Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings.

BACKGROUND AND OBJECTIVES: We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. METHODS AND RESULTS: Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. CONCLUSIONS: Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry.

Neuropsychological impairment in Parkinson's disease with and without depression.

OBJECTIVES: To compare quantitative and qualitative aspects of neuropsychological test performance in patients with Parkinson's disease who currently had depression (PDD) and those without depression (PDN) so as to evaluate the influence of depression on cognition in Parkinson's disease. DESIGN: Cross-sectional comparisons among PDN, PDD, and normal control (NC) groups. The setting was a neurodegenerative disease research center in a teaching hospital. Groups consisted of 44 patients with PDN and 44 patients with PDD matched for age, education, gender, age at onset of disease, disease duration, and disease severity; a group of 44 NC subjects matched for age, education, and gender; and a second set of comparisons between 15 patients with PDN and 15 patients with PDD also matched for overall severity of cognitive impairment. MEASURES: The neuropsychological measures used were the Mattis Dementia Rating Scale, Beck Depression Inventory, Wisconsin Card Sorting Test, Controlled Oral Word Association Test, Logical Memory subtest of the Wechsler Memory Scale-Revised, Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised, and the Boston Diagnostic Aphasia Examination's Animal Naming test and Boston Naming Test. RESULTS: Relative to the NC group, both PDN and PDD groups demonstrated impairments in immediate and delayed verbal recall, semantic fluency, and problem solving. When PDN and PDD groups were matched for demographic and disease variables, only the PDD group evidenced impairment relative to NC in visual confrontation naming, and in lexical and semantic fluency. In addition, impairments on immediate recall and semantic fluency in the PDD group were more pronounced than those in the PDN group. However, when PDN and PDD groups were also matched for overall severity of cognitive impairment, no significant differences emerged among the two groups' neuropsychological test performances. CONCLUSIONS: Depression exacerbates some memory and language impairments associated with PD, even when the PDN and PDD groups are matched for demographic and disease variables. However, the extent and pattern of cognitive impairment is similar in PDN and PDD when the groups are also matched also for overall severity of cognitive impairment. Depression influences the quantity rather than the quality of cognitive impairment associated with Parkinson's disease.

Unilateral pallidal stimulation for Parkinson's disease: neurobehavioral functioning before and 3 months after electrode implantation.

Unilateral pallidotomy is thought to have a low risk for cognitive morbidity. Nonetheless, recent research suggests that some patients experience declines in memory and language and that pallidal stimulation might be a safer treatment for Parkinson's disease (PD). We investigated the neurobehavioral effects of unilateral pallidal stimulation. Nine consecutive PD patients undergoing unilateral deep brain-stimulating electrode implantation in the globus pallidus interna were evaluated with a neuropsychological test battery approximately 1 month before and 3 months after surgery. Patients reported significantly fewer symptoms of anxiety and greater vigor after surgery. There was a trend toward fewer depressive symptoms. Semantic verbal fluency and visuoconstructional test scores declined significantly after surgery. However, among five patients showing declines in semantic verbal fluency, only one patient's score declined by more than 2 SD. No patient showed significant decline or improvement in the overall level of cognitive functioning. This study supports the relative safety, in terms of cognitive function, of unilateral pallidal stimulation in PD.

Neuropsychological and quality of life outcome after thalamic stimulation for essential tremor.

OBJECTIVE: To evaluate short-term effects of unilateral thalamic deep brain stimulation (DBS) on cognition, mood state, and quality of life in patients with essential tremor (ET). BACKGROUND: Unilateral thalamotomy and thalamic DBS are effective in alleviating refractory tremor contralateral to the side of surgery. Thalamotomy can lead to cognitive morbidity, and DBS might be a preferable surgical intervention given potential avoidance or reversibility of such morbidity. Although unilateral thalamic DBS is cognitively safe and leads to quality of life improvement in PD, its neurobehavioral effects in ET are unknown. METHODS: Forty patients with ET were administered a broad neuropsychological test battery, measures of mood state, and generic and disease-specific quality of life measures approximately 1 month before and 3 months after surgery (left hemisphere, 38 patients). RESULTS: Unilateral thalamic DBS was associated with significant improvements in tremor and dominant-hand fine visuomotor coordination. Statistically significant but clinically modest gains were observed on tasks of visuoperceptual and constructional ability, visual attention, delayed word list recognition, and prose recall. Only lexical verbal fluency declined significantly after surgery. Patients rated themselves as less anxious after surgery, and they perceived their quality of life as improved significantly. In particular, patients reported improved quality of life with respect to activities of daily living, stigma, emotional well-being, and communication. CONCLUSIONS: Unilateral thalamic DBS for ET is cognitively safe and associated with improvements in anxiety and quality of life in the near term and in the absence of operative complications. Patients were better able to carry out activities of daily living after surgery, and they reported improvement in several psychosocial domains of quality of life.

Action (verb naming) fluency as an executive function measure: convergent and divergent evidence of validity.

Numerous studies have demonstrated dissociable neuroanatomic underpinnings for the retrieval of grammatical classes of words such as nouns and verbs. Whereas retrieval of common and proper nouns is primarily mediated by posterior and anterior temporal regions, respectively, verb retrieval is primarily mediated by frontal regions. The majority of studies evaluating verb production have utilized tasks requiring subjects to name a graphically depicted action (i.e. action naming), leaving tests of verb generation in the absence of prompting stimuli (i.e. action fluency) largely unexamined. In a recent study, Piatt, Fields, Paolo, Koller and Tröster (in press) found that an action fluency task discriminated demented Parkinson's disease (PD) patients from non-demented PD patients and healthy control subjects, whereas lexical and categorical fluency tasks did not. These authors suggested that action fluency was sensitive to the fronto-striatal pathophysiology associated with PD dementia, and thus, that action fluency might serve as an indicator of executive functioning. This study was undertaken to evaluate the construct validity of action fluency as an executive function measure in a group of healthy elderly control subjects. Findings revealed modest to moderate relationships between action fluency and several putative executive measures. Action fluency was unrelated to indices of semantic and episodic memory. Results support the construct validity of action fluency as an executive function measure and suggest that this task may provide some unique information not tapped by traditional executive function tasks.

Cortical and subcortical influences on clustering and switching in the performance of verbal fluency tasks.

Impairments on lexical and semantic fluency tasks occur in both cortical and subcortical dementia. Recent reports that the average size of phonemic and semantic clusters is reduced in Alzheimer's disease (AD), but not in Parkinson's disease (PD) could support the hypothesis that in AD verbal fluency deficits arise from degraded memory storage while in PD the same impairments result from defective retrieval. In the present study, patients with AD, PD with dementia, or Huntington's disease produced fewer words, fewer switching responses and smaller semantic cluster sizes. Patients with multiple sclerosis, regardless of whether or not they were demented, produced fewer words and switching responses, but normal size clusters, and patients with PD without dementia performed normally on all fluency measures. These results indicate that reductions in cluster size on verbal fluency tests are best interpreted as changes in the efficiency of access to lexical and semantic memory stores. The findings are also consistent with the idea that patterns of cognitive impairment may differ among diseases that result in subcortical dementia.

Cognitive outcome following staged bilateral pallidal stimulation for the treatment of Parkinson's disease.

As neurosurgical treatment of parkinsonian symptoms has become increasingly popular, concern about the cognitive morbidity which may result from such interventions has risen proportionately. Previous reports of cognitive difficulties associated with pallidotomy and thalamotomy, especially in bilateral cases, have provided the impetus for research into chronic electrical deep brain stimulation procedures which are believed to be safer than ablation. Given the lack of neurobehavioral research following bilateral deep brain stimulation procedures, this preliminary study of six Parkinson's disease patients undergoing staged bilateral pallidal stimulation was undertaken. A battery of tests assessing attention, executive function, visuomotor coordination, language, visuoperceptual function, learning memory and mood revealed no significant change in overall level of cognitive functioning after either unilateral or bilateral pallidal deep brain stimulation. No significant declines were observed about three months following bilateral stimulation, and in fact, significant gains in delayed recall and relief of anxiety symptoms were noted. It was concluded from this preliminary data that bilateral pallidal stimulation for the treatment of Parkinson's disease, at least in the absence of operative complications, offers a cognitively safe alternative to ablation.

Frontal cognitive function and memory in Parkinson's disease: toward a distinction between prospective and declarative memory impairments?

Memory dysfunction is a frequent concomitant of Parkinson's disease (PD). Historically, two classes of hypotheses, focusing on different cognitive mechanisms, have been advanced to explain this memory impairment: one postulating retrieval deficits (common to several neurodegenerative disorders involving the basal ganglia), and the other postulating frontally mediated executive deficits as fundamental to memory impairment. After outlining empirical support for the retrieval deficit hypothesis, research on the more recent "frontal executive deficit hypothesis" is reviewed, and major challenges to this hypothesis are identified. It is concluded that the frontal executive deficit hypothesis cannot adequately account for all memory impairments in PD, and that a more parsimonious theoretical account might invoke a distinction between prospective and declarative memory impairments. It is suggested that there may be three subgroups of PD patients: one demonstrating prospective memory dysfunction only, one with declarative memory dysfunction only, and one with both prospective and declarative memory dysfunction. Consequently, PD might provide a useful model within which to investigate the relationship between prospective and declarative memory.

Semantic fluency performance of patients with cortical and subcortical neurodegenerative diseases.

Previous studies using the Animals Fluency Test have shown that dementia patients with Alzheimer's disease (AD), Huntington's disease (HD), or Parkinson's disease (PD) produce fewer correct words and have smaller semantic cluster sizes than controls or PD patients without dementia (PDND). Although the number of correct words generated by the patients with AD was positively correlated with mental status, cluster size, surprisingly, was not. To increase word output and increase the reliability of estimates of cluster size, semantic fluency was reexamined using the Supermarket Fluency Task. Overall, patients with HD or PD with dementia (PDD) exhibited reduced cluster sizes compared to older controls or PDND patients, but cluster sizes were only marginally reduced for patients with AD. These effects were evident only for female participants, because the cluster sizes for elderly control men were substantially smaller than those of elderly women. For the female patients with AD, cluster size was correlated with mental status, but the relationship was nonlinear. Cluster size was normal for mildly demented patients with AD, but much reduced for moderately or severely demented participants. In contrast to a previous report, in the present study the proportion of category labels generated was increased for patients with HD with dementia but not for patients with AD. This finding questions one line of evidence that semantic memory stores undergo "bottom-up" degradation in AD. Together with previous results, these findings indicate that semantic cluster size reflects efficiency of access to semantic knowledge which is similarly compromised in subcortical and cortical diseases.

Why small businesses don't have health insurance: results of a Florida survey.

While most of the insured population has health insurance under an employer-sponsored group plan, the majority of the working uninsured are employed by small firms. Increasing the number of small firms that provide health insurance plans to their employees is important for decreasing the number of uninsured. This article summarizes the results of a survey designed to study characteristics of the firms that do not have health insurance, the obstacles to their getting insurance, and small business owners' interest in having a group health plan.

Regulating managed care firms: the Connecticut plan.

Virtually every state in the country, as well as the federal government, is either considering or has recently considered legislation to regulate utilization review/managed care companies. Despite the magnitude of this issue, few legislative bodies have expended the resources to study the form that regulation should take. Recently, Connecticut, which has seen considerable growth in utilization review within managed care programs that insure Connecticut residents, funded such a study. This article, authored by two of the study's participants, reviews the issues and explains the study's recommendations.

Regulating health insurance: the challenges of managed networks.

The role of the regulator in health insurance is examined in the context of the change in nature of regulatory oversight necessary to monitor the activities of the regulated parties. Health insurance to this point has been largely regulated by insurance departments that have historically focused on monitoring the solvency and meeting the contractually required reimbursements for indemnity carriers. Now as the indemnity carrier has either migrated to managed care or faced a declining book of business, the historic role of regulation must change to match the new environment. This article examines the role of the health insurance/managed care regulator department under this new paradigm and identifies where and how the regulator can exert influence in such a system.

Comprehensive state health reform initiatives.

Policy makers, consumers, providers and purchasers of health care will do well to pay close attention to the many comprehensive health care reform initiatives under consideration by state legislatures.

Innovation, public choice and public control in the market for health insurance.

Innovation, public choice and public control in the market for health insurance/benefits in the United States are largely dependent upon the ability of the various stakeholders to successfully argue their positions with legislators, regulators, providers, purchasers and third party beneficiaries. Given the public/private nature of health benefits, these relationships are examined in a Stigler/Posner/Peltzman public choice framework. Conflicts among various stakeholders and their ability to influence innovation in the market for health benefits are discussed.

Collectively bargained public health benefit plans.

The marketplace for health benefits for public sector employees is large and complex with a great variety of approaches for providing care and a difficult patchwork of regulatory and collective bargaining regulation to deal with in designing a plan. Public sector workers' plans are subject to an additional constraint provided by the political nature of the process. The products sold to public sector plans are not regulated as ERISA plans, given the exclusion of government plans and the differential regulation of collectively bargained plans under the HMO act. This article attempts to guide the reader through some of the difficulties of this marketplace, pointing out pitfalls and opportunities where they appear.

Challenges and opportunities in the provision of long-term care.

The demands for long-term care are substantial and, given our nation's demographics, are likely to become a critical issue for the economy. Through employee assistance programs and the provision of long-term care benefits, employers are likely to see a substantial increase in individuals' concern for the provision of care.

Single payer: the California referendum.

The California Health Security Act is likely to appear on the November 1994 ballot. The bill would provide universal coverage to California residents and assign the state as the single payer for all medical care provided, financed with funding for programs already in place, employer payroll taxes, individual income taxes and taxes on tobacco products.

Health care challenges and opportunities in the 1990s.

The 1990s offer both substantial challenges and opportunities for those involved in the delivery of health care. Increasing costs must be managed to ensure that the health of both Americans and America's economy are maintained. Managed care offers the brightest hope for effectively controlling costs while increasing the quality of care.

Cognitive outcomes after deep brain stimulation for Parkinson's disease: a review of initial studies and recommendations for future research.

Modern ablative surgery for movement disorders probably results in less frequent and severe cognitive morbidity than seen in early surgical series. Nonetheless, recent studies indicate that neurobehavioral functions commonly compromised in Parkinson's disease (PD) (e.g., executive functions, verbal fluency, and memory) are negatively impacted in some patients by lesion placement. The potential reversibility of cognitive dysfunction after chronic electrical deep brain stimulation (DBS) for PD has lead some to favor this treatment modality over ablation. This paper reviews the initial studies of the cognitive effects of thalamic, pallidal, and subthalamic DBS. These studies suggest that DBS is relatively safe from a cognitive standpoint and that the benefits of motor improvements probably outweigh the cost of minimal cognitive morbidity. This conclusion must be offered with caution, however, given the small numbers of studies to date and their methodological limitations. Neurobehavioral research has yet to adequately address (1) outcome relative to appropriate control groups; (2) effects of electrode placement versus stimulation; (3) laterality- and site-specific effects of DBS; (4) long-term effects of DBS; (5) effects of stimulation parameters; (6) risk factors for cognitive dysfunction with DBS; (7) whether cognitive dysfunction associated with DBS is reversible; and (8) comparative neurobehavioral outcome after DBS and ablation. DBS affords an exciting opportunity to clarify the neurobehavioral role of the basal ganglia.