Shawn D. Gale

MRI, quantitative MRI, SPECT, and neuropsychological findings following carbon monoxide poisoning.

Carbon monoxide (CO) poisoning has been shown to result in neuropathologic changes and cognitive impairments due to anoxia and other related biochemical mechanisms. The present study investigated brain-behaviour relationships between neuropsychological outcome and SPECT, MRI, and Quantitative magnetic resonance imaging (QMRI) in 21 patients with CO poisoning. Ninety-three per cent of the patients exhibited a variety of cognitive impairments, including impaired attention, memory, executive function, and mental processing speed. Ninety-five per cent of the patients experienced affective changes including depression and anxiety. The results from the imaging studies revealed that 38% of the patients had abnormal clinical MRI scans, 67% had abnormal SPECT scans, and 67% had QMRI findings including hippocampal atrophy and/or diffuse cortical atrophy evidenced by an enlarged ventricle-to-brain ratio (VBR). Hippocampal atrophy was also found on QMRI. SPECT and QMRI appear to be sensitive tools which can be used to identify the neuropathological changes and cerebral perfusion defects which occur following CO poisoning. Cerebral perfusion defects include frontal and temporal lobe hypoperfusion. Significant relationships existed between the various imaging techniques and neuropsychological impairments. The data from this study indicate that a multi-faceted approach to clinical evaluation of the neuropathological and neurobehavioural changes following CO poisoning may provide comprehensive information regarding the neuroanatomical and neurobehavioural effects of CO poisoning.

Fornix degeneration and memory in traumatic brain injury.

Fornix-to-brain ratios (FBR) based on postinjury magnetic resonance (MR) studies were calculated on a group of 27 female traumatic brain injury (TBI) patients and 18 female medical controls by taking the widest aspect of the fornix at the level of the anterior horns and third ventricle and determining a fornix surface area. The FBR was significantly reduced in the TBI group (FBR = 0.1121) as compared to the normal control group (FBR = 0.1766). Despite these significant FBR findings indicating prominent atrophic changes of the fornix in TBI patients, the FBR did not relate systematically to neuropsychological outcome. These findings clearly indicate fornix vulnerability in TBI and that current quantitative MR methods are sensitive enough to detect such changes. However, fornix degeneration constitutes only one of many contributing factors to the anatomic basis of TBI-induced cognitive disturbances, as fornix atrophy did not relate systematically to neuropsychological outcome.

Severe anoxia with and without concomitant brain atrophy and neuropsychological impairments.

Significant anoxia may cause a variety of neuropathologic changes as well as cognitive deficits. We have recently seen 3 patients who have suffered severe anoxic episodes all with initial Glasgow Coma Scores (GCS) of 3 with sustained coma for 10-14 d. All 3 patients had extended hospitalizations and rehabilitation therapy. A neuropsychological test battery was administered and volumetric analyses of MRI scans were carried out in each case at least 6 mo postinjury. Two of the patients display distinct residual cognitive and neuropathologic changes while 1 patient made a remarkable recovery without evidence of significant morphological abnormality. These three cases demonstrate, that even with similar admission GCS, the outcome is variable and the degree of neuropsychological impairment appears to match the degree of morphologic abnormalities demonstrated by quantitative MR image analysis. An important finding of this study is that even though subjects with an anoxic insult exhibit severe cognitive and memory impairments along with concomitant morphologic changes, their attention/concentration abilities appear to be preserved. MR morphometry provides an excellent means by which neural structural changes can be quantified and compared to neuropsychological and behavioral outcomes.

Traumatic brain injury, alcohol and quantitative neuroimaging: preliminary findings

Magnetic resonance (MR) quantitative neuroimaging analysis was undertaken with a large group of normal (n = 197) and traumatically brain injured (TBI, n = 99) adults. Of the TBI subjects 18 patients were identified with a history of substance-related abuse (TBI/Abuse group). Both the TBI/ Abuse group and the remaining sample of TBI patients (n = 81, TBI/Non-abuse group) without a history of substance-related abuse differed significantly from the control group on most quantitative MR imaging analyses. The TBI/Abuse group displayed the greatest degree of atrophic change. However, the TBI/Abuse group had a significantly lower Glasgow Coma Scale (GCS) score, ostensibly suggesting that those with substance-related abuse suffered more severe brain injury than non-abuse TBI patients. When a subset (n = 18) of the TBI/Non-abuse group was matched by GCS, gender and age to the TBI/Abuse group, both groups differed significantly from the control group on most morphometric measures, but did not differ from one another. Results are discussed in terms of the potential adverse role that substance-related abuse, particularly alcohol, plays in the individual who sustains traumatic injury to the brain.

Day of injury CT scan as an index to pre-injury brain morphology

This study compared the ventricle-to-brain ratio (VBR) of the day-of-injury (DOI) computerized tomogram (CT) in traumatic brain-injured (TBI) patients with post-injury (2 months or greater) magnetic resonance (MR) VBRs in the same patients and in medical control subjects. The DOI VBR did not differ significantly from the medical controls, but both (DOI and medical control VBR) differed significantly from post-injury VBR. Additionally, a case study is presented wherein MR imaging studies were obtained prior to TBI so that a direct comparison of pre-injury to DOI to post-injury changes could be made. In this case the pre-injury and DOI VBRs were within approximately 9% of each other. In contrast, the post-injury VBR demonstrated over a 100% increase in comparison to either the pre-injury or DOI scan. This case and another case are illustrated using three-dimensional image analysis to represent ventricular change over time. These cases, along with the similarity of the DOI VBR with the medical controls, suggests that the DOI VBR can be utilized as an estimate or index of pre-injury ventricle/brain morphology. This will permit the use of DOI CT data for within-subject designs in TBI research that examines the course of degenerative changes over time.

Association between latent toxoplasmosis and cognition in adults: a cross-sectional study

Latent infection from Toxoplasma gondii (T. gondii) is widespread worldwide and has been associated with cognitive deficits in some but not all animal models and in humans. We tested the hypothesis that latent toxoplasmosis is associated with decreased cognitive function in a large cross-sectional dataset, the National Health and Nutrition Examination Survey (NHANES). There were 4178 participants aged 20-59 years, of whom 19.1% had IgG antibodies against T. gondii. Two ordinary least squares (OLS) regression models adjusted for the NHANES complex sampling design and weighted to represent the US population were estimated for simple reaction time, processing speed and short-term memory or attention. The first model included only main effects of latent toxoplasmosis and demographic control variables, and the second added interaction terms between latent toxoplasmosis and the poverty-to-income ratio (PIR), educational attainment and race-ethnicity. We also used multivariate models to assess all three cognitive outcomes in the same model. Although the models evaluating main effects only demonstrated no association between latent toxoplasmosis and the cognitive outcomes, significant interactions between latent toxoplasmosis and the PIR, between latent toxoplasmosis and educational attainment, and between latent toxoplasmosis and race-ethnicity indicated that latent toxoplasmosis may adversely affect cognitive function in certain groups.

Neuropsychological outcome following minimal access subtemporal selective amygdalohippocampectomy

PURPOSE The present study provides a detailed account of neurocognitive outcome following minimal access subtemporal selective amygdalohippocampectomy (SAH) and establishes rates of neurocognitive decline in the largest sample to date. Use of a subtemporal surgical approach to SAH has been proposed to possibly reduce the risk for postoperative neurocognitive decline since lateral neocortical tissues is not resected and the temporal stem is preserved. The current study extends prior research with subtemporal SAH patients to include not only group level analyses but also analyses based on reliable change data. METHODS Neurocognitive comparisons are made between 47 patients that underwent subtemporal SAH. Statistical comparisons were made between neurocognitive performance at the group level and with use of reliable change scores. RESULTS Approximately 75% of patients were seizure free postoperatively. At the group level, there were no significant postoperative changes. For the left SAH patients, reliable change scores demonstrated a decline in approximately one third of patients for memory, verbal intellect, and naming. Right SAH patients showed decline primarily in memory. CONCLUSIONS These results indicated good seizure control following subtemporal SAH with greatest risk for neurocognitive decline following dominant SAH and best cognitive outcome following non-dominant SAH. Findings demonstrated the importance of reliable change analyses that make individual based comparisons and take into account measurement error. Despite preservation of the lateral neocortical tissue and the temporal stem, subtemporal SAH presents a risk for cognitive decline in a notable portion of patients.

APOE ε4 is associated with exacerbation of cognitive decline in patients with multiple sclerosis.

Background: In previous studies we and others have demonstrated an association with apolipoprotein (APOE) &egr;4 genotype and the presence of cognitive deficits in multiple sclerosis (MS). In this follow-up study, we have assessed whether APOE &egr;4 status exacerbates progression of cognitive deficits in MS. Methods: A total of 197 patients with MS were assessed for APOE genotype, and baseline cognitive performance was measured using a standardized battery of tests. One hundred seventy patients (86.3%) were clinically followed up for 1 year and were assessed for progression of cognitive deficits. Results: The APOE &egr;4 allele was present in 24.7% of patients. During 1-year follow-up, significant progression of cognitive deficits was found in APOE &egr;4 carriers (P=0.001) after logistic regression analysis controlling for sex, ethnicity, age, education, disease duration, severity, and subtype. Conclusions: APOE &egr;4 carriers with MS have worsening progression of cognitive deficits than noncarriers. APOE &egr;4 carrier status predicts cognitive decline in verbal learning and memory.

Concurrent administration of the MMPI-2 and PAI in a sample of patients with epileptic or non-epileptic seizures: implications for an inpatient epilepsy monitoring unit.

The Minnesota Multiphasic Personality Inventory-second edition (MMPI-2) and the Personality Assessment Inventory (PAI) are commonly used in the epilepsy monitoring unit (EMU) to evaluate personality characteristics and mood-related symptoms in those individuals being evaluated for epileptic seizures (ES) or psychogenic non-epileptic seizures (PNES). A direct comparison of these measures through concurrent administration to the same group has not been carried out. Both measures were administered to 40 patients (17 ES and 23 PNES). Logistic regression suggested the optimal predictive model for EMU discharge diagnosis included subscales from each measure, which outperformed either measure separately. Combining the conversion (SOM-C) and health concerns (SOM-H) subscales from the PAI and the hysteria subscale (Hy) from the MMPI-2 resulted in 85% overall classification accuracy, 86.7% sensitivity, and 82.4% specificity. Variability in the literature regarding the predictive utility of these measures may stem from the possibility that they measure different aspects of PNES.

Infectious disease burden and cognitive function in young to middle-aged adults

Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults.