Pathological association and dissociation of functional systems in multiple sclerosis and Huntington's disease.

This study examined pathological associations and dissociations of functional cognitive systems in patients with multiple sclerosis and Huntington's disease. Using the subtests of the WAIS-R, two motor tests, and the word fluency test, the interest correlations showed distinct patterns. In comparison to normals, the two clinical groups exhibited a greater degree of association among the tests. Subsequently, word fluency performance was predicted from these tests. For the normals, the overall predictive power was quite low (7%). For the MS group, the predictive power rose to 28%. For the HD group, the predictive power was 50%. These results suggest that pathological association of functional systems may be a marker of brain dysfunction and that the affected systems may be delineated by these methods.

Models of cognitive deficit and statistical hypotheses: multiple sclerosis, an example.

The purpose of the current study was to describe four models of cognitive deficit and to outline the statistical hypotheses underlying each model. The four models of cognitive deficit were (a) specific deficit; (b) subgroup deficit; (c) a syndrome dissociation model; and (d) a global function dissociation model. Neuropsychological data are analyzed to examine each of these four models in a sample of mild Multiple Sclerosis (MS) patients. The results suggest that for these subjects and tests, the specific deficit model best fits the data. The results are reviewed initially in the context of MS. There follows a consideration of statistical caveats and finally, general applications of the proposed procedures.

Long-term outcome of head injuries: a 23 year follow up study of children with head injuries.

The purpose of the 23 year follow up study was to determine the relationship between trauma variables including measures of head injury and very long-term sequelae. The study included 159 individuals with a mean age 31.40 years, of whom approximately 90% were admitted to hospital with a mild head injury during childhood (mean age 7.96). Extent of head injury was determined by unconsciousness, neurological status, skull fracture, EEG, post-traumatic seizures and a composite measure. The composite measure of neurological variables was the best predictor of long-term outcome. In addition, IQ recorded in the post-acute phase was a reliable predictor of long-term outcome. Of the sample, 32.7% reported physical complaints and 17.6% reported current psychological/psychiatric problems unrelated to the head injury. Subjective sequelae (physical, intellectual and emotional) specified as due to the head injury were reported by 31% of the sample, and the sequelae were found to be related to the extent of the head injury and initial IQ. There were no discernible relationships between attribute variables including premorbid status and age with subjective sequelae. There were, however, significant relationships between subjective sequelae and objective, psychosocial measures of adaptation including educational lag, unemployment, current psychological/psychiatric problems and relationships with family members. Finally, there appeared to be continuity of complaints elicited during the five year follow up of the original project and current sequelae. The severity of the head injury was identified as the primary contributory factor in the reconstitution process and in the prediction of long term outcomes.

Ventricular size, cognitive function and depression in patients with multiple sclerosis.

The purpose of this study was to explore further the hypothesis that changes in cognitive function may occur in the mild stages of multiple sclerosis (MS) by determining whether ventricular enlargement was related to cognitive function. Ten measures of ventricular size were made in a sample of 123 MS patients with mild disability and 60 well-matched healthy controls. In addition, sixteen tests of cognitive function and the Beck Depression Inventory were administered. For the MS group, there were significant correlations between the ventricular measures and cognitive performance but not for the normal controls. Scores on the Beck Depression Inventory were not correlated with either cognitive performance or ventricular enlargement. These findings suggest that for the MS group cognitive impairment was related to the disease process but not to the level of depression.

Sleep disturbance, depression, and lesion site in patients with multiple sclerosis.

We examined the prevalence of sleep problems in a sample of patients with mild but clinically definite multiple sclerosis (n = 143) and sought to determine whether there was a relationship between the presence of sleep complaints and the level of depression. As magnetic resonance imaging scans were available for a subsample of the patients with multiple sclerosis (n = 117), we also wanted to determine whether there was a relationship between the site of the lesion and the presence of sleep difficulties. The prevalence of sleep difficulties was three times higher in the patients with multiple sclerosis than the control group (25.2% vs 8.2%). Moreover, the presence of sleep complaints was associated with higher levels of depression. Three lesion sites that subserve supplemental motor areas were significantly related to the presence of sleep complaints. These findings suggest that, for some patients with MS, sleep disturbance and accompanying increases in depression may be a function of the lesion site resulting in nocturnal spasms.

Empirical support for psychological profiles observed in multiple sclerosis.

Though increasing attention is being paid to psychological aspects of multiple sclerosis, much research continues to examine patients as differing in quantity rather than quality of psychological abnormality or response. Cluster analysis was used to identify distinctive psychological profiles in a large sample of patients with multiple sclerosis. It employed three measures, carefully chosen to capture the main responses historically observed in multiple sclerosis. These measures were (1) the patient's physical disability-impairment, assessed by a neurologist; (2) physical disability-impairment as perceived and reported by the patient; and (3) self-reported psychological well-being (or distress) independent of physical signs and symptoms. The optimal solution from the cluster analysis separated the 99 patients into 10 clusters, which were collapsed into four profiles, consistent with the labels "depression," "denial," "exaggerated somatic," and "severity-related." These data give strong empirical support to the existence of discrete and distinctive coping styles in multiple sclerosis.

Neuropsychological performance in patients with mild multiple sclerosis.

Although changes in cognitive function in patients with multiple sclerosis (MS) have been reported, these changes have been traditionally associated with the later stages of the disease. In the current study, a comprehensive neuropsychological battery was administered to MS patients (N = 86) in whom the disease progression was relatively mild and in remission and a demographically well-matched control group (N = 46). Besides the expected differences in tests of motor function, the two groups also differed on a number of cognitive tests with no motor demands. The two cognitive functions that appear impaired were learning and memory. Given that similar deficits have been found in MS patients with more severe symptoms, it is argued that changes in cognitive function can occur in the mild stages of the disease.

Regional cerebral glucose metabolism in major depressive disorder.

Six subjects with DSM-III defined unipolar major depressive disorder had positron emission tomography scans using 18F-2-fluoro-2-deoxy-D-glucose (2FDG) before and after treatment with imipramine. Their 12 scans were compared to the scans of six controls matched for age. Significant reductions in metabolism for subjects in the depressed group were found on scans for both the anterior and right frontal regions. significant reductions in metabolism occurred more often in the right hemisphere than the left. No significant changes in metabolism could be attributed to imipramine. In addition, absolute metabolic rates were not related to the degree of depression pre- and post-treatment. The findings suggest that hypometabolism in the frontal cortex and right hemisphere may occur in major depressive disorders.

Right and left orientation in children aged 5 to 13 years.

A 32-item test of right/left orientation was administered to 360 normal children, aged 5 to 13 years. The distribution of scores was tested to determine if parametric descriptive statistics were appropriate. As the distribution was multimodal, the test of normality was rejected. The three modes were consistent with a stage development theory, with the respective modes being consistent with (a) no understanding of right/left, (b) a personal or egocentric understanding of right/left, and (c) a generalization of right/left to external objects. Therefore, the data are presented in terms of the probability of obtaining a specific score at a given age. Scores were not found to be related to sex and were weakly, if at all, related to level of psychometric intelligence.

Regional cerebral glucose metabolism in Turner syndrome.

Regional cerebral glucose metabolism was examined in females with Turner syndrome, a sex chromosome abnormality. Previous studies have found a visual/spatial cognitive anomaly in these women but, to date, no abnormalities in brain structure or function have been associated with the condition. In the present study, decreases in regional metabolism were found in the occipital and parietal cortex. The involvement of the occipital cortex, although consistent with the observed cognitive anomalies, has not been suggested previously as an area dysfunction. Because the occipital cortex is a primary sensory cortex, the reduction of glucose metabolism in the parietal cortex may reflect a lack of innervation from the occipital cortex. Besides insight into the functional specialization of the brain, these findings are also consistent with previous reports on animals regarding the effects of estrogen in brain maturation.

Regional cerebral glucose metabolism in three sets of identical twins with psychotic symptoms.

Three sets of young identical twins where at least one had a psychotic episode were assessed in terms of psychiatric and psychological status and integrity of cerebral structure and metabolism. The psychiatric diagnoses for each set were normal/schizophrenia, prodromal/schizophrenia and schizoaffective/schizoaffective. The latter two sets were re-examined two years after the initial assessment. The data are considered from a case study perspective. Reduced cerebral metabolism was found for at least one region on eight of nine scans of patients with a psychotic history. On seven of the nine scans, glucose metabolism in the orbital frontal cortex was reduced. These findings are discussed with respect to previous studies of glucose metabolism in patients with schizophrenia, metabolic similarities found in normal identical twins and the known functional specialization of the orbital frontal cortex.

Two-year follow-up study of coronary bypass surgery. Psychologic status, employment status, and quality of life.

This study is a prospective report of the cases of 135 patients who were slated for coronary artery bypass grafting and selected according to designated criteria. Patients received, in addition to an interview, a comprehensive cognitive, neuropsychologic, and personality assessment 2 weeks before operation and 3, 12, and 24 months after operation. Of the available sample, 82.3% completed the full study. There was no evidence of intellectual or neuropsychologic impairment after operation. Most patients returned to preoperative status 3 months after bypass grafting. Further improvement may continue 12 and 24 months after operation. The personality tests revealed that anticipation of the operation resulted in signs of emotional arousal and distress, which dissipated after a successful surgical outcome. Similarly, return to work and quality of life was enhanced. The current study represents the first systematic, longer-term follow-up of the psychologic and social consequences of coronary artery bypass grafting operations. The findings of this study are discussed within a model of social reconstitution after the successful resolution of a life-threatening medical condition.

The role of prophylactic brain irradiation in limited stage small cell lung cancer: clinical, neuropsychologic, and CT sequelae.

Ninety-four patients with limited stage small cell lung cancer treated between 1981 and 1985 with a regimen including prophylactic brain irradiation (PBI) after combination chemotherapy were assessed for compliance with PBI, brain relapse, and neurologic morbidity. Seventy-seven percent of patients had PBI and of these, 22% developed brain metastases after a median time of 11 months post treatment. The brain was the apparent unique initial site of relapse in 10% of PBI cases but more commonly brain relapse was preceded or accompanied by failure at other sites, especially the chest. Brain metastases were the greatest cause of morbidity in 50% of PBI failures. Twelve of 14 PBI patients alive 2 years after treatment had oncologic, neurologic, and neuropsychological evaluation, and brain CT. All long-term survivors were capable of self care and none fulfilled diagnostic criteria for dementia, with three borderline cases. One third had pretreatment neurologic dysfunction and two thirds post treatment neurologic symptoms, most commonly recent memory loss. Fifty percent had subtle motor findings. Intellectual functioning was at the 38th percentile with most patients having an unskilled occupational history. Neuropsychologic impairment ratings were borderline in three cases and definitely impaired in seven cases. CT scans showed brain atrophy in all cases with mild progression in those having a pre-treatment baseline. Periventricular and subcortical low density lesions identical to the CT appearance of subcortical arteriosclerotic encephalopathy were seen in 82% of posttreatment CT studies, and lacunar infarcts in 54%. Neuropsychologic impairment scores and the extent of CT periventricular low density lesions were strongly associated (rank correlation 0.7, p less than .05). Overall, PBI after intensive combination chemotherapy did not induce gross dementia or neurologic dysfunction but its risk/benefit ratio is not overwhelmingly favorable, with failure to prevent brain relapse in 1/5 patients and subtle but detectable motor findings and neuropsychologic impairment in the majority.

Reliability and construct validity of the six-block Tactual Performance Test in and adult sample.

The ten-block Tactual Performance Test (TPT-10) has been criticized as a clinical instrument due to the long administration time and accompanying psychological distress. The shorter children's six-block version (TPT-6) has been proposed as a potential substitute. The current study examined the internal consistency, the test/retest reliability and the construct validity of the TPT-6. The results indicate that the TPT-6 is a very reliable instrument and is similar to the TPT-10 in terms of construct validity. Most importantly, the actual administration time is approximately one third that of the TPT-10.

Empirically derived MMPI profiles. Coronary bypass surgery.

A cluster analysis of eight clinical scales of the MMPI-168 was performed on data from 129 subjects awaiting coronary bypass surgery. Four abnormal profiles were derived and these profiles were consistent with clinical expectancy. The five empirically derived profiles were labeled as a) normal--that is, no elevated scales; b) marginal distress--elevated Hs; c) conversion V--elevated Hs and Hy; d) neurotic--elevated Hs, D, Hy, and Pt; and e) generalized distress--elevated D, Hy, Pd, Pa, Pt, and Sc. Subsequent postsurgical follow-ups were done at 3-, 12-, and 24-month intervals. These data suggest that the profiles retained their characteristic shape and were still statistically different from each other, but the overall elevation decreased significantly after successful surgical intervention. To externally validate these profiles, the five derived groups were compared in terms of Beck Depression scores and the State/Trait Anxiety Inventory. These results were consistent with the MMPI. These data are discussed in terms of developing models for assessing the interaction of personality and specific stressors.

Regional cerebral glucose metabolism in identical twins.

The present study reports on the degree of similarity in regional cerebral glucose metabolism in seven sets of female identical twins. All scans were done with subjects at rest. Glucose metabolism was measured with positron emission tomography (PET). Significant intraclass correlations were found for the orbital and prefrontal cortex as well as the basal ganglia (caudate/putamen). It is suggested that these correlations reflect the functional aspects of these areas, namely attention and posturing movements.

Treatment outcome of obstructive sleep apnea. Physiological and neuropsychological concomitants.

This study examines the cognitive and emotional changes associated with successful surgical treatment of patients with obstructive sleep apnea (OSA). By comparing the OSA patients with patients undergoing coronary artery bypass surgery before (2 weeks) and after (3 months) surgical intervention on a comprehensive psychological battery, it was determined that both groups exhibited anxiety and depression before surgery and these elevations (MMPI) were significantly lower after surgery. However, no differences were found between groups on any emotional or cognitive variable before or after surgical treatment.

Handedness concordance and intelligence discrepancies in identical twins.

The purpose of this study was to determine if the discrepancy in measured intelligence between identical twins concordant for handedness differed measureably from the discrepancy between identical twins discordant for handedness. If handed concordant and discordant twins did differ in terms of the between twin discrepancy in measured intelligence, then one could infer that congenital factors had caused dissociation of handedness and measured intelligence within a twin set. This finding would support Nagylaki and Levy's contention that the found discordance rates for handedness in identical twins is a function of "pathogenic" congenital factors disrupting the genetically determined handedness pattern. More generally, this finding would also support Satz's model with respect to pathological shifts in handedness due to brain insult either in utero or perinatally. However, in the current study, eight sets of identical twins were examined and no evidence was found to support these hypotheses. Instead, in one set where there was a marked discrepancy in measured intelligence, handedness could not be determined precisely for the twin with the lower intelligence quotient.

Cluster analysis of the WAIS on brain-damaged patients.

In recognition of increased usage of cluster analytic techniques, the current study attempted to examine sampling bounds for tests and subjects on one cluster-analytic procedure. Specifically, the WAIS subtest scores from a heterogeneous group of subjects with CNS involvement were first, factor analyzed and then clustered by means of Ward's hierarchical procedure. This methodology had been previously applied to two different samples of aphasics and aphasia batteries. In both these aphasic studies, an underlying severity dimension of language dysfunction was found. In contrast, in the current study, salient feature groups were found. Moreover, these groups were distributed in a sequential or hierarchical model in terms of specific cognitive deficits. From these data, it is argued that two major parameters in determining the resulting cluster structures are the homogeneity/heterogeneity of the sample and test battery employed. Although such a statement is obvious, the theoretical ramifications are large, in that the cluster structure may be a function of test weighting or sample diversity, not the phenomenon of interest. However, the cluster structures found in the current study were consistent with historical models of cognitive dysfunction and also lend support to hierarchical models of sequential cognitive impairment. These findings are discussed in terms of their clinical and experimental ramifications with respect to grouping subjects in terms of WAIS profiles.