Use of local anesthesia for inguinal hernia repair has decreased over time in the VA system.

PURPOSE: In 2003, randomized trials demonstrated potentially improved outcomes when local instead of general anesthesia is used for inguinal hernia repair. Our study aimed to evaluate how the use of local anesthesia for this procedure changed over time following the publication of the trials' level 1 evidence. METHODS: We used the 1998-2018 Veterans Affairs Surgical Quality Improvement Program database to identify adults who underwent open, unilateral inguinal hernia repair under local or general anesthesia. Our primary outcome was the percentage of cases performed under local anesthesia. We used a time-series design to examine the trend and rate of change of the use of local anesthesia. RESULTS: We included 97,437 veterans, of which 22,333 (22.9%) had hernia surgery under local anesthesia. The median age of veterans receiving local anesthesia remained stable at 64-67 years over time. The use of local anesthesia decreased steadily, from 38.2% at the beginning year to 15.1% in the final year (P < 0.0001). The publication of results from randomized trials (in 2003) did not appear to increase the overall use or change the rate of decline in the use of local anesthesia. Overall, we found that the use of local anesthesia decreased by about 1.5% per year. CONCLUSION: The utilization of local anesthesia for inguinal hernia repair in the VA has steadily declined over the last 20 + years, despite data showing equivalence or superiority to general anesthesia. Future studies should explore barriers to the use of local anesthesia for hernia repair.

Perceived Recovery and Self-Reported Functioning in Adolescents with Mild Traumatic Brain Injury: The Role of Sleep, Mood, and Physical Symptoms.

Purpose: To determine the contributions of anxiety, depressive, and concussion symptoms and sleep quality to self-perceived recovery in adolescents with concussion.Method: Adolescents aged 12-20 (n = 298) completed anxiety, depression, concussion symptoms, and sleep measures at an initial concussion clinic visit and three-month follow-up. At follow-up, they reported self-perceived recovery as percent back to normal.Results: Injury-related factors alone did not predict self-perceived recovery (R2Adj =.017, p =.074). More concurrent physical, mental health, and sleep symptoms explained 18.8% additional variance in poorer self-perceived recovery (R2Adj Change =.188, p <.05). Physical symptoms (Bstand = -.292) and anxiety (Bstand = -.260) accounted for the most variance in self-perceived recovery.Conclusion: Post-concussive symptoms, in particular anxiety and self-reported physical symptoms, seem to characterize protracted recovery. Self-perceived recovery as an outcome measure may provide a more holistic understanding of adolescents' experiences after concussion.

Detecting differential memory performance among Spanish-speaking patients with temporal lobe epilepsy.

There is relatively little research pertaining to neuropsychological assessment of Spanish-speaking individuals with intractable temporal lobe epilepsy (TLE). The current study examined verbal and visual memory performances in 38 primarily Spanish-speaking patients with TLE (Right = 15, Left = 23) of similar epilepsy duration to determine if lateralizing differences can be found using verbal and nonverbal memory tests. On a test specifically designed to assess auditory learning and memory among Spanish-speaking individuals, the Spanish Verbal Learning Test (SVLT), patients with left TLE performed significantly worse than patients with right TLE. In contrast, no significant differences in story or visual memory were seen using common memory tests translated into Spanish. Similar to what has been found in English speakers, these results show that verbal memory differences can be seen between left and right sided TLE patients who are Spanish-speaking to aid in providing lateralizing information; however, these differences may be best detected using tests developed for and standardized on Spanish-speaking patients.

Neuropsychological functioning in MRI-derived subgroups of schizophrenia.

This study examined neuropsychological functioning in two subgroups of patients with familial schizophrenia. Those who showed evidence of progressive ventricular enlargement observed across serial MRI scans (n=6) were compared with subjects whose ventricular volume remained static (n=10) over an average of 28 months. No differences were found in terms of age, education, ethnicity, level of psychotic symptomatology, DSM-IV subtype, age of onset, or duration of illness. Neurocognitively, the static ventricle group was impaired across more cognitive domains and had a larger percentage of subjects falling into the impaired range on a majority of measures, with the greatest differences on measures of attention (p<0.02) and nonverbal memory (p<0.07). These results suggest that clinically meaningful differences between these two MRI-derived subgroups of patients with schizophrenia may exist, and further underscore the heterogeneity of the illness.

Apolipoprotein E epsilon 4, other risk factors, and course of Alzheimer's disease.

BACKGROUND: The epsilon 4 allele of apolipoprotein E (apoE epsilon 4) is associated with late-onset Alzheimer's disease (AD), but its relationship to various aspects of AD has become increasingly unclear. We studied the relationship of apoE genotype in AD to educational attainment, history of heart disease or head injury, age of onset, gender, severity of illness, depression, psychotic symptoms, rate of dementia progression, and time from initial evaluation to nursing home placement. METHODS: ApoE epsilon 4 genotype was determined for 97 clinically diagnosed AD patients and 61 neuropathologically confirmed cases of AD. RESULTS: Presence of one or more epsilon 4 alleles occurred in 66% of AD cases as compared with 27% in control subjects (allele frequency was .40 for AD, .15 for control subjects). Among AD subjects there was no significant relationship between epsilon 4 alleles and educational attainment, history of heart disease, head injury, age of onset, severity of illness, depression, history of depression, rate of dementia progression, or time to nursing home placement. Marginal correlations emerged between number of epsilon 4 alleles, and delusions (p = .05) and hallucinations (p = .05). There was a trend toward increased epsilon 4 homozygosity in patients with onset between ages 65 and 70 years. CONCLUSIONS: We did not find that individuals with one or two apoE epsilon 4 alleles differed significantly in clinical course of AD from those without epsilon 4 except for a trend toward increased psychotic symptoms in the group as a whole and an increase in epsilon 4 homozygosity in patients with reported symptom onset in the late 60s.

Alzheimer's disease and its Lewy body variant: a clinical analysis of postmortem verified cases.

OBJECTIVE: The authors compared clinical findings of Alzheimer's disease and the so-called Lewy body variant of Alzheimer's disease. METHOD: Available data were analyzed on the clinical features of 58 patients with Alzheimer's disease and 24 patients with the Lewy body variant of Alzheimer's disease who underwent postmortem examination. RESULTS: The proportion of men was significantly larger in the Lewy body variant group than in the Alzheimer's disease group (66.7% versus 34.5%), and, concordantly, the Lewy body variant group was slightly taller. The prevalence of hallucinations and delusions was significantly higher in Lewy body variant subjects than the Alzheimer's disease subjects, but there were no significant differences between the two groups in educational attainment, family history of dementia, age at onset, duration of illness, cognitive impairment, overall severity of illness, or neuropsychological findings. Patients with the Lewy body variant of Alzheimer's disease tended to experience more frequent extrapyramidal side effects of neuroleptics than did the patients with Alzheimer's disease, but for patients in the two groups who were not exposed to neuroleptics, there was little difference in frequency of extrapyramidal side effects. CSF concentration of homovanillic acid (HVA) was significantly lower in the Lewy body variant patients, even when correction was made for height. CONCLUSIONS: The Lewy body variant of Alzheimer's disease may be suspected in elderly male dementia patients who otherwise meet criteria for Alzheimer's disease but who manifest significant psychiatric symptoms and neuroleptic-induced extrapy-ramidal side effects and have low levels of CSF HVA.

Contribution of asymmetric synapse loss to lateralizing clinical deficits in frontotemporal dementias.

BACKGROUND: Synapse loss has been found to be the major correlate of cognitive decline in Alzheimer disease (AD), and prefrontal synapse loss has been found in patients with frontotemporal dementia (FTD). OBJECTIVE: To see if our hypothesis that within each FTD case, regional synapse loss would correlate with lateralizing neuropsychologic and neurobehavioral deficits would be correct. DESIGN: We analyzed synaptophysin as a marker for synapse loss in snap-frozen brain samples, using an enzyme-linked immunosorbent assay technique. Quantitative results were obtained by comparing patient data with a standard curve made by analyzing serial dilutions of a recombinant synaptophysin protein fragment. A board-certified neuropsychologist and a board-certified neurologist, both unaware of the synaptophysin results, determined areas of primary neuropsychologic and neurobehavioral dysfunction. Relationships between areas of primary dysfunction and synapse loss were analyzed using the binomial test. PATIENTS: Six cases of FTD, 28 cases of AD, and 16 nondemented control subjects. RESULTS: Five of 6 FTD cases had regional synaptophysins correlating with lateralizing frontal or temporal deficits. Three of 6 correlated in 2 or more regions. Although our results were higher than that expected based on a pure-chance mechanism (50% vs 34%), statistical significance was not attained. CONCLUSIONS: We found a trend for an association between synapse loss and lateralizing neuropsychologic and neurobehavioral deficits in FTD. Studies in larger numbers of FTD cases are planned with the goal of attaining statistically significant conclusions.

Altered amyloid protein processing in platelets of patients with Alzheimer disease.

BACKGROUND: beta-Amyloid peptide, the core component of neuritic plaques in brain areas in patients with Alzheimer disease (AD), is 1 cleavage product of the beta-amyloid precursor protein (APP) in neurons and platelets. Alternate cleavage products of intact 140- to 150-kd APPs in platelets include nonamyloidogenic 120- to 130-kd and 110-kd isoforms. The possible differential significance of these 2 isoforms, structurally similar to protease nexin II, is unknown. OBJECTIVE: To determine whether the ratio of the 120- to 130-kd APP isoform to the 110-kd APP isoform as processed in platelets correlates with the presence of AD and/or the apolipoprotein E4 (ApoE4) allele, which is a major risk factor for AD. SETTING: The Alzheimer Disease Center at The University of Texas Southwestern Medical Center at Dallas. METHODS: The APP isoforms were quantitated with the use of 2 different Western blot detection methods in platelets from 15 patients with AD and 19 control subjects in whom genotyping of apolipoprotein E was performed. RESULTS: The mean ratio of the 120- to 130-kd APP isoform to the 110-kd APP isoform in the patients with AD was significantly lower than that of the control subjects (5.98 vs 7.64; P = .03 [method 1] and 5.98 vs 7.92; P = .01 [method 2]) after adjusting for age and the increased incidence of ApoE4 in patients with AD. The lower APP ratios were also associated with increased age and with the presence of an ApoE4 allele. CONCLUSIONS: The APP processing in platelets of patients with AD is different from that of control subjects. This difference, largely caused by factors other than the ApoE4 genotype, may reflect chronic platelet activation in patients with AD. The use of these data to estimate "AD risk," by using the APP isoform ratio, indicates an odds ratio of 1.75, suggesting possible utility as an adjunct in the diagnosis of AD. Moreover, these findings may relate to analogous alterations in APP processing that may occur in brain areas affected by AD.

Genetic factors for the development of Alzheimer disease in the Cherokee Indian.

OBJECTIVE: To study the relationship between the genetic degree of Cherokee ancestry, the apolipoprotein E *E4 (APOE*E4) allele type, and the development of Alzheimer disease (AD) in individuals from the Cherokee Nation who reside in northeastern Oklahoma. SETTING: Alzheimer disease center satellite clinic and university departments of neurology, psychiatry, and academic computing. DESIGN: Standardized dementia evaluations based on criteria from the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association were performed on 26 patients aged 65 years or older to establish a diagnosis of AD. Twenty-six control subjects were recruited and similarly assessed. The APOE allele type determinations were obtained on all patients and control subjects. Appropriate statistical analyses were used to compare the genetic degree of Cherokee ancestry, the APOE allele type, and the development of AD. RESULTS: The data indicated that as the genetic degree of Cherokee Indian ancestry increased, the representation of AD decreased. The 9 patients with AD with a greater than 50% genetic degree of Cherokee ancestry constituted 35% of the group with AD. The 17 remaining patients with AD who were less than 50% Cherokee constituted 65% of the group with AD. In contrast, 17 (65%) of the control subjects were more than 50% Cherokee; only 9 (35%) were less than 50% Cherokee. These percentages of AD were not changed by the *E4 allele. This inverse relationship between the genetic degree of Cherokee ancestry and AD, independent of the APOE*E4 allele status, diminished with increasing age, suggesting an age-related protective effect of being Cherokee. For a decrease of 10% in Cherokee ancestry, the odds of developing AD are estimated to be 9.00 times greater at age 65 years but only 1.34 times greater at age 80 years. CONCLUSIONS: A greater genetic degree of Cherokee ancestry reduces the risk of developing AD and, thus, seems protective. This protective genetic factor is independent of APOE allele type and diminishes with age.

Platelet APP isoform ratios correlate with declining cognition in AD.

BACKGROUND: Platelets and neurons both contain large quantities of two carboxyl-truncated 120 to 130 and 110 kDa Alzheimer amyloid precursor proteins (APPs). Platelets taken from patients with AD have been reported to contain a reduced ratio of these APPs. OBJECTIVE: To further study the AD specificity of reduced platelet APP ratios and to determine whether, after 3 years, cognitive losses in AD are accompanied by similarly reduced platelet APP ratios. METHODS: To test the AD specificity of reduced platelet APP ratios, we quantitated these APPs in eight patients with PD and six patients with hemorrhagic stroke (HS). To determine whether further cognitive losses correlate with platelet APP ratio reductions in patients with AD, the authors re-examined platelet APPs and Mini-Mental State Examination (MMSE) scores of 10 patients with AD and 11 controls, who were tested 3 years ago. APP ratios were determined by the average of six assays using Western blotting with m22C11 monoclonal antibody, enhanced chemoluminescence, and digital scanning of autoradiographs. RESULTS: APP ratios were normal in the patients with PD and HS, further supporting the AD specificity of this assay. After 3 years, the MMSE scores and APP ratios of our control subjects changed by <4%. However, the average MMSE scores of our patients with AD declined from 16.4 to 8.3, and their average 120 to 130/110 kDa APP ratios declined from 5.8 to 3.6. The difference between AD and control APP ratios, with no overlap, is significant and the correlation between the 3-year decline in AD MMSE scores and reduced APP ratios (r = 0.69) was significant. CONCLUSIONS: Although the number of subjects analyzed was limited, reduced platelet APP ratios appear to be a specific biological marker of AD and a biological index of the severity of cognitive loss in AD.

Reduced platelet cytochrome c oxidase activity in Alzheimer's disease.

We evaluated a simplified method for preparation and analysis of platelet cytochrome c oxidase activity in Alzheimer's disease (AD) and control patients. Mean cytochrome c oxidase activity in controls (n = 17) was 0.233 sec-1/mg whereas mean cytochrome c oxidase activity in Alzheimer patients (n = 19) was 0.193 sec-1/mg, p = 0.033. Complex III (ubiquinol:cytochrome c oxidoreductase), complex II (succinic dehydrogenase), and citrate synthase were all assayed as internal controls and were not significantly different in controls and Alzheimer patients. There is a relatively specific loss of platelet cytochrome c oxidase activity in Alzheimer disease patients.

Clinical presentation of late-onset schizophrenia.

DSM-III-R defines late-onset schizophrenia as schizophrenia that begins after age 45. The authors describe five patients who met DSM-III-R criteria for this disorder. The characteristic features of the disorder include bizarre delusions (usually of a persecutory nature), auditory hallucinations, a history of normal functioning at least until age 45, and a deterioration in personal-social functioning after the onset of illness. Physical examination, routine laboratory tests, neuropsychological evaluation, and magnetic resonance imaging (MRI) scans did not suggest the presence of any diagnosable organic mental disorder. In each of the five cases, mood disorders, delusional (paranoid) disorder, and schizophrenia with onset before age 45 were also considered in the differential diagnosis and ruled out. The authors' case vignettes support the premise that late-onset schizophrenia is a clinically diagnosable entity. Cautions in the diagnosis and treatment of such patients are discussed.

Neuropsychological dysfunction in parents of schizophrenics.

Neuropsychological measures designed to examine aspects of attention, learning efficiency, and memory were investigated in 14 schizophrenic probands, their 28 parents, and 18 normal individuals. Probands performed at levels significantly below normals on measures of attention and of learning efficiency and performed below their parents on a subset of the same measures. Eight families had one parent with a personal or ancestral pedigree history consistent with schizophrenia; the other parent's personal and ancestral history was negative for schizophrenia. In these families, the probands were significantly different from the negative-history parents, but not the positive-history parents on an aggregate index of attention. Schizophrenics were significantly different from both the positive- and negative-history parents on an aggregate index of learning efficiency. These results extend previous findings of specific neuropsychological dysfunction in attention and learning in schizophrenics to show that some of the deficits are present in a subgroup of their parents, those who are likely carriers of genes conveying risk for schizophrenia. The data suggest that a heritable component of the neuropsychological deficit is a primary dysfunction in attention, and that a secondary or additional deficit in learning may be evident in family members who actually express the disorder of schizophrenia.

Neurophysiological and neuropsychological evidence for attentional dysfunction in schizophrenia.

The behavior of the P50 wave of the auditory evoked potential in a paired stimulus or conditioning-testing paradigm has been used as a measure of sensory gating disturbance in schizophrenia. Schizophrenics fail to decrement the P50 response to the second stimulus of the pair, so that the ratio of the test to the conditioning amplitude is elevated over normal values. The aim of this study was to compare this neurophysiological measure to neuropsychological measures of attention and memory. As expected, schizophrenics performed worse than controls on most measures. The time to complete a digit cancellation test, a measure of sustained attention, was found to be particularly longer in schizophrenics than in control subjects. Furthermore, the increased time to complete this task correlated with the increased ratio of the amplitude of the test P50 response to the conditioning response in the schizophrenics. Thus, a neurophysiological defect in sensory gating may relate to a disorder in sustained attention in schizophrenia. Although the P50 wave may come from the hippocampus, neuropsychological measures of verbal learning and memory were not correlated with alterations in the P50 ratio.

Neuropsychology of late-life psychoses.

The number of published neuropsychological studies of older psychiatric patients have been few. Moreover, almost nothing is known about the neuropsychological status of older individuals who develop psychotic symptoms for the first time later in life. Because of the spectrum of possible diagnostic considerations, careful diagnostic evaluations are of critical importance. Such evaluations should include comprehensive history-taking (using several sources), in addition to medical, psychiatric, neurologic, neuroimaging, and neuropsychological assessments. As the number of older individuals in our population grows, we will be increasingly faced with neuropsychiatric disorders that may arise de novo in the elderly. Multimodal and longitudinal investigations of older patients who develop psychotic or depressive symptoms are needed.

Poststroke depression and psychosis.

Stroke is capable of producing a varied spectrum of neurobehavioral syndromes that may come to the attention of the mental health professional evaluating psychiatric symptoms in elderly individuals. The neurobehavioral effects may include affective or psychotic symptoms and may occur immediately after the stroke or months to years later. The presence of underlying (or pre-existing) brain disease may have an adverse effect on the resolution of the neuropsychiatric symptoms. Although there are no treatment response studies in the area of psychosis following stroke, the response of poststroke depression to antidepressants makes attempted pharmacologic treatment of symptoms justified.

Neuropsychological test performance and MEG-based brain lateralization: sex differences.

Magnetoencephalographic (MEG) auditory evoked fields (EF) were recorded from left and right hemispheres of 9 normal males and 12 normal females. Source location of the 100 ms latency component (M100) was localized to superior temporal lobes bilaterally using an inverse solution algorithm. All subjects also were administered the Wechsler block design and visual reproduction subtests, and the California Verbal Learning Test (CVLT). M100 source locations demonstrated significant sex differences in interhemispheric asymmetry. Males had source locations further anterior than females, with the differences most pronounced in the right hemisphere. Expected sex differences were found in neuropsychological test performance, with males performing better on block design ad visual reproduction, and females performing better on the CVLT. Across both sexes, block design scores correlated significantly with right hemisphere M100 location, with more anterior source locations associated with better performance. CVLT scores were negatively correlated with right hemisphere M100 source locations. These findings suggest MEG-based measures of interhemispheric asymmetry may be related to specific neuropsychological test performance measures.

Clinical outcome of unilateral stereotactic pallidotomy without microelectrode recording for intractable Parkinson's disease.

OBJECTIVE: To study the effects of unilateral stereotactic pallidotomy performed without microelectrode recording for advanced Parkinson's disease. METHODS: Stereotactic coordinates were calculated by comparing preoperative inversion recovery MRI sequences with intraoperative CT scans. Conventional stereotactic stimulation techniques were employed to confirm correct probe placement. Patients were assessed using a modified CAPIT protocol with the off-state UPDRS motor score as the primary efficacy measure. RESULTS: A statistically significant decline in off-state UPDRS motor scores occurred at 2months (21% improvement in 32 patients) and also at 1year postoperatively (30% improvement in 12 patients). Levodopa-induced dyskinesias on the side contralateral to surgery were reduced 97% in the cohort with 1year of follow-up. No deleterious effects of surgery on global neuropsychological functioning were seen. A major surgical complication (mild but persistent hemiparesis) occurred in one patient. CONCLUSIONS: We believe that stereotactic pallidotomy can be performed safely and effectively without microelectrode recording when coordinates are calculated using CT with comparison to preoperative MRI sequences.

Schizophrenia and nicotinic receptors.

Patients with schizophrenia often cannot respond to important features of their environment and filter out irrelevant stimuli. This dysfunction could be related to an underlying defect in inhibition--i.e., the brain's ability to alter its sensitivity to repeated stimuli. One of the neuronal mechanisms responsible for such inhibitory gating involves the activation of cholinergic nicotinic receptors in the hippocampus. These receptors are diminished in many specimens of hippocampal brain tissue obtained postmortem from schizophrenic patients. In living schizophrenic patients, stimulation of cholinergic receptors by nicotine transiently restores inhibitory gating of evoked responses to sensory stimuli. Many people with schizophrenia are heavy smokers, but the properties of the nicotinic receptor favor only short-term activation, which may explain why cigarette smoking is only a transient symptomatic remedy. This paper reviews the clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function. Inhibitory gating deficits are only partly normalized by neuroleptic drugs and are thus a target for new therapeutic strategies for schizophrenia.

Early detection of fronto-temporal degeneration by clinical evaluation.

Although Alzheimer's Disease (AD) is the most common degenerative dementia, other neuropathological processes are well known to cause dementia syndromes. Fronto-temporal degeneration (FTD) is one such entity, and often produces a clinical presentation distinct from that of AD. Some FTD cases are shown at autopsy to be classic Pick's Disease, but others defy precise classification at this point because they lack characteristic Pick bodies. We describe a case of putative FTD in a 54-year-old man with personality change and complete Klüver-Bucy syndrome. Neuropsychological evaluation disclosed evidence of extensive frontal system dysfunction, with lesser problems in memory, language, and visuospatial skills. Magnetic resonance imaging studies after 17 months of the illness were largely nonspecific, but a follow-up scan 16 months later revealed bifrontal and bitemporal atrophy with ventricular enlargement. Neuromorphometric analysis suggested an increase in cortical atrophy and ventricular dilation over time. This case emphasizes the value of careful clinical evaluation in unusual non-AD degenerative dementias and suggests that neuroimaging studies may be less sensitive in the early diagnosis of such cases.