also shown that cirrhotic patients are a heterogeneous population concerning their earliest neurological alterations, likely due to initial alterations in different cerebral mechanisms. Also, patients classified as “without MHE” by PHES belonging to clusters 3 and 4 in our study have a high risk of suffering clinical complications, including overt HE and must be diagnosed and clinically followed. This further supports the need for the use of a combination of sensitive tests to diagnose MHE.