Alan B. Frol

Interrater Reliability of Clinical Ratings and Neurocognitive Diagnoses in HIV

We examined the interrater reliability (IRR) of clinical ratings of neuropsychological (NP) impairment and neurocognitive diagnoses in HIV. Thirty participants with advanced HIV-infection who were enrolled in a multicenter HIV brain banking research project underwent comprehensive NP and neuromedical evaluations. Using a standardized system of guidelines, neuropsychologists from six participating sites independently assigned clinical ratings of NP impairment, as well as multilevel diagnoses reflecting the inferred etiology of the impairments and their effects on everyday functioning. Findings indicated excellent IRR in rating the presence and severity of NP impairment, but overall modest IRR for neurocognitive diagnoses. Not surprisingly, most diagnostic disagreements concerned the etiology of impairments in persons with medical and neuropsychiatric risk factors in addition to HIV.

Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid therapy

BACKGROUND Hippocampal volume reduction, declarative memory deficits, and cortisol elevations are reported in persons with major depressive disorder; however, data linking cortisol elevations with hippocampal atrophy are lacking. Prescription corticosteroid-treated patients offer an opportunity to examine corticosteroid effects on hippocampal volume and biochemistry and memory in humans. METHODS Seventeen patients on long-term prescription corticosteroid therapy and 15 controls of similar age, gender, ethnicity, education, height, and medical history were assessed with magnetic resonance imaging and proton magnetic resonance spectroscopy, the Rey Auditory Verbal Learning Test, Stroop Color Word Test and other neurocognitive measures, the Hamilton Rating Scale for Depression, Young Mania Rating Scale, and Brief Psychiatric Rating Scale. RESULTS Compared with controls, corticosteroid-treated patients had smaller hippocampal volumes and lower N-acetyl aspartate ratios, lower scores on the Rey Auditory Verbal Learning Test and Stroop Color Word Test, and higher Hamilton Rating Scale for Depression and Brief Psychiatric Rating Scale scores. CONCLUSIONS Patients receiving chronic corticosteroid therapy have smaller hippocampal volumes, lower N-acetyl aspartate ratios, and declarative memory deficits compared with controls. These findings support the idea that corticosteroid exposure appears to be associated with changes in hippocampal volume and functioning in humans.

Impact of Age on Long-Term Recovery From Traumatic Brain Injury

OBJECTIVE To determine whether older persons are at increased risk for progressive functional decline after traumatic brain injury (TBI). DESIGN Longitudinal cohort study. SETTING Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers. PARTICIPANTS Subjects enrolled in the TBIMS national dataset. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Disability Rating Scale (DRS), FIM instrument cognitive items, and the Glasgow Outcome Scale-Extended. RESULTS Participants were separated into 3 age tertiles: youngest (16-26y), intermediate (27-39y), and oldest (> or =40y). DRS scores were comparable across age groups at admission to a rehabilitation center. The oldest group was slightly more disabled at discharge from rehabilitation despite having less severe acute injury severity than the younger groups. Although DRS scores for the 2 younger groups improved significantly from year 1 to year 5, the greatest magnitude of improvement in disability was seen among the youngest group. In addition, after dividing patients into groups according to whether their DRS scores improved (13%), declined (10%), or remained stable (77%) over time, the likelihood of decline was found to be greater for the 2 older groups than for the youngest group. A multiple regression model showed that age has a significant negative influence on DRS score 5 years post-TBI after accounting for the effects of covariates. CONCLUSIONS This study supported our primary hypothesis that older patients show greater decline over the first 5 years after TBI than younger patients. In addition, the greatest amount of improvement in disability was observed among the youngest group of survivors. These results suggest that TBI survivors, especially older patients, may be candidates for neuroprotective therapies after TBI.

Effect of two prednisone exposures on mood and declarative memory

Corticosteroids are essential for life and an integral part of the stress response. However, in excess, corticosteroids can be associated with a variety of effects on the brain including hippocampal atrophy and even neuronal death, mood changes, and declarative memory impairment. The magnitude of mood change in patients receiving prednisone is reportedly associated with previous lifetime corticosteroid exposure, consistent with a sensitization or kindling process whereby greater effects are observed with repeated exposure. To our knowledge, the effect of multiple corticosteroid exposures on mood and memory has not been previously examined prospectively in animals or humans. In this study, 30 human volunteers, with no history of systemic prescription corticosteroid therapy, were given (in random order using a crossover design) two 3-day exposures of prednisone (60 mg/day) and one of identical placebo, with 11-day washouts between each medication exposure. Before and after each 3-day prednisone/placebo exposure, declarative memory was assessed using different versions of the Rey Auditory Verbal Learning Test (RAVLT) to minimize practice or learning effects, while mood was assessed with the 21-item Hamilton Rating Scale for Depression, Young Mania Rating Scale and Internal State Scale. No significant mood changes were found. However, a significant decrease in aspects of RAVLT performance was observed after the first prednisone exposure consistent with a decline in declarative memory performance. The decline in RAVLT performance was significantly smaller after the second prednisone exposure as compared to the initial prednisone exposure. Thus, a second prednisone exposure was associated with an attenuated prednisone-effect on declarative memory. These data suggest tolerance or habituation, rather than sensitization, to prednisone effects on declarative memory during a second exposure. Implications and possible explanations for the findings are discussed.

Deep Venous Thrombosis Management Following Traumatic Brain Injury: A Practice Survey of the Traumatic Brain Injury Model Systems

ObjectiveTo determine national patterns of screening, prophylaxis, and treatment of deep venous thrombosis (DVT) following traumatic brain injury (TBI) within the Traumatic Brain Injury Model Systems (TBIMS). Designe-mail survey instrument. SettingMulticenter Regional TBIMS. ResultsFifteen of the 16 rehabilitation centers within the TBIMS responded to the survey (94% response rate). Approximately half of these centers routinely screen to detect subclinical DVTs (56% venous duplex ultrasonography, 12% plasma D-dimer) on admission to inpatient rehabilitation. Fifty-six percent of respondents use anticoagulation prophylactically, while 69% use mechanical means for DVT prophylaxis. Eighty fatal pulmonary emboli were reported for TBI patients in 189 practice-years, corresponding to 0.42 fatalities per year of practice. ConclusionsNo consensus exists regarding the optimal methods for screening, prevention, or treatment of DVT in TBI patients in the acute rehabilitation setting of the TBIMS. The number of fatal pulmonary emboli reported among these centers emphasizes the need to develop evidence-based clinical practice guidelines for the prevention and treatment of venous thromboembolism in this patient population.

Open-label nefazodone in patients with a major depressive episode and alcohol dependence.

PURPOSE Major depressive disorder (MDD) and alcohol dependence (AD) frequently occur together. However, MDD clinical trials generally exclude patients with alcohol-related disorders. GENERAL METHODS A 12-week, open-label trial of nefazodone in a group of people (n=13) with both a current major depressive episode and current AD was conducted to examine the effect of this antidepressant on depressive symptoms, alcohol use, and cognition. FINDINGS Scores on the Hamilton Rating Scale for Depression (HRSD) and Hamilton Rating Scale for Anxiety (HRSA) significantly decreased from baseline to exit. In addition, significant reduction in alcohol craving, drinks/week, and days of alcohol use/week was found. Scores on the Rey Auditory Verbal Learning Test (RAVLT) did not significantly improve during the study. Changes in mood/anxiety and memory did not correlate with changes in alcohol use. CONCLUSIONS Thus, nefazodone therapy was associated with improvement in mood/anxiety and alcohol use, which seem to be independent of each other in this patient sample. However, declarative memory, which was low average at baseline, did not show statistically significant improvement during the 12 weeks of the study.

Bilateral memory dysfunction in epilepsy surgery candidates detected by the intracarotid amobarbital procedure (Wada memory test)

The intracarotid amobarbital procedure (IAP) is widely used in the evaluation of candidates for resective epilepsy surgery, in part to identify patients at risk for postoperative amnesia. Yet there is no widely accepted standardized protocol, and there is a paucity of quantitative data to assess the factors associated with poor IAP performance. This report summarizes our findings on 110 patients with intractable focal epilepsy who underwent IAP testing at our center. Ipsilateral IAP scores for patients with left-sided seizure foci were significantly lower than those for patients with right-sided seizure foci. Falsely and poorly lateralizing scores were also significantly more common in subjects with left-sided seizure onsets. Twenty-four percent of subjects failed the IAP bilaterally, and patients who failed the IAP bilaterally had significantly lower scores on neuropsychologic measures. There was no difference between patients who passed and failed in the location, etiology, duration, or age of onset of epilepsy. We conclude that bilateral memory dysfunction is common in patients with intractable partial epilepsy. Whether memory dysfunction detected by IAP testing as performed at our center is predictive of functionally limiting postoperative amnesia remains to be determined.