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Pharmacotherapy of posttraumatic cognitive impairments.

Pharmacotherapy may contribute to the rehabilitation of persons with posttraumatic cognitive impairments. This article reviews first the neurobiological consequences of traumatic brain injury with a particular emphasis on acute and long-term posttraumatic neurochemical disturbances. Studies of pharmacotherapies for posttraumatic cognitive impairments are reviewed next, and are organized according to medication class and the neurotransmitter system they affect most. Based on the evidence provided by that review, augmentation of posttraumatic cerebral catecholaminergic and cholinergic function are suggested as potentially useful neurochemical targets for pharmacologic intervention in this population. More specifically, it is suggested that persons with posttraumatic impairments in arousal, speed of processing, and possibly attention may benefit most from treatment with an agent that augments cerebral catecholaminergic function, and that persons whose predominant posttraumatic impairment is in the domain of memory may benefit most from treatment with cholinesterase inhibitors. Practical considerations regarding the use of pharmacotherapies for posttraumatic cognitive impairments are offered, and the need for additional research in this area is highlighted.

Adrenergic Agents↗

Cognition-enhancing effects of donepezil in traumatic brain injury.

The purpose of this study was to investigate the effects of donepezil, a cholinergic agent, on chronic cognitive impairment due to traumatic brain injury (TBI). Chronic patients underwent two standardized neuropsychological evaluations--one before and the other 3 months following treatment with donepezil. Together with global inventories that appraised behaviour, fatigue, anxiety and depression, these evaluations also assessed executive functioning, memory and attention. Of the 10 patients who followed the therapy, 8 reported subjective improvement in at least one cognitive domain following therapy and most of them reported better functioning in everyday activities. This effect was supported by a slight global improvement when considering the global score of the different affectivo-behavioural scales. At the neuropsychological level, although we could observe a slight improvement in the majority of the considered tests, significant positive changes were mainly found in tests assessing speed of processing, learning and divided attention. These findings suggest that donepezil may lead to better general functioning and improve attentional skills in patients with chronic TBI.

Adult↗

Cognitive outcome in adult women affected by congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

BACKGROUND: Some research suggests that girls with congenital adrenal hyperplasia (CAH), who are exposed to higher than normal levels of prenatal androgens, perform better on spatial tasks, worse on verbal tasks and have a greater incidence of left-handedness than unaffected controls, all of which suggests the development of a more male-typical cognitive pattern. However, research in all three areas has produced inconsistent findings. OBJECTIVES: To determine if prenatal androgen exposure has an organizing effect on female cognitive development and to what extent. METHODS: 24 women, 21-71 years, with either the salt-losing (SL) or simple virilizing (SV) forms of CAH due to 21-hydroxylase deficiency, and 18 controls, 21-73 years, who were unaffected female relatives or women with polycystic ovary syndrome, were assessed with IQ, handedness, executive function, verbal learning and memory, non-verbal learning and memory, perceptual speed, visuospatial processing and visuomotor ability measures. The battery included tests known to elicit sex differences and control measures. RESULTS: The findings did not support the hypothesis that women with CAH develop a more male-typical cognitive pattern. CONCLUSION: This study differs from others in the older age of its participants, grouping by SL/SV diagnosis and assessment of medical treatment and compliance as determined through hormone assays. Our findings provide additional support for the conclusion that, in adult women with CAH, previous prenatal androgen exposure does not enhance spatial abilities, impair verbal abilities nor alter hand preferences in a long-lasting way.

Adrenal Hyperplasia, Congenital↗

The impact of raising blood glucose on reaction times.

Although previous studies have demonstrated enhanced mood and memory in humans following the consumption of glucose drinks, the effect of increasing blood glucose levels on other tasks has not received the same attention. In the present study, inspection time was unaffected by glucose drinks and blood glucose levels. However, increasing blood glucose levels resulted in faster decision times when reaction time was measured. It is concluded that speed of processing is faster when the availability of glucose to the brain is increased. The possibility that the glucose-induced improvements in reaction time reflect an increased synthesis of acetylcholine is discussed.

Adolescent↗

Negative symptoms in temporal lobe epilepsy.

OBJECTIVE: This study examined the frequency of negative and positive symptoms in nonpsychotic patients with temporal lobe epilepsy and the relationship of negative and positive symptoms to cognition, quantitative magnetic resonance imaging (MRI) volumetrics, and depression. METHOD: Eighty-four patients with temporal lobe epilepsy and 74 healthy comparison subjects were evaluated for negative and positive symptoms and underwent comprehensive neuropsychological evaluation, quantitative MRI volumetrics, and assessment of mood state and depression. RESULTS: Negative symptoms were significantly more prevalent in the patients with temporal lobe epilepsy (31%) than in the comparison subjects (8%). There was no difference between groups in the rate of positive symptoms. Although the epilepsy patients as a group exhibited generalized cognitive impairment relative to the comparison subjects, the epilepsy patients with negative symptoms performed significantly worse than patients without negative symptoms and comparison subjects across measures of nonverbal intelligence, visuoperception, speeded visuomotor processing, and memory. The epilepsy patients with negative symptoms exhibited significantly greater diffuse atrophy than the healthy comparison subjects and higher CSF volumes than the epilepsy patients without negative symptoms. The epilepsy patients with and without negative symptoms had statistically equivalent Beck Depression Inventory scores and lifetime history of mood disorders, including major depression. CONCLUSIONS: Negative but not positive symptoms were more prevalent in temporal lobe epilepsy patients than in healthy comparison subjects. Negative symptoms were independent of current and past depression and were associated with neuropsychological deficits exceeding the general cognitive morbidity associated with temporal lobe epilepsy and with quantitative MRI indices suggesting greater cerebral atrophy.

Adolescent↗

Mathematical outcomes of attention-deficit hyperactivity disorder.

We assessed the academic performance and behavior of 121 nondisabled elementary boys and 107 boys with attention-deficit hyperactivity disorder (ADHD), ages 7.4 through 14.5 years. Students completed computer-generated tasks of reading, computation, and math problem solving, and we recorded two performance measures (accuracy and speed) and three behavioral measures (vocalizations, head movements, and bottom movements). Our purpose was to determine the effects of ADHD on conceptual and computational math. For greater precision than has been available in past math research, we held reading and problem structure constant, while recording speed of processing, number recognition, and motor response. Our analysis yielded significantly lower problem-solving scores in specific math concepts and slower computational performance for the boys with ADHD. These findings demonstrated the educational implications of attention deficit disorders for mathematical skill and the need for interventions that are geared more specifically to these deficits, and that also provide accommodations for reading complexity and length, visual-motor skill, feedback, and self-pacing.

Attention Deficit Disorder with Hyperactivity↗

Bimodal reading: benefits of a talking computer for average and less skilled readers.

Studies have shown that when information is presented through visual and auditory channels simultaneously (i.e., bimodal presentation), speed of processing and memory recall are enhanced. The present study demonstrated the efficacy of a bimodal approach to fostering reading comprehension. Eighteen average readers (9 girls and 9 boys) and 18 less skilled readers (8 girls and 10 boys) in Grades 8 and 9 participated in the study. Students were presented with social studies and science passages via a computer. Passages were presented in three conditions: visually (on screen), auditorily (read by digitized voice), and bimodally (on screen, highlighted, while being voiced). Following each passage, students answered 10 oral-response, short-answer comprehension questions. Results indicated that less skilled readers comprehended more with bimodal versus unimodal presentations. Overall, their performance in the bimodal condition was commensurate with average readers' comprehension in the visual condition. For less skilled readers, an increase in word recognition from pre- to posttesting on word lists was found across conditions. In addition, results of a brief consumer satisfaction survey suggested that low-skilled readers felt most successful in terms of their comprehension when passages were presented bimodally. Several clinical issues involved in presenting information bimodally using computers are discussed.

Adolescent↗

Hysterosalpingo contrast sonography as a screening test for tubal patency in infertile women.

The most informative method for assessing tubal patency in subfertile women is laparoscopy-and-dye. This investigation, however, puts a large burden on services and a screening test is needed that identifies a high likelihood of occlusion. In our infertility programme we introduced hysterosalpingo contrast sonography for this purpose, operated entirely by ultrasonographers. A series of audits indicated that this innovation speeded the process of investigation by several weeks and reduced the number of laparoscopy-and-dye procedures by 75%. The negative predictive value was 89% and the positive predictive value was 44%. The main limitation of the method was the long period required for training, in those without extensive experience of vaginal ultrasonography.

Contrast Media↗

Perception of quantitative information for treatment decisions.

The study was designed to determine which formats for displaying quantities, such as probabilities of treatment risks and benefits, are perceived most accurately and easily by patients. Accuracy and speed of processing were compared for six different presentation formats: pie charts, vertical bars, horizontal bars, numbers, systematic ovals, and random ovals. Quantities were used in two tasks: a choice task that required larger/smaller judgments and an estimate task that required more precise evaluation. The impacts of blue-yellow color and of a treatment-decision context on performance in the two tasks were also investigated. The study included four experiments. Taken together the results suggest that the formats best for making a choice differ from those best for estimating the size of an amount. For making a choice, vertical bars, horizontal bars, numbers, and systematic ovals were equally well perceived; pie charts and random ovals caused slower and less accurate performances. For estimating, numbers led to the most accurate estimates, followed by systematic ovals. The other four formats led to the least accurate estimates. Color and context did not alter which formats were best.

Data Display↗

Update on childhood immunizations.

OBJECTIVE: To provide an overview of childhood immunizations with emphasis in new recommendations, as well as recent vaccine developments and special populations. DATA SOURCES: English language literature identified via a MEDLINE search. Additional references were obtained from cited references. STUDY SELECTION AND DATA EXTRACTION: Original articles, reviews, and official publications were used to obtain the most accurate data on safety and efficacy of available pediatric vaccines, as well as current recommendations for their use. DATA SYNTHESIS: Immunizations have been an area of vigorous research for several years. New vaccines have been developed by improving older products to maximize immunogenicity and minimize adverse effects. Some of these novel vaccines, like the Haemophilus influenzae type b conjugate vaccines (HibCV), have already contributed significantly to the prevention of diseases in childhood. New recommendations have been issued to help speed this process. Adverse effects of routine immunizations are generally mild and transient. CONCLUSIONS: The development of new effective and safe vaccines for children is an important step in the global eradication of contagious diseases. A new generation of combination vaccines has started with the combination of the diphtheria-tetanus-pertussis vaccine and HibCV. Some other combined products are yet to come that would eventually make immunization schedules more cost-effective and improve compliance rates. Our colleagues in the community and in the ambulatory care setting must actively participate in the implementation of vaccination programs and provide education to parents regarding all aspects of the immunization process.

Bacterial Capsules↗

Cytogenetic and Molecular Evaluation in Myelodysplastic Syndrome and in Acute and Chronic Leukemia.

BACKGROUND: The majority of the presently known nonrandom chromosome changes in hematologic malignancy were described during the 1970s and 1980s. The last 10 years have been devoted to the location of oncogenes and tumor suppressor genes altered as a consequence of those changes. New molecular methodology has helped speed this process, which has resulted in DNA sequencing of many of the genes involved, permitting molecular detection of abnormal clones. METHODS: This review examines the most common alteration-based subgroups of cytogenetics and molecular genetics in hematologic disorders with the exclusion of lymphoma. Prognosis has been updated to reflect improving treatment protocols. RESULTS: The versatility of cytogenetics for delineating genetic changes is difficult to match by molecular testing. Once a clonal anomaly is identified, molecular methodology can detect residual disease with far greater sensitivity than cytogenetics, but relies on translocation junction targets that exclude clones characterized by deletion or trisomy. CONCLUSIONS: Cytogenetic and molecular testing offers independent diagnostic and prognostic evaluation for most patients with hematologic malignancy.

Journal Article↗

The association between cognitive impairment and physical disability in multiple sclerosis.

BACKGROUND: The association between cognitive impairment and physical disability was examined in a larger, more representative sample of patients with multiple sclerosis (MS) than in previous studies. METHOD: Two hundred and fifty-three patients attending an MS clinic were assessed with respect to physical disability using the Expanded Disability Status Scale and cognitive impairment using a battery of neuropsychological tests. RESULTS: Physical disability correlated with duration of disease; cognitive impairment did not. Virtually all measures derived from the cognitive battery were significantly correlated with physical disability. Three measures of speeded information processing and one involving delayed recall of verbal material were unique predictors of disability status. The relationship between cognitive impairment and physical disability was equivalent for patients with shorter (< 3 years) versus longer (> 10 years) disease duration. Cognitive impairment correlated with the rate of disability progression as reflected by the progression index. CONCLUSION: Cognitive impairment is more closely associated with physical disability than most previous studies indicate. This relationship appears to be stable throughout the duration of MS, although this conclusion is qualified by the cross-sectional design of the study. Further attention should be paid to cognitive impairment as a possible predictor of the rate of patients' physical decline.

Adult↗

Biphasic patterns of memory deficits following moderate-dose partial-brain irradiation: neuropsychologic outcome and proposed mechanisms.

PURPOSE: To identify the longitudinal neurobehavioral characteristics of the early-delayed and late-delayed effects of partial-brain radiotherapy for patients with supratentorial brain tumors with favorable histology. This study improves on previous attempts to identify radiation effects, because of the inclusion of baseline measures and the use of subjects as their own controls. PATIENTS AND METHODS: Ten neuropsychologic domains were measured in 12 patients at baseline (post-surgery and immediately before initiation of radiotherapy), and followed trimonthly for 1 year. Four to six patients were examined at 2 and 3 years postbaseline. RESULTS: Patients were impaired at baseline compared with controls only in visual memory and sentence recall, but demonstrated significant improvement in visual memory by 2 years postbaseline. Speed of processing information also showed a slope of improvement over 2 years. Retrieval from verbal long-term memory was impaired at 1.5 months postcompletion of radiotherapy, but recovered to baseline levels by 1 year. At 2 years postbaseline, long-term memory retrieval demonstrated a decline, but remained unchanged at 3 years. CONCLUSION: Long-term memory appears to be sensitive to the effects of radiotherapy. We confirmed our previous findings of a decrement with rebound during the early-delayed period, and propose that these findings are consistent with demyelination/remyelination. Decrement was observed again at 2 years postbaseline, which suggests that memory retrieval may be the earliest marker of late-delayed effects. These neurocognitive patterns are consistent with leukoencephalopathy. Confirmation of these observations will be possible if neuropsychologic testing with the same sensitivity can be incorporated into national collaborative trials.

Adult↗

Neuropsychological deficit profiles in systemic lupus erythematosus.

Although neuropsychological deficits have been reported in several cognitive domains in patients with systemic lupus erythematosus (SLE), there is considerable variability in the literature about which neuropsychological domains are most affected. Similar to studies that demonstrated that specific profiles of neuropsychological deficits exist for those with traumatic brain injury (TBI; Johnstone, Hexum, & Ashkanazi, 1995), this study examined whether a specific pattern of deficits is present in SLE. By comparing reading scores (as estimates of premorbid ability) to tests of concurrent cognitive abilities (i.e., memory, attention, etc.), it was determined that SLE presents a profile distinct from TBI, with the most significant impairments noted in expressive language (Zdiff = -1.39), attention (Zdiff = -0.41), and speed of processing (Zdiff = -0.40). In contrast to TBI, no impairment was noted in intelligence, memory, or cognitive flexibility. Results suggest that memory problems reported by individuals with SLE may be related to inattention. Clinical implications are discussed.

Adult↗

Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine.

OBJECTIVE: To examine the contribution of hepatitis C virus (HCV) infection to neurocognitive dysfunction in individuals with comorbid HIV infection or methamphetamine (METH) dependence. METHODS: Neurocognitive functioning was examined in 430 study participants who were either normal controls or had HCV infection, HIV infection, history of METH dependence, or combinations of these factors as risks for cognitive deficits. RESULTS: Rates of global and domain-specific neuropsychological (NP) impairment increased with the number of risk factors. HCV serostatus was a significant predictor of NP performance both globally and in the areas of learning, abstraction, and motor skills, with trends in speeded information processing and delayed recall. HCV serostatus did not predict scores in attention/working memory or verbal fluency. CONCLUSION: Hepatitis C virus infection contributes to the neuropsychological deficits observed among HIV-infected and stimulant-dependent populations.

AIDS Dementia Complex↗

Microsurgical lumbar discectomy: preliminary report of 83 consecutive cases.

The application of microsurgical technique to lumbar discectomy may be of dual value: minimal disruption of the integrity of normal anatomy and meticulous hemostasis may help to speed the process of convalescence, and the retention of epidural fat around the nerve root may help to prevent adhesions, a common cause of the late, "failed disc" syndrome. The authors report their experience with 83 consecutive microdiscectomies for lumbar disc protrusions. The results must be considered as tentative because the follow-up period has been short and the authors found it difficult to quantify the quality of health during the convalescent phase, although this seemed to be excellent. Their short term results are similar to those of the larger series reported by Williams, whose experience with microsurgical lumbar discectomies began 6 years ago. No other series have been reported. The authors describe their technique and compare it to that of Williams.

Adult↗