Douglas J. Lanska

Progressive Multifocal Leukoencephalopathy in Patients with HIV Infection

Progressive multifocal leukoencephalopathy (PML), a formerly rare disease, is estimated to occur in up to 5% of all patients with AIDS. The high prevalence of PML in AIDS patients currently enables a comprehensive evaluation of this disorder. We evaluated the clinical and radiographic features of PML in a large cohort of AIDS patients identified by retrospective chart review from 1981 to 1994. Two hundred and five patients were diagnosed with PML of which 154 met the inclusion criteria. Seventy-two (47%) were pathologically confirmed and the remaining 82 (53%) met clinical and radiographic criteria. There was a 12-fold increase in the frequency of PML between 1981-1984 and 1991-1994. PML affected 136 men and 18 women with AIDS. Eighty-four percent of cases were 20-50 years old (range 5 to 68 years). The most common AIDS risk factors were homosexuality (57%) among men and heterosexual transmission (28%) and intravenous drug abuse (28%) among women. In 27% of patients, PML heralded AIDS. Common manifestations included weakness, gait abnormalities, speech disturbance, cognitive disorders, headache, and visual impairment. The CD4 lymphocyte counts exceeded 200 cells in 11% at the time of presentation. Involvement of posterior fossa structures was evident in 48% of cranial magnetic resonance imaging (MRI) studies, but in only 11% of computed tomographies (CT) of the brain. Contrast enhancement, typically faint and peripheral, was seen in 10% of CT scans and 15% of MRIs. The median survival was 6 months and survival exceeded 1 year in 9%. PML is no longer a rare disease. It often heralds AIDS and may occur in the absence of significant decline in CD4 lymphocytes. Survival is generally poor, although prolonged survival beyond 1 year is not unusual.

Diagnosis and evaluation of dementia

This document will outline what we believe to be the most useful components of the diagnostic evaluation of elderly patients with cognitive complaints. It will focus on identifying and diagnosing the two major dementing disorders, Alzheimer’s disease (AD) and vascular dementia (VD). AD, the most common cause of cognitive decline in the elderly, has an estimated prevalence of 3 to 11% in communitydwelling persons over age ~ixty-five.l-~ This age group is increasing, and therefore the number of patients with dementia and AD will increase. It is estimated that there will be at least 7 million AD patients in the United States by the early 21st cent ~ r y . ~ , ~ The financial consequences will be staggering, as costs may approach 50 to 100 billion dollars per year.6 In view of increasing life expectancy, AD and its complications may rank as the fourth or fifth most common cause of death in the United state^.^ Accurate diagnosis of dementia syndromes is important to detect reversible or arrestable dementias. In addition, the impact of dementia on a patient’s family is substantial, and accurate diagnosis enables the clinician to provide the patient and family with a more reliable prediction of the disease course. This will facilitate planning to provide the necessary social resources. Finally, standardization of the diagnostic approach to dementia and AD is important in clinical research, including epidemiologic surveys and therapeutic trials. The impact on health care costs of diagnostic evaluations for dementia, like all medical practices, has recently come under much scrutiny. Some question the expense of the assessment, citing the economic burden of “routine work-ups” in this era of fiscal responsibility. Although the estimated cost of the average dementia evaluation (

Presentation, clinical course, and outcome of childhood stroke

1,000 to

The Geography of Stroke Mortality in the United States and the Concept of a Stroke Belt

1,200) may seem high, we believe it is highly cost-effective when compared with the average expenditure for institutionalization (

Peripartum stroke and intracranial venous thrombosis in the National Hospital discharge survey

25,000 to

Familial progressive subcortical gliosis.

35,000 per year for several years) when a case of reversible dementia is missed. Background. The DSM-III-R (1987P defines the term “dementia” as a syndrome (produced by many disorders) characterized by impairment from a previously higher level of intellectual functioning. The impairment involves memory and other cognitive domains, including language, orientation, constructional abilities, abstract thinking, problem solving, and praxis, and must be of sufficient severity to interfere with occupational or social performance or both, ie, functional impairment. Changes in personality and affect are often noted, but a normal level of consciousness is preserved until the very late stages of the disorder. Patients with cognitive impairment without evidence of a functional decline do not strictly meet DSM-III-R criteria for dementia. These patients are often classified in a variety of ways, such as having “benign senescent forgetfulness” or “age-associated memory impairment,” or being “at risk” for dementia. Upon follow-up, however, many of them are found to have a progressive dementia.g Several sets of criteria have been developed for the diagnosis of AD. The two most widely used are those of the DSM-III-R and those formulated by the NINCDS-ADRDA joint task force in 1984.’O The DSM-III-R requires an insidious onset with a generally progressive deteriorating course and exclusion of all other specific causes of dementia. The more detailed NINCDS criteria reserve the designation of “definite” AD for cases with biopsy or autopsy confirmation. Criteria for the diagnosis of “probable” AD, the maximum level of certainty possible without pathologic confirmation, include the insidious onset of decline in memory and at least one other area of cognition, a progressive course, a preserved level of consciousness, and the exclusion of other conditions that could cause these symptoms. Patients with an atypical course, focal neurologic findings, or coexistent disorders that by themselves alone may produce dementia are designated

The geographic distribution of Parkinson's disease mortality in the United States

We reviewed the presentations, clinical courses, and outcomes of 42 children with unilateral hemispheric stroke. Infants with strokes identified within the first few days of life usually presented with seizures. These infants had few abnormal neurologic findings as neonates, but hemiparesis became evident as gross motor development proceeded. Infants with strokes identified later in the first year of life usually presented with pathologic early hand preference without a history of an ictus. During subsequent development, the motor deficits in these children became more evident, producing an apparent progression of the neurologic abnormalities. Strokes identified in older children typically presented as sudden hemiparesis, often associated with seizures. The hemiparesis in these children was most severe at the onset, followed by some improvement in strength in all patients. Functional outcome was variable. At last follow-up, all children were ambulatory, some with clinically apparent hemiparesis. Eight of the 42 children (19%) developed recurrent seizures with an onset ranging from 4 months to more than 10 years (median: 26 months) after the stroke.

Geographic Variation in the Decline of Stroke Mortality in the United States

Since at least 1940 there has been a consistent pattern of marked geographic variation in stroke mortality rates within the United States.1 2 3 Very high rates are reported in the Southeast, and particularly the southeast coastal plain, while very low rates are reported in the Mountain census division and along the northern Atlantic coast.1 2 3 These general patterns of geographic variation have been observed for both sexes and for whites and nonwhites, although stroke rates have been consistently declining in all geographic areas of the continental United States over this interval.1 Comparable age-adjusted and race- and sex-specific data for earlier periods are not available because (1) tabulations of deaths are limited to the Death Registration Area, which did not include all of the coterminous United States until 1933,4 5 6 and (2) US mortality data were first cross-tabulated by age, race, sex, cause of death, and state in 1937. Nevertheless, age-adjusted stroke mortality rates for whites suggest that the current spatial distribution of stroke mortality was not in place in 1920; instead, the high-rate states were apparently concentrated in the northeastern United States.3 From 1920 through 1933, rates declined considerably in all states but particularly in the Northeast, shifting the distribution of excess stroke mortality southward. By 1940, rates had declined further but least in the Southeast, leaving this area with an excess of stroke mortality that has persisted for half a century.nnThe nonrandom distribution of stroke mortality across the United States; the persistence of the pattern over more than five decades; the similarity of the pattern for different age, race, and sex groups; the fact that the pattern is not delimited by county, state, or other political administrative boundaries; and the extreme magnitude of the differences between rates in high- and …

In-hospital mortality following carotid endarterectomy

Objectives: To determine nationally representative estimates of the incidence of peripartum stroke and intracranial venous thrombosis and to identify potential risk factors for these conditions. Methods: We analyzed National Hospital Discharge Survey data for the period 1979–1991. Nationally representative estimates of risk were calculated by age, race, method of delivery, presence of pregnancy-related hypertension, census region, hospital ownership, and number of hospital beds. Multivariate models were developed using logistic and Poisson regression. Results: There were an estimated 5484 cases of peripartum stroke and 4454 cases of intracranial venous thrombosis in the United States among 50,110,949 deliveries (risk, 10.3 cases of peripartum stroke and 8.9 cases of intracranial venous thrombosis per 100,000 deliveries). In both univariate and multivariate models, peripartum stroke was associated strongly with cesarean delivery, pregnancy-related hypertension, proprietary hospital ownership, and larger hospital size. Intracranial venous thrombosis was strongly associated with cesarean delivery and less strongly with smaller hospital size. Conclusions: Peripartum stroke and intracranial venous thrombosis are common complications of pregnancy. Although the associations identified in this study are plausible, further studies are required to confirm these associations and elucidate the underlying mechanisms.

Effects of Interstate Migration on the Geographic Distribution of Stroke Mortality in the United States

We report clinical and pathologic findings from two kindreds afflicted with a familial form of progressive subcortical gliosis. The disorder segregated as an autosomal dominant trait. Onset was in the presenium and the course was slowly progressive. Affected individuals initially manifested personality change, degeneration of social ability, disinhibition, psychotic symptoms, memory impairment, or depression. Later, all developed progressive dementia, frequently associated with verbal stereotypy, decreased speech output, echolalia, or manifestations of the human Klüver-Bucy syndrome. Terminal clinical manifestations included profound dementia, frequently with mutism, dysphagia, and extrapyramidal signs. Autopsy of seven end-stage patients revealed generalized cerebral atrophy, predominantly involving the white matter of the frontal and temporal lobes. Microscopically, prominent fibrillary astrocytosis was present in the subcortical white matter and in the subpial and deep layers of the overlying cerebral cortex. These changes were most pronounced in the frontal and temporal lobes, especially in the cingulate gyri and insulae. Mild cortical neuronal loss accompanied the gliosis, but no myelin loss was evident. The claustra and substantia nigra also showed severe astrocytosis and degenerative changes. Amyloid deposits and neuronal cytoskeletal inclusions were absent.