Robin C. Hilsabeck

Cognitive functioning and psychiatric symptomatology in patients with chronic hepatitis C

Hepatitis C virus (HCV) infection is a major public-health-care problem, with over 170 million infected worldwide. Patients with chronic HCV infection often complain of various cognitive problems as well as symptoms of depression, anxiety, and fatigue. Relatively little is known, however, about the specific cognitive deficits that are common among HCV patients, and the influence of psychiatric symptomatology on cognitive functioning. In the current study of 21 chronically infected HCV patients, we assessed subjective cognitive dysfunction, depression, anxiety, and fatigue and compared these symptom areas to cognitive tests assessing visuoconstruction, learning, memory, visual attention, psychomotor speed, and mental flexibility. Results revealed that cognitive impairment ranged from 9% of patients on a visuoconstruction task to 38% of patients on a measure of complex attention, visual scanning and tracking, and psychomotor speed, and greater HCV disease severity as indicated by liver fibrosis was associated with greater cognitive dysfunction. Objective cognitive impairment was not related to subjective cognitive complaints or psychiatric symptomatology. These findings suggest that a significant portion of patients with chronic HCV experience cognitive difficulties that may interfere with activities of daily living and quality of life. Future research using cognitive measures with HCV-infected patients may assist researchers in identifying if there is a direct effect of HCV infection on the brain and which patients may be more likely to progress to cirrhosis and hepatic encephalopathy.

Neuropsychological assessment of hepatic encephalopathy: ISHEN practice guidelines

Low‐grade or minimal hepatic encephalopathy (MHE) is characterised by relatively mild neurocognitive impairments, and occurs in a substantial percentage of patients with liver disease. The presence of MHE is associated with a significant compromise of quality of life, is predictive of the onset of overt hepatic encephalopathy and is associated with a poorer prognosis for outcome. Early identification and treatment of MHE can improve quality of life and may prevent the onset of overt encephalopathy, but to date, there has been little agreement regarding the optimum method for detecting MHE. The International Society on Hepatic Encephalopathy and Nitrogen Metabolism convened a group of experts for the purpose of reviewing available data and making recommendations for a standardised approach for neuropsychological assessment of patients with liver disease who are at risk of MHE. Specific recommendations are presented, along with a proposed methodology for further refining these assessment procedures through prospective research.

Neuropsychological Aspects of Coinfection with HIV and Hepatitis C Virus

Infection with hepatitis C virus (HCV) is commonly seen in persons with human immunodeficiency virus (HIV) infection, because the viruses share risk factors for transmission; coinfection is a leading cause of morbidity and mortality among HIV-infected persons. Neuropsychological consequences of HIV infection are well established, and studies of HCV-infected persons have revealed neuropsychiatric dysfunction in this population as well. Investigators now are focusing on neuropsychological sequelae of coinfection with HIV and HCV, and preliminary results suggest that coinfection has a possible deleterious effect on global cognitive functioning consistent with frontal-subcortical dysfunction. Data on neuropsychiatric symptoms in coinfected persons are inconclusive at this time and are complicated by important differences in study populations (e.g., injection drug use and disease severity). This review summarizes what is known about neuropsychological aspects of monoinfection with HIV and HCV, as well as coinfection, discusses implications of these findings, and suggests future directions for this research area.

Performance of the Hepatic Encephalopathy Scoring Algorithm in a Clinical Trial of Patients With Cirrhosis and Severe Hepatic Encephalopathy

OBJECTIVES:The grading of hepatic encephalopathy (HE) is based on a combination of indicators that reflect the state of consciousness, intellectual function, changes in behavior, and neuromuscular alterations seen in patients with liver failure.METHODS:We modified the traditional West Haven criteria (WHC) to provide an objective assessment of the cognitive parameters to complement the subjective clinical ratings for the performance of extracorporeal albumin dialysis (ECAD) using a molecular adsorption recirculating system in patients with cirrhosis and severe (grade III/IV) encephalopathy. The HE Scoring Algorithm (HESA) combined clinical indicators with those derived from simple neuropsychological tests, the latter more often used in milder grades of HE (I/II). The performance of each indicator was compared across grades and sites.RESULTS:Results of HESA were also compared with the Glasgow Coma Scale. A total of 597 evaluations were performed in patients randomized to ECAD plus standard medical therapy or the latter only. Most parameters exhibited significant separation between grades; the most effective indicators were lack of verbal, eye, and motor response (grade IV), somnolence and disorientation to place (grade III), and lethargy and disorientation to time (grade II). Two clinical and four neuropsychological indicators were useful to classify patients as grade I. The Glasgow Coma Scale differed among the four stages of the WHC, but the differences between grades I and II were small and not clinically useful.CONCLUSION:HESA extends the traditional WHC for grading HE. In the absence of a “gold” standard, the most useful indicators noted in this trial should be further validated.

Neuropsychological test performance in patients co-infected with hepatitis C virus and HIV.

Objective:To determine the effect of co-infection on neuropsychological performance in relatively healthy hepatitis C virus (HCV)-alone patients when compared with HCV/HIV-co-infected patients. Design:To test whether the burden of co-infection with HCV and HIV on the central nervous system results in increased cognitive deficits, we tested 47 HCV-alone and 29 HCV/HIV-co-infected patients on a neuropsychological screening battery of tests of attention, concentration and psychomotor speed. Methods:The neuropsychological test performance of HCV-alone and HCV/HIV-co-infected patients was compared with normative samples. The test performance between HCV-alone and HCV/HIV-co-infected patients was also assessed. Patients with chronic liver disease were divided on the basis of disease severity as determined by fibrosis stage, according to the METAVIR system. Neuropsychological test performance was correlated with fibrosis stage. Results:As previously reported, HCV patients independent of co-infection status demonstrated deficits on neuropsychological measures of attention, concentration and psychomotor speed. No significant differences were found between patients with HCV-alone and HCV/HIV-co-infected patients on the neuropsychological measures. There was a relationship between neuropsychological test performance and fibrosis stage. Conclusion:Relatively healthy patients with HCV (either alone or when co-infected with HIV) may have deficits in the domains of attention, concentration and psychomotor speed. In this study no significant differences were found between patients with HCV alone and HCV/HIV-co-infected patients on neuropsychological measures, but as previously demonstrated, greater fibrosis was associated with poorer performance.

Effect of interferon-α on cognitive functioning in patients with chronic hepatitis C

Treatment with interferon-alpha (IFN-alpha) has been shown to adversely affect cognitive functioning in patients with a variety of medical disorders, but information about the effects of IFN-alpha on cognitive functioning in patients with chronic hepatitis C (CHC) is limited. The purpose of this study was to examine the effects of IFN-alpha on neuropsychological test performance in CHC patients. Participants were 30 patients with CHC, 11 who underwent IFN-alpha therapy and 19 who did not. All participants were tested at baseline (i.e., pretreatment) and approximately 6 months later with the Symbol Digit Modalities Test and Trail Making Test. Results revealed that the treatment group performed significantly worse than untreated CHC patients on Part B of the Trail Making Test after approximately 6 months of treatment. No significant group differences were found on Part A of the Trail Making Test or Symbol Digit Modalities Test. Findings suggest that CHC patients undergoing treatment with IFN-alpha may experience reduced abilities to benefit from practice but suffer no decrements in performance after 6 months of treatment. Additional research is needed to replicate these findings and to explore risk factors for susceptibility to IFN-alpha-induced effects.

Assessment of cognition in early dementia.

Better tools for assessing cognitive impairment in the early stages of Alzheimers disease (AD) are required to enable diagnosis of the disease before substantial neurodegeneration has taken place and to allow for detection of subtle changes in the early stages of progression of the disease. The National Institute on Aging and the Alzheimers Association convened a meeting to discuss state‐of‐the art methods for cognitive assessment, including computerized batteries, as well as new approaches in the pipeline. Speakers described research using novel tests of object recognition, spatial navigation, attentional control, semantic memory, semantic interference, prospective memory, false memory, and executive function as among the tools that could provide earlier identification of individuals with AD. In addition to early detection, there is a need for assessments that reflect real‐world situations so as to better assess functional disability. It is especially important to develop assessment tools that are useful in ethnically, culturally, and linguistically diverse populations as well as in individuals with neurodegenerative disease other than AD.

No Effect of PTSD and Other Psychiatric Disorders on Cognitive Functioning in Veterans with Mild TBI

There has been speculation that post-traumatic stress disorder (PTSD) superimposed on mild traumatic brain injury (mTBI) may have synergistic, negative effects on cognitive functioning. The purpose of this study was to investigate differences in processing speed, executive functioning, and memory of 82 veterans with mTBI and PTSD, mTBI, and another psychiatric condition, or mTBI alone. It was hypothesized that there would be no group differences in cognitive performances. Participants completed the Trail Making Test, Stroop, Rey Complex Figure, and California Verbal Learning Test-2. There were no significant group differences on any cognitive measure. Findings suggest that PTSD and other psychiatric disorders do not necessarily have a negative exacerbating effect on processing speed, executive functioning, or memory in veterans with mTBI.

Utility of the Trail Making Test in the Assessment of Malingering in a Sample of Mild Traumatic Brain Injury Litigants

The Trail Making Test (TMT) is one of the most commonly administered tests in neuropsychological assessments. It has been shown to be a valid indicator of brain damage due to traumatic brain injury (TBI), as well as a number of other neuropathological conditions. TMT error and ratio scores have been suggested as possible markers of malingering. The present study examined the utility of various TMT scores as malingering measures in 94 TBI litigants. Litigants were divided into those suspected of (n =27) and those not suspected of malingering (n =67) based on scores obtained on the Test of Memory Malingering and/or the Rey 15-Item Test. TMT errors did not discriminate between suspected and nonsuspected malingerers; however, the overall level of performance on the TMT was suppressed in suspected malingerers. The TMT ratio score was significantly lower in litigants suspected of malingering, although the clinical utility of this ratio is minimal. Results of the present study suggest using caution when interpreting TMT scores as markers of malingering in TBI litigants.

Neuropsychiatric Complications of Interferons: Classification, Neurochemical Bases, and Management

BACKGROUND Recombinant interferons are widely used for a number of serious illnesses. However, their use is sometimes associated with severe and disabling neuropsychiatric side effects. METHODS A MEDLINE search identified pertinent laboratory investigations, case reports, clinical studies and letters published between 1983 and 2004 in the English language journals. The studies in which interferons were used in combination with other cytokines were excluded. RESULTS The interferon-associated neuropsychiatric side effects are divided into mood-related symptoms (depression/mania), cognitive impairment (including delirium), psychosis and isolated psychiatric symptoms. Putative neurotransmitters (serotonin and dopamine), hormones (cortisol) and cyokines (interleukin-2 and 6) have been implicated in the pathophysiology of these side effects. Management of neuropsychiatric side effects of interferons ranges from supportive measures, dose reduction, cessation of therapy and the use of appropriate psychotropic agents. CONCLUSIONS Interferon-treated patients should be monitored for mental status changes. There are no controlled studies on pharmacological management of interferon-induced neuropsychiatric side effects. The use of interferons in patients with stable psychiatric disorders is not contraindicated. However, such patients should be closely monitored during the course of treatment with interferons.