Patients With Minimal Hepatic Encephalopathy Have Poor Insight Into Their Driving Skills

Transcription

1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2008;6: Patients With Minimal Hepatic Encephalopathy Have Poor Insight Into Their Driving Skills JASMOHAN S. BAJAJ,* KIA SAEIAN, MUHAMMAD HAFEEZULLAH, RAYMOND G. HOFFMANN, and THOMAS A. HAMMEKE *Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia; Division of Gastroenterology and Hepatology, Department of Biostatistics, Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin See Mardini H et al and Bajaj JS et al in the December 2008 issue of Gastroenterology. See CME exam on page Background & Aims: Minimal hepatic encephalopathy (MHE) is associated with impaired driving skills. It is not clear whether patients have insight into this. The Driving Behavior Survey (DBS) is a validated self- or observeradministered questionnaire. DBS consists of a total score (maximum, 104) and an attention-related driving skills section (maximum, 40). DBS was used to compare self-assessment with observer-assessment of driving skills in cirrhotic patients tested for MHE. Methods: Forty-seven nonalcoholic cirrhotic patients and 40 controls underwent psychometric tests, DBS, and driving simulation with navigation/ driving tasks. An adult familiar with the subject s driving completed the DBS independently. Simulator performances, total DBS scores, and driving skill scores were compared between/within groups (MHE, MHE, and controls) with respect to self-assessment and observer assessment. Results: Thirty-six patients were MHE and 11 were MHE. MHE had a significantly higher simulator crash (MHE, 3;MHE, 1.2; controls, 1.7; P.001) and illegal turn rate (MHE, 1.2; MHE, 0.3; controls, 0.1; P.0001). Despite this worse performance, MHE patients rated themselves similar to MHE patients and control groups on total (P.28) and driving skills scores (P.19). Observer assessment in MHE was significantly lower for total (P.0001) and driving skills (P.0001) compared with observer assessment for MHE patients and control groups. MHE patients were rated significantly lower on driving skills (34 vs 37; P.02) and trended lower in the total score (P.08) by observers compared with self-ratings. In contrast, MHE and control groups rated themselves similar to their observers on driving skills and total DBS scores. Conclusions: MHE patients have poor insight into their driving skills. A part of the MHE patient s clinical interview should be to increase awareness of this driving impairment. Minimal hepatic encephalopathy (MHE) is a significant neurocognitive complication of cirrhosis. 1,2 It is present in up to 80% of patients tested, it is associated with a poor quality of life, and it is associated with increased progression to overt hepatic encephalopathy. 3 5 Importantly, MHE also is associated with driving behavior impairment. 6 8 Driving difficulties in patients with MHE can stem from deficiencies in several components, including impaired reaction times, psychomotor slowing, and navigation skill disturbances. 9,10 A recent study showed a higher risk of traffic violations and motor vehicle accidents in patients with MHE. 11 Insight into or self-awareness of driving impairment is essential for patients to seek intervention. Because patients with MHE have no specific symptoms, it is important that factors that could prevent adverse driving outcomes such as traffic accidents be studied by the physician and the validity of the patient s self-report of driving adequacy be examined in detail. 1 The Driving Behavior Survey (DBS) is a 26-item scale that has been validated by Barkley et al 12 in children and adults with attention deficit hyperactivity disorder (ADHD). This questionnaire was chosen because both MHE and ADHD patients struggle with attention problems and also show driving impairment. It has been studied in MHE and previously was called the Driving Behavior Questionnaire. 12 Each question is rated on a scale of 1 to 4 (maximum score, 104). Items on the DBS inquire about both driving skills that can be readily affected by impairment in attention, vigilance, and safety judgments (10 items collectively referred to here as driving skills; eg, reacts quickly and properly to brake lights when activated on vehicles ahead ) as well as items that relate to long-standing driving habits (16 items) (eg, refers to maps before driving through a new area or city ). In addition to the total scores, this research investigated the self-assessment and observer-assessment of driving skills. Higher scores indicate better driving. The hypothesis of the study was that patients with MHE have impaired insight into their driving behavior. The aims were first to determine whether patients with MHE, a group already known to make more errors in driving, accurately characterize their driving behavior when compared with measures of their driving skills and ratings of their driving from observers, and, second, to determine whether impaired insight in MHE is identified best by items on the DBS that are thought to be most affected by an encephalopathic state (driving skills assessment). Methods Consecutive nonalcoholic patients with cirrhosis who were car drivers and were tested for MHE were included. 13 Cirrhotic patients on psychoactive drugs (including psychiatric and seizure medications, ADHD therapy, and interferon), those Abbreviations used in this paper: ADHD, attention deficit hyperactivity disorder; DBS, Driving Behavior Survey; MHE, minimal hepatic encephalopathy by the AGA Institute /08/$34.00 doi: /j.cgh

2 1136 BAJAJ ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 10 who had consumed alcohol within the past 6 months, and those on treatment for overt hepatic encephalopathy were excluded. Alcohol use history was corroborated by relatives and in the medical chart using serum alcohol levels at several points during the medical evaluation. Patients underwent a detailed physical examination to exclude overt hepatic encephalopathy. After this they underwent a psychometric battery consisting of the number connection test-a, the number connection test-b, block design test, and digit symbol test components of the Wechsler s adult intelligence scale-iii. 6,14 MHE was diagnosed if any 2 of these tests were impaired 2 SDs beyond age- and education-matched community controls. 6 The inhibitory control test, a test of response inhibition, with 90% sensitivity and specificity for the diagnosis of MHE, also was administered to all subjects during the same sitting. 15 A group of age- and education-matched healthy community controls, who were recruited through community advertisements, also underwent the same testing. Written informed consent was obtained from each subject. All subjects were paid for their participation. The DBS then was administered to all subjects and they also were asked to provide the contact information for an adult familiar with their driving habits. This adult, who was blinded to the patient s MHE status, then was contacted in the subject s absence. After confirming that the observer was familiar with the subject s driving, the DBS was administered to them by telephone interview to judge the research subject s driving habits. All participants (cirrhotic patients and controls) underwent driving simulation using a STISIM simulator, which has been studied in patients with MHE and consists of training, navigation, and driving tasks (Systems Technology Inc, Hawthorne, CA; technology in the model BR1100, Beta Research, Inc, Los Gatos, CA). 13 The training session lasted for 15 minutes and familiarized the subjects with the driving simulator. The navigation task consisted of driving on a fixed path while consulting a map on the simulator. Illegal turns, defined as turns away from the marked path on the map, and collisions during this task were the outcome. The driving task consisted of driving on a path that ranged from hilly terrain to city driving under optimum weather conditions. The number of collisions was the end point for this portion of the study. 13 The Institutional Review Board at the Medical College of Wisconsin approved this protocol. Statistical Analysis Diagnosis of MHE was made based on predetermined criteria in our population, which meant any 2 of the following criteria 6,15 : number connection test-a, greater than 34 seconds; number connection test-b, greater than 99 seconds; block design test, less than 31 raw score; or digit symbol test, less than 71 raw score. Analysis. Cirrhotic patients were divided into those with MHE (MHE ) and without MHE (MHE ), and were compared with controls with respect to demographics, selfassessment and observer assessment of DBS total and driving skill components, and driving simulation outcomes. Student t tests were used to compare continuous variables across groups and paired t tests were used to compare selfassessment and observer assessment of DBS total and driving skills within groups. Differences between self-assessment and observer assessment (obtained by subtracting the observer score from the self-score of the total DBS and driving skills component of the DBS) across MHE, MHE, and control groups were calculated and compared using multiple comparisons adjusted t tests on the differences after a one-way analysis of variance. Results are expressed as mean SD unless otherwise specified. Results Seventy-four cirrhotic patients and 74 controls were approached; 6 patients with cirrhosis refused to participate. A total of 68 cirrhotic patients and 74 controls underwent psychometric testing, self-assessment of DBS, and driving simulation. The observers, whose information was provided by the subjects, could be contacted in only 47 cirrhotic patients and 40 controls, who then were included in the final study. Of the 21 cirrhotic patients whose observers could not be contacted, 14 were MHE and 7 were MHE. There were 29 cirrhotic patients with hepatitis C, 5 had both hepatitis C and alcoholic liver disease (without alcohol intake within 6 months documented through personal interviews and through chart review), 5 with autoimmune hepatitis, 3 with primary sclerosing cholangitis, 1 with primary biliary cirrhosis, and 1 with cryptogenic cirrhosis. Based on the psychometric tests, 36 cirrhotic patients had MHE and the remaining 11 were MHE. There was no significant difference in Child status, serum creatinine level, bilirubin level, and international normalized ratio between groups (Table 1). Two MHE and 1 MHE patient were on the waiting list for transplant. Observers. Most observers were spouses (MHE, 61%; MHE, 55%; and controls, 55%; P.6), and the remaining observers were close friends (MHE, 17%; MHE, 27%; and controls, 23%; P.2) or first-degree relatives (MHE, 22%; MHE, 18%; and controls, 12%; P.2) who were familiar with the subject s driving. Minimal hepatic encephalopathy group, minimal hepatic encephalopathy group, and control group comparison. There was no significant difference in the demographic characteristics and driving history between the groups. On the other hand, MHE patients had a significantly worse psychometric performance and higher rate of collisions (both in driving and navigation task) and illegal turns on the driving simulator compared to controls and MHE patients (Table 1). Comparison between the minimal hepatic encephalopathy negative group and controls. There was no significant difference between controls and the MHE group with respect to demographics and psychometric test performance. There was no significant difference in the number of collisions (P.1) and illegal turns (P.3) on the simulator between MHE patients and controls (Table 1). Self-report of driving abilities (Driving Behavior Survey). There was no significant difference between MHE, MHE, and control groups in self-assessment of driving abilities as reflected by total DBS scores or the driving skills scores (Table 2). Observer versus self-ratings of driving abilities. Observers rated MHE patients significantly lower on the driving skills compared with the subjects self-evaluation. There was a trend towards a lower observer versus self-report for the total DBS score. In contrast, there was no significant difference between self-assessment and observer assessment on the total

3 October 2008 POOR INSIGHT IN MHE 1137 Table 1. Demographic, Psychometric, and Driving Simulator Performance MHE (n 36) MHE (n 11) Controls (n 40) P value among groups Age, y Sex, male/female 21/15 6/5 25/15.9 Child class, A/B/C 32/4/0 9/2/0.6 Serum creatinine level, mg/dl International normalized ratio Serum bilirubin level Driving experience, y NCT-A, s NCT-B, s DST, raw score BDT, raw score ICT lures Simulator driving task collisions Simulator navigation task collisions Simulator illegal turns NOTE. No significant difference in age, sex, Child class, serum variables of Model for End-stage Liver Disease (MELD) score, and driving experience was noted between groups. A significantly impaired performance on the driving simulator and ICT was observed in the MHE group. Serum values for controls were not drawn. NCT-A, number connection test-a; NCT-B, number connection test-b; DST, digit symbol test; BDT, block design test; ICT, inhibitory control test. DBS or the driving skills in the MHE or the control groups (Table 2). Comparison of observer Driving Behavior Survey assessment between groups. MHE patients were assessed significantly lower on their total DBS and driving skills component by their raters compared with the ratings in the MHE and control groups (Table 2). Comparison of differences in self-scores and observer scores between groups. There was a significantly greater difference between self-ratings and observer ratings of the total DBS score in MHE patients ( [SE]) compared with MHE patients ( [SE]) and controls ( [SE]; P.03). Similarly, the difference between self-assessment and observer assessment of the driving skills component was higher in MHE patients (2 0.9 [SE]) compared with MHE patients ( [SE]) and controls ( [SE]; P.04) (Figure 1). Discussion The current study shows that patients with MHE rate themselves equivalent to controls and cirrhotic patients without MHE despite having a significantly worse driving performance. Also, observers rate MHE patients as poorer drivers compared with MHE patients or controls. These findings indicate that MHE patients have poor insight into their driving deficiencies. These results show that this poor insight is evident despite a significantly higher collision and illegal turn rate on the driving simulator. MHE patients rated themselves equivalent to controls and MHE patients on the total DBS score as well as driving skill assessment. Observers familiar with their driving skills rated MHE patients significantly lower than the patients self-rating. Moreover, observer assessment of total DBS and driving skills component in MHE patients was significantly lower compared with the observer assessment of MHE and control groups. The difference between self-assessment and observer assessment also was significantly higher in the MHE group compared with the MHE and control groups. MHE has been associated with difficulty in driving and a high risk of traffic accidents and violations Proposed reasons for this driving difficulty include impaired reaction times, decreased visuomotor coordination, and navigation problems. 9,10,13 This multidimensional driving impairment requires continued investigation and definition because traffic accidents Table 2. DBS Comparison Within and Between Groups MHE (n 36) MHE (n 11) Controls (n 40) P value among groups P value of comparison between self-assessment and observer assessment MHE MHE Controls Total DBS: self-assessment (maximum, 104) Total DBS: observer assessment (maximum, 104) Driving skills: self-assessment (maximum, 40) Driving skills: observer assessment (maximum, 40) NOTE. A significantly lower observer assessment of driving skills in MHE group compared with self-assessment was noted. Observer assessment of total DBS and driving skills was significantly lower in the MHE group compared with the observer assessment in MHE and control groups.

4 1138 BAJAJ ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 10 Figure 1. Difference between MHE, MHE, and controls self-assessment and observer assessment of total DBS and driving skills component showed that there was a significantly higher difference between the self-ratings and observer ratings in MHE compared with MHE patients and controls. are a leading cause of morbidity and mortality in the United States. 16 Because patients with MHE have no symptoms, evaluation of self-awareness in MHE patients can be challenging in this group. 1,2,17,18 However, the manifestations of poor driving skills are evident from the higher number of traffic accidents and violations that MHE patients experienced in the simulator and in real life. 11,13 Therefore, the importance of specifically inquiring about the driving history in patients with cirrhosis would help create awareness in the patient and hopefully help the development of insight into this issue. In addition, education of patients and relatives regarding the driving impairments in MHE also would be helpful in raising self-awareness about driving practices. Recent literature has highlighted the negative impact of cirrhosis on survival after trauma and traffic accidents This further accentuates the risk that MHE drivers face while driving. Therefore, it follows that an objective evaluation, such as a driving history and corroboration from relatives in patients with cirrhosis, would identify individuals at a particularly high risk of poor driving outcomes. Corroboration from relatives has been used to confirm alcohol use in patients with cirrhosis. 22 This should be extended to driving behavior as well because this study shows that adult observers are acutely observant of driving impairments. Similar to MHE patients, patients with ADHD suffer from attention deficits. 23 ADHD patients also have several driving impairments and difficulties with psychometric function, which is why the DBS, which has been studied in ADHD, was chosen for this study. 12,23,24 Parents assessing their children with ADHD using the DBS rated the children s driving skills significantly lower than those who did not have ADHD. 12 Patients with ADHD are decidedly younger than most patients with cirrhosis and are actively seeking medical attention for problems related to inattentiveness. In addition, the age range of most ADHD patients is associated with a high risk of traffic accidents and violations even without the compounding deleterious effect of ADHD. 23 On the other hand, MHE patients are older than ADHD patients. The patients in the current study population are in the age range of the safest age group of any population with respect to traffic violations and accidents. Thus, driving assessment differences are likely to be more subtle than those expected in ADHD. Parents assessing children for whom they are seeking treatment are also likely to rate them differently compared with assessment of adult raters of a patient (with MHE) who has not sought medical attention for that condition. Vested interests, such as a spouse protecting their partners ability to drive by falsely rating them higher, also would be expected to play a key role in that assessment. Because subjects were free to provide the contact information of an observer of their choice, it may be possible that these vested interests would dictate the choice of the observer, that is, subjects would probably name an observer who would be likely to give a favorable assessment of their driving. Despite these complicating factors, observers rated MHE patients much lower with respect to their driving skills compared with their self-assessment. There was also a trend towards lower total DBS scores in observers compared with self-assessment in the MHE group. In sharp contrast, there was no significant difference in the driving skills rating or total DBS score between self and observer assessment in the group without MHE and controls. Insight into a disease state is one of the most significant forces that can spur patients to seek health care. 25 Absence of insight or poor insight can hinder acknowledgment of the disease process and interfere with potential recognition and treatment. The trans-theoretical model of health behavior change also suggests that patients with MHE and driving difficulties may be in the pre-contemplation stage of change. 25 This stage is characterized by an unwillingness to recognize a problem either because the patient is unaware of the problem or believes that they will be unable to change their behavior. 25 Because of their lack of personal insight into their driving skills, MHE patients are not aware of their driving impairment. Anosognosia or attenuated awareness of sensory and cognitive deficits has been noted in several diseases such as Alzheimer s disease, schizophrenia, and traumatic brain injury It has been associated with a worse prognosis and dangerous behaviors in Alzheimer s disease. 26,29 One study showed that one third of patients with Alzheimer s disease who failed a driving test still considered themselves safe drivers. 30 Anosognosia in overt hepatic encephalopathy is evident because relatives are often the first to notice changes in behavior and bring them to medical attention. 31 In contrast, MHE patients by definition have no specific symptoms. 1 We suggest that, similar to their lack of awareness of the driving deficits, the lack of awareness of attention deficits and psychomotor slowing represents a core symptom of MHE patients and underlies their diminished appreciation of driving deficits. In summary, patients with MHE have poor insight into their driving skills. Because of this, an objective driving history, corroboration with relatives, and education of patients, relatives, and caregivers regarding driving practices should be completed as part of the clinical interview. This would increase the patient s self-awareness of the driving impairment and increase the implementation of appropriate therapy in MHE patients.

5 October 2008 POOR INSIGHT IN MHE 1139 References 1. Ortiz M, Jacas C, Cordoba J. Minimal hepatic encephalopathy: diagnosis, clinical significance and recommendations. J Hepatol 2005;42(Suppl):S45 S Qadri AM, Ogunwale BO, Mullen KD. Can we ignore minimal hepatic encephalopathy any longer? Hepatology 2007;45: Arguedas MR, DeLawrence TG, McGuire BM. Influence of hepatic encephalopathy on health-related quality of life in patients with cirrhosis. Dig Dis Sci 2003;48: Romero-Gomez M, Boza F, Garcia-Valdecasas MS, et al. Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy. Am J Gastroenterol 2001;96: Stewart CA, Smith GE. Minimal hepatic encephalopathy. Nat Clin Pract Gastroenterol Hepatol 2007;4: Ferenci P, Lockwood A, Mullen K, et al. Hepatic encephalopathy definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, Hepatology 2002;35: Das A, Dhiman RK, Saraswat VA, et al. Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis. J Gastroenterol Hepatol 2001;16: Mullen K, Ferenci P, Bass NM, et al. An algorithm for the management of hepatic encephalopathy. Semin Liver Dis 2007;27: Wein C, Koch H, Popp B, et al. Minimal hepatic encephalopathy impairs fitness to drive. Hepatology 2004;39: Schomerus H, Hamster W, Blunck H, et al. Latent portasystemic encephalopathy. I. Nature of cerebral functional defects and their effect on fitness to drive. Dig Dis Sci 1981;26: Bajaj JS, Hafeezullah M, Hoffmann RG, et al. Minimal hepatic encephalopathy: a vehicle for accidents and traffic violations. Am J Gastroenterol 2007;102: Barkley RA, Murphy KR, Dupaul GI, et al. Driving in young adults with attention deficit hyperactivity disorder: knowledge, performance, adverse outcomes, and the role of executive functioning. J Int Neuropsychol Soc 2002;8: Bajaj JS, Hafeezullah M, Hoffmann RG, et al. Navigation skill impairment: Another dimension of the driving difficulties in minimal hepatic encephalopathy. Hepatology 2008;47: Wechsler D. Wechsler Adult Intelligence Scale-III. Psychological Corp.; Bajaj JS, Saeian K, Verber MD, et al. Inhibitory control test is a simple method to diagnose minimal hepatic encephalopathy and predict development of overt hepatic encephalopathy. Am J Gastroenterol 2007;102: Gerber T, Schomerus H. Hepatic encephalopathy in liver cirrhosis: pathogenesis, diagnosis and management. Drugs 2000;60: Bajaj JS, Etemadian A, Hafeezullah M, et al. Testing for minimal hepatic encephalopathy in the United States: an AASLD survey. Hepatology 2007;45: Vergara-Gomez M, Flavia-Olivella M, Gil-Prades M, et al. [Diagnosis and treatment of hepatic encephalopathy in Spain: results of a survey of hepatologists]. Gastroenterol Hepatol 2006;29: Dangleben DA, Jazaeri O, Wasser T, et al. Impact of cirrhosis on outcomes in trauma. J Am Coll Surg 2006;203: Demetriades D, Constantinou C, Salim A, et al. Liver cirrhosis in patients undergoing laparotomy for trauma: effect on outcomes. J Am Coll Surg 2004;199: Bajaj JS, Ananthakrishnan A, McGinley A, et al. Deleterious effect of cirrhosis on outcomes after motor vehicle crashes using the Nationwide Inpatient Sample. Am J Gastroenterol 2007 (in press). 22. Murray KF, Carithers RL Jr. AASLD practice guidelines: evaluation of the patient for liver transplantation. Hepatology 2005;41: Barkley RA, Cox D. A review of driving risks and impairments associated with attention-deficit/hyperactivity disorder and the effects of stimulant medication on driving performance. J Safety Res 2007;38: Fischer M, Barkley RA, Smallish L, et al. Hyperactive children as young adults: driving abilities, safe driving behavior, and adverse driving outcomes. Accid Anal Prev 2007;39: Prochaska JORC, Evers K. The transtheoretical model and stages of change. Jossey-Bass, Inc., Ries ML, Jabbar BM, Schmitz TW, et al. Anosognosia in mild cognitive impairment: relationship to activation of cortical midline structures involved in self-appraisal. J Int Neuropsychol Soc 2007;13: Fischer S, Trexler LE, Gauggel S. Awareness of activity limitations and prediction of performance in patients with brain injuries and orthopedic disorders. J Int Neuropsychol Soc 2004;10: Amador XF, Flaum M, Andreasen NC, et al. Awareness of illness in schizophrenia and schizoaffective and mood disorders. Arch Gen Psychiatry 1994;51: Starkstein SE, Jorge R, Mizrahi R, et al. Insight and danger in Alzheimer s disease. Eur J Neurol 2007;14: Hunt L, Morris JC, Edwards D, et al. Driving performance in persons with mild senile dementia of the Alzheimer type. J Am Geriatr Soc 1993;41: Weissenborn K. Hepatic encephalopathy. Philadelphia: Saunders, Address requests for reprints to: Jasmohan S. Bajaj, MD, MS, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 9200 W Wisconsin Avenue, Milwaukee, Wisconsin jasmohan. bajaj@va.gov. The authors disclose no financial conflicts of interest.