Showing papers in "Neurology in 1994"

The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia

Abstract: We developed a new instrument, the Neuropsychiatric Inventory (NPI), to assess 10 behavioral disturbances occurring in dementia patients: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, and aberrant motor activity. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patient's behavior. Studies reported here demonstrate the content and concurrent validity as well as between-rater, test-retest, and internal consistency reliability; the instrument is both valid and reliable. The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part V. A normative study of the neuropsychological battery

Abstract: The neuropsychological tests developed for the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) are currently used to measure cognitive impairments of Alzheimer's disease (AD) in clinical investigations of this disorder. This report presents the normative information for the CERAD battery, obtained in a large sample (n = 413) of control subjects (ages 50 to 89) who were enrolled in 23 university medical centers in the United States participating in the CERAD study from 1987 to 1992. We compared separately the performance of subjects with high (> or = 12) and low (< 12) years of formal education. For many of the individual cognitive measures in the highly educated group, we observed significant age and gender effects. Only the praxis measure showed a significant age effect in the low-education group. Delayed recall, when adjusted for amount of material acquired (savings), was relatively unaffected by age, gender, and level of education. Our findings suggest that the savings scores, in particular, may be useful in distinguishing between AD and normal aging.

Cerebral white matter lesions, vascular risk factors, and cognitive function in a population‐based study The Rotterdam Study

Abstract: Cerebral white matter lesions are a common finding on MRI in elderly persons. We studied the prevalence of white matter lesions and their relation with classic cardiovascular risk factors, thrombogenic factors, and cognitive function in an age- and gender-stratified random sample from the general population that consisted of 111 subjects 65 to 84 years of age. Overall, 27% of subjects had white matter lesions. The prevalence and severity of lesions increased with age. A history of stroke or myocardial infarction, factor VIIc activity, and fibrinogen level were each significantly and independently associated with the presence of white matter lesions. Significant relations with blood pressure level, hypertension, and plasma cholesterol were present only for subjects aged 65 to 74 years. White matter lesions tended to be associated with lower scores on tests of cognitive function and were significantly associated with subjective mental decline. This study suggests that classic cardiovascular risk factors, as well as thrombogenic factors, are associated with white matter lesions in subjects over 65 years of age in the general population, and that these lesions may be related to cognitive function.

Preliminary NINDS neuropathologic criteria for Steele‐Richardson‐Olszewski syndrome (progressive supranuclear palsy)

Abstract: We present the preliminary neuropathologic criteria for progressive supranuclear palsy (PSP) as proposed at a workshop held at the National Institutes of Health, Bethesda, MD, April 24 and 25, 1993. The criteria distinguish typical, atypical, and combined PSP. A semiquantitative distribution of neurofibrillary tangles is the basis for the diagnosis of PSP. A high density of neurofibrillary tangles and neuropil threads in the basal ganglia and brain-stem is crucial for the diagnosis of typical PSP. Tau-positive astrocytes or their processes in areas of involvement help to confirm the diagnosis. Atypical cases of PSP are variants in which the severity or distribution of abnormalities deviates from the typical pattern. Criteria excluding the diagnosis of typical and atypical PSP are large or numerous infarcts, marked diffuse or focal atrophy, Lewy bodies, changes diagnostic of Alzheimer's disease, oligodendroglial argyrophilic inclusions, Pick bodies, diffuse spongiosis, and prion protein-positive amyloid plaques. The diagnosis of combined PSP is proposed when other neurologic disorders exist concomitantly with PSP.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part VI. Family history assessment: A multicenter study of first-degree relatives of Alzheimer's disease probands and nondemented spouse controls

Abstract: Although familial factors in Alzheimer9s disease (AD) are well established, uniform family-history assessment in genetic and epidemiologic studies of AD is needed to reconcile the divergent estimates of the cumulative risk of this illness among relatives of AD probands. To answer the need, the Consortium to Establish a Registry for Alzheimer9s Disease (CERAD) has developed a standardized Family History Assessment of AD to identify the presence of AD, Parkinson9s disease (PD), and Down9s syndrome (DS) in family members. This paper describes the use of this new assessment instrument in 118 patients with AD (estimated mean age at onset [± SD] = 64.5 ± 7.7 years) and their nondemented spouses who were enrolled in 11 different CERAD sites in the U.S. The first-degree relatives of the probands with AD had a significantly greater cumulative risk (p

Inverse association of anti‐inflammatory treatments and Alzheimer's disease: Initial results of a co‐twin control study

Abstract: We conducted a co-twin control study among 50 elderly twin pairs with onsets of Alzheimer's disease (AD) separated by 3 or more years. Twenty-three male pairs (46%) were screened from the (U.S.) National Academy of Sciences-National Research Council Registry (NAS-NRC Registry) of World War II veteran twins; others (mostly women) had responded to advertisements or were referred from AD clinics. Twenty-six pairs (52%) were monozygous. The onset of AD was inversely associated with prior use of corticosteroids or ACTH (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.06 to 0.95; p = 0.04). Similar but weaker trends were present among pairs discordant for history of arthritis or for prior daily use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. The association was strongest when we combined use of steroids/ACTH or NSAIDs post hoc into a single variable of anti-inflammatory drugs (AIs) (OR, 0.24; CI, 0.07 to 0.74; p = 0.01). The inverse relation was strong in female (volunteer) twin pairs but was not present in the younger men from the NAS-NRC Registry. AIs had typically been taken for arthritis or related conditions, but a similar result was apparent after controlling statistically for the arthritis variable (OR, 0.08; CI, 0.01 to 0.69; p = 0.02). AIs have been proposed as a means of retarding the progression of AD symptoms, and these data suggest that AIs may also prevent or delay the initial onset of AD symptoms. Because of limitations in the case-control method, our results require corroboration with hypothesis-driven research designed to control bias and confounding.

The role of glutamate in epilepsy and other CNS disorders.

Abstract: Glutamate is the principal excitatory neurotransmitter in the brain and, as such, it inevitably plays a role in the initiation and spread of seizure activity. It also plays a critical role in epileptogenesis. The process of "kindling" limbic seizures in rodents by repeated electrical stimulation is dependent on activation of N-methyl-D-aspartate (NMDA) receptors. The function of these receptors is enhanced in the hippocampus of kindled rats and in the cerebral cortex of patients with focal epilepsy. Microdialysis studies show an increase in the extracellular concentration of glutamate and aspartate before or during seizure onset, suggesting that either enhanced amino acid release or impaired uptake contributes to seizure initiation. Glutamate antagonists selective for NMDA or non-NMDA receptors are potent anticonvulsants when given systemically in a wide variety of animal models of epilepsy. They are of limited efficacy against kindled seizures in rats and (on the basis of preliminary evidence) in patients with drug-refractory complex partial seizures. Cognitive side effects appear to be a significant problem with competitive, as well as noncompetitive, NMDA antagonists. Glutamate receptor antagonists provide significant protection against brain damage following global or focal cerebral ischemia or acute traumatic injury in rodent models. Anticonvulsant compounds of the lamotrigine type, which act on sodium channels and reduce ischemia-induced glutamate release, are cerebroprotective in rodent ischemia models and are free from the cognitive side effects of NMDA-receptor antagonists.

Predictors of mortality and recurrence after hospitalized cerebral infarction in an urban community The Northern Manhattan Stroke Study

Abstract: Objective: To identify determinants of recurrence and mortality after ischemic stroke in a mixed-ethnic region. Background: The determinants of ischemic stroke outcome are not uniformly characterized and will be of increasing importance as the frequency of ischemic stroke survivors increases in our aging population. Methods: A cohort of 323 patients (40% black, 34% Hispanic, 26% white) with cerebral infarction from northern Manhattan over age 39 were followed for a mean of 3.3 years, with only 6% lost to follow-up. Cumulative life table risk of mortality and recurrence was calculated. Risk factors classified at the time of index ischemic stroke were selected based on univariate analyses and then entered into a Cox proportional hazards model for mortality and for recurrence. Results: The life table cumulative risk of mortality was 8% at 30 days, 22% at 1 year, and 45% at 5 years after ischemic stroke. The immediate cause of death was related to vascular disease in 60%. After age adjustment, the significant predictors of mortality were congestive heart failure (risk ratio [RR] = 2.6), admission glucose >140 mg/dl (RR = 1.7), and presentation with either a large dominant, nondominant, or major basilar syndrome (RR = 2.0). Patients with a lacunar syndrome had a better survival (RR = 0.6). Recurrent strokes occurred in 72 patients. The life table cumulative risk of recurrence was 6% at 30 days, 12% at 1 year, and 25% at 5 years after ischemic stroke. Ethanol abuse (RR = 2.5), hypertension requiring discharge medications (RR = 1.6), and elevated blood glucose within 48 hours of index ischemic stroke (RR = 1.2 per 50 mg/dl) were the independent predictors of recurrence. Among 30-day survivors, the effect of ethanol abuse was greater (RR = 3.5), indicating its impact on late recurrence. Conclusions: After accounting for age and presenting syndrome, initial glucose predicts stroke mortality and recurrence after ischemic stroke. This association may reflect uncontrolled and undiagnosed diabetes in our urban population. Furthermore, ethanol abuse may be a determinant of ischemic stroke recurrence. Reduction of the stroke public health burden will require targeted modification of such conditions and behaviors.

Manganism and idiopathic parkinsonism : Similarities and differences

Abstract: From the comparison we have made between PD and manganism, we draw the following conclusions: 1. There are similarities between PD and manganism, notably the presence of (a) generalized bradykinesia and (b) widespread rigidity. 2. There are also dissimilarities between PD and manganism, notably the following in manganism: (a) less-frequent resting tremor, (b) more frequent dystonia, (c) a particular propensity to fall backward, (d) failure to achieve a sustained therapeutic response to levodopa, and (e) failure to detect a reduction in fluorodopa uptake by PET. Further studies are likely to yield more discriminants between PD and manganism. For example, PET with raclopride may be useful in early cases of manganism, and MRI may be helpful in patients with advanced manganism.

Electron transport chain defects in Alzheimer's disease brain

Abstract: Previous work suggested a deficiency in the terminal complex of the mitochondrial electron transport chain, cytochrome c oxidase (COX), in platelet mitochondria of Alzheimer's disease (AD) patients. The present study extends this observation to AD brain mitochondria through assay of electron transport chain activities in mitochondria isolated from autopsied brain samples from AD patients (n = 9) and from controls with and without known neurologic disease (n = 8). AD brain mitochondria demonstrated a generalized depression of activity of all electron transport chain complexes. This depression was most marked in COX activity (p < 0.001). Concentrations of cytochromes b, c1, and aa3 were similar in AD and controls. The electron transport chain is defective in AD brain, and the defect centers about COX.

Neuropsychological prediction of dementia and the absence of dementia in healthy elderly persons.

Abstract: Identification of elderly individuals with low and high risk for future dementia has emerged as an important clinical and public health issue. To address this issue, we assessed neuropsychological performance in 317 initially nondemented elderly persons between 75 and 85 years of age and followed them for at least 4 years as part of the Bronx Aging Study. Four measures of cognitive function from the baseline assessment (delayed recall from the Buschke Selective Reminding Test, recall from the Fuld Object Memory Evaluation, the Digit Symbol subtest from the Wechsler Adult Intelligence Scale, and a verbal fluency score) can identify one subgroup with an 85% probability of developing dementia over 4 years and another with a 95% probability of remaining free of dementia. The model achieved an overall positive predictive value of 68%, or three times the base rate, for prediction of the development of dementia in our sample. The overall negative predictive value for prediction of absence of dementia was 88%. Baseline measures of cognitive function, often performed many years before the actual diagnosis of dementia, can provide important information about dementia risk. The group likely to develop dementia becomes a target for preventive or early therapeutic interventions, and the group unlikely to develop dementia can be reassured.

Migraine prevalence. A review of population-based studies

Abstract: Obtaining accurate and reliable information on the prevalence of migraine is essential to understanding the burden it places on society. Although the epidemiology of headache has been described in more than 50 population-based studies, only 24 of these have described the gender- and age-specific prevalence of migraine. Essentially five different case definitions have been used in these studies. Variation in the prevalence of migraine among studies is largely due to differences in case definition and in the age and gender distribution of study populations. Among four recent studies that used the diagnostic criteria of the International Headache Society (IHS), a coherent picture emerges. The prevalence of migraine is approximately 6% among men and 15 to 17% among women. Prevalence varies by age, increasing to about age 40 years and declining thereafter in both men and women. The gender ratio also appears to vary by age, increasing from menarche to about age 42 years and declining thereafter. Although the use of the IHS criteria has resulted in a more coherent picture across population-based studies, efforts must be made to assess the reliability and validity of these criteria in population-based samples.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder

Abstract: We studied the clinical, biochemical, and genetic features of eight patients with the autosomal recessive mitochondrial syndrome mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is clinically characterized by ophthalmoparesis, peripheral neuropathy, leukoencephalopathy, gastrointestinal symptoms (recurrent nausea, vomiting, or diarrhea) with intestinal dysmotility, and histologically abnormal mitochondria in muscle. Brain MRI scans were consistent with leukodystrophy in seven patients examined. Nerve conduction and EMG studies were compatible with a sensorimotor neuropathy; quantitative EMG of two patients suggested a myogenic process. Muscle mitochondrial enzyme analysis revealed a partial defect of cytochrome c oxidase activity in five patients; three had additional respiratory chain enzyme defects. Two patients had isolated complex I defects, and one had normal respiratory chain function. Southern blot analysis revealed multiple deletions of mitochondrial DNA in four of eight patients.

The limit of tactile spatial resolution in humans Grating orientation discrimination at the lip, tongue, and finger

Abstract: The sensory neural pathways serving the lip, tongue, and finger are specialized for spatial information processing; thus, damage to these pathways is likely to be manifested most prominently as a loss of spatial acuity. For that reason, accurate measurement of spatial resolution at these regions is particularly important. The conventional test, the two-point discrimination task, does not measure the limit of spatial resolution and it yields variable results because it does not control nonspatial cues. The aim of this study was to quantify the limits of spatial resolution at the lip, tongue, and finger and to study the repeatability of those measurements using a stimulus that does not introduce nonspatial cues. We employed a grating orientation discrimination test, which has been studied extensively in relation to the underlying neural mechanisms. We obtained psychophysical thresholds for tactile spatial resolution from 15 normal, young adult subjects over seven test sessions. The finest gratings whose orientations were discriminated reliably had groove widths (gratings had equal groove and bar widths) that averaged 0.51 mm at the lip, 0.58 mm at the tongue, and 0.94 mm at the finger. These threshold measurements were highly reproducible between sessions with an overall improvement of 2% per session. These data suggest that the grating orientation discrimination task provides a stable, reliable measure of the human capacity for spatial resolution.

HIV‐1 infection of subcortical astrocytes in the pediatric central nervous system

Abstract: Early reports of pediatric HIV-1-associated neuropathology described the presence of viral particles in some astrocytes, implicating direct infection of the immature nervous system as a contributing factor to the observed neuropathology. Several recent reports suggest that in those astrocytes infected with HIV-1, the level of antigenic expression of the proviral genome is below the sensitivity limits of conventional histochemical techniques. Identification of these astrocytes would instead require the use of a highly sensitive radiolabeled DNA or RNA probe for in situ hybridization to detect the persistent viral nucleic acids. To test this hypothesis, we examined autopsy tissue from 12 infants and children with AIDS-associated encephalopathy for the presence of HIV-1-infected astrocytes using combined isotopic in situ hybridization for the detection of viral-specific nucleic acids and immunohistochemistry for the identification of astrocytes. We detected HIV-1 nucleic acids in astrocytes in subcortical white matter from four pediatric patients with moderate to extensive leukoencephalitis. While gp41 was detectable only on macrophages and multinucleated giant cells, HIV-1 Nef protein was present in cells morphologically identified as astrocytes in two of these patients, further suggesting that HIV-1 establishes a persistent rather than a productive infection in astrocytes. Subcortical astrocytes may therefore be an unrecognized reservoir for HIV-1 in the developing nervous system of some children with AIDS-associated leukoencephalitis.

Surgical Treatment of the Epilepsies, 2nd Ed.

Abstract: ic (speech sound) encoding of the word in the context of an utterance. The first four chapters of the book investigate the ability to transform a message we are thinking to the word-forms required for i t s expression. Taken together, th i s section describes the process of moving from a concept to the selection of a lexical item, and provides a computer model for lemma retrieval that involves mental activation spreading from a triggered concept to the word-form stage. It appears that lemma retrieval obeys both semantic (meaning) and grammatical (structural) constraints available from the word‘s context, and that failures in lexical selection in pathologic states may be related to semantic or grammatical category effects. The next three chapters of the book are concerned with the phonetic realization of a word-form. Words themselves have a characteristic structure, and it appears that the structure of a word plays an important role in eliciting a speech error. Methodologic issues have restricted the nature of speech error analyses in normal subjects, and a critical examination of the aphasic speech error literature has additionally revealed that few investigators have examined error consistency in individual aphasics. Inconsistent speech error patterns in aphasia are unlikely to be due to the actual loss of phonologic information, but instead to the compromised transmission of information between processing subsystems. This book will be of most immediate interest to aphasiologists, but its significance for a much larger audience should not be lost. The contributors illustrate important new approaches to the assessment of human cognition in individuals with CNS disease. It is through the efforts of researchers such as these that nonspecific behavioral descriptors such as ”word-finding difficulty” will soon be replaced by more meaningful characterizations that are theoretically motivated and therapeutically significant.

Anti‐ICAM‐1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat

Abstract: Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein expressed on endothelial cells that facilitates leukocyte adhesion. To test the hypothesis that reduction of leukocytes in an ischemic lesion reduces ischemic brain damage, we measured the effect of administration of an anti-ICAM-1 monoclonal antibody on ischemic brain damage after transient middle cerebral artery occlusion in the rat. ICAM-1 expression increased in the ischemic lesion, and the lesion volume was significantly reduced by 41% in the anti-ICAM-1 antibody group compared with the control group (p < 0.05). Numbers of polymorphonuclear leukocytes (PMNs) were significantly reduced in the cortices of the anti-ICAM-1 antibody group compared with the control animals (p < 0.05). Our data indicate that administration of anti-ICAM-1 antibody results in a significant reduction of ischemic brain damage concomitant with a reduction of PMNs in the lesion after transient focal cerebral ischemia in the rat.

Overexpression of nef as a marker for restricted HIV‐1 infection of astrocytes in postmortem pediatric central nervous tissues

Abstract: In previous studies, using polymerase chain reaction amplification of HIV-1 genes directly from pathologic tissues of children who died with AIDS encephalopathy, we showed that the reading frame of the HIV-1 regulatory nef gene is open, suggesting that the nef protein was expressed. We now show, using immunocytoehemistry and in situ hybridization with nef -specific probes in postmortem pediatric CNS tissues, that nef mRNA and protein are present in up to 20% of astrocytes in tissue sections selected for extensive histopathology. By contrast, HIV-1 structural proteins such as gag and their coding mRNAs are present in multinucleated giant cells that harbor productive infection and are the hallmark of HIV-1 infection in the CNS. These findings are consistent with the nonproductive infection of glial cells observed in vitro, and imply that HIV-1 infection of astrocytes is restricted to early regulatory gene products, of which nef is the best target as it is expressed at high levels and is membrane-anchored. In developing central nervous tissues of children, restricted and latent HIV-1 infection of astrocytes may be extensive and contribute significantly to HIV-1 neuropathogenesis.

Precursors of extracranial carotid atherosclerosis in the Framingham Study.

Abstract: To investigate cardiovascular risk factors and carotid atherosclerosis, we related previously measured risk factors to carotid atherosclerosis as determined by duplex ultrasonography in the Framingham Study cohort. Risk factors measured prospectively on 1,116 cohort members, ages 66 to 93, were related to the severity of carotid atherosclerosis measured by carotid ultrasonography performed during biennial examination no. 20 (1988 to 1990). The degree of carotid atherosclerosis was expressed as a percent carotid stenosis and, for statistical analysis, subjects were divided into four groups according to percent carotid stenosis. The prevalence of significant carotid stenosis in the general population was low--7% in women and 9% in men. A multivariate logistic regression model showed that age, cigarette smoking, systolic blood pressure, and cholesterol were independently related to carotid atherosclerosis. Alcohol consumption was also significant in men, but not in women. In addition, our results indicate that both current and former smoking in both sexes was related to the degree of carotid atherosclerosis.

Memory function in very early Alzheimer's disease

Abstract: The detection of very early Alzheimer's disease (AD) can be important for both theoretical and practical reasons. Typically, a memory impairment is the first sign of incipient disease, but the early clinical diagnosis can be challenging. We investigated several aspects of memory function in AD and normal aging to determine which indices of performance were most sensitive at detecting early impairments. We evaluated 106 pairs of patients with probable AD and matched controls from the Mayo Clinic Alzheimer's Disease Patient Registry using a logistic regression model that included measures of memory function, verbal and nonverbal intelligence, attention, and language. Results indicated that an index of learning, especially with semantic cuing, was most sensitive at separating the two groups. We then matched subsets of individuals from the larger groups of AD and control subjects on the Mini-Mental State Examination (range of scores, 24 to 26). A logistic regression analysis on these matched groups yielded the same results. A measure of learning with facilitation of performance using cues appears to be the best discriminator at detecting very mild AD. These measures can be useful in selecting patients for interventional strategies.

The British Isles survey of multiple sclerosis in twins

Abstract: During a 27-month recruitment period, we identified 146 individuals with multiple sclerosis (MS) who have a twin. A single clinician interviewed and examined 105 pairs of twins, and we confirmed zygosity using minisatellite probes. Including two suspected cases, 11 of 44 (25%) monozygotic twin pairs were concordant compared with two of 61 (3%) dizygotic twin pairs–two of 33 (6%) like-sexed and zero of 28 (0%) opposite-sexed. MRI was performed in 64 of 105 co-twins, and showed abnormalities consistent with demyelination in 13% of monozygotic and 9% of dizygotic co-twins who were clinically unaffected. These findings are similar to the results of most previous studies of MS in twins in which zygosity was not unequivocally established and where the majority of clinically unaffected co-twins were not studied by MRI; the difference in concordance rates in monozygotic and dizygotic twins indicates a significant genetic component in the etiology of MS.

The cerebellum contributes to linguistic production: A case of agrammatic speech following a right cerebellar lesion

Abstract: We describe a patient who, after a right cerebellar infarction, developed a right hemicerebellar syndrome and agrammatic speech without other cognitive impairments. We hypothesize that the cerebellum provides the temporal interplay among the neural structures underlying the processes responsible for production of sentences.

Magnetic resonance spectroscopy in temporal lobe epilepsy

Abstract: We used proton magnetic resonance spectroscopy (1H MRS) to investigate the temporal lobes of 25 patients with temporal lobe epilepsy. Spectra were obtained from 2 x 2 x 2 cm cubes in the medial region of the temporal lobe, and were analyzed on the basis of signals from N-acetylaspartate (NAA), creatine + phosphocreatine (Cr), and choline-containing compounds (Cho). In comparison with control subjects, the temporal lobes ipsilateral to the seizure focus showed a mean reduction of 22% in the NAA signal, with a 15% increase in the Cr signal and a 25% increase in the Cho signal. There were smaller effects in the contralateral temporal lobes. These spectral abnormalities may reflect neuronal loss or damage, together with reactive astrocytosis. The NAA/Cho+Cr ratio was abnormally low in 88% of the patients, 40% showing bilateral effects. On the basis of the NAA/Cho+Cr ratio, we correctly achieved lateralization in 15 cases, with three incorrect. Two of the incorrect lateralizations also had imaging abnormalities on the contralateral side, and the other had severe bilateral abnormalities on MRS. We conclude that 1H MRS provides useful information in the preoperative investigation of patients with temporal lobe epilepsy, contributing to lateralization and detecting bilateral abnormalities.

Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis

Abstract: We performed semiautomated quantitative measurement of brain magnetic resonance imaging (MRI) abnormalities seen at presentation and at 5-year follow-up in 84 patients presenting with an acute clinically isolated syndrome of the optic nerves, brainstem, or spinal cord suggestive of multiple sclerosis (MS). At follow-up, 34 (40%) had developed clinically definite and four (5%) clinically probable MS. Patients who developed MS during follow-up had a higher lesion load at presentation than those who did not. There was a strong correlation of the MRI lesion load at presentation with both the increase in lesion load over the next 5 years and disability at follow-up. Increasing initial lesion load correlated with a decreasing time to development of MS clinically (r = −0.328, p

High prevalence of vitamin D deficiency and reduced bone mass in multiple sclerosis

Abstract: Background: Female patients with multiple sclerosis (MS) are at risk for osteoporosis because of gender, immobility, and corticosteroid use. Methods: Bone mineral density (BMD) was measured by dual x-ray absorptiometry in 80 female MS patients admitted to a tertiary care hospital. All patients completed a questionnaire that included measurements of dietary intake and sunlight exposure. Biochemical indices of bone metabolism and turnover were measured in a random sample of 52 patients. Results: BMD of the lumbar spine and femoral neck was 1 to 2 SDs lower in MS women compared with a healthy reference population. BMD was lower in patients with more severe MS. The mean 25(OH)D level of the sample population (43 nmol/1) was in the insufficient range, and 12 patients (23%) had frank vitamin D deficiency ( Conclusions: BMD was significantly reduced in female MS patients, which might increase fracture risk two- to threefold. Vitamin D deficiency with secondary hyperparathyroidism is prevalent and is probably a significant cause of low BMD in this population. Vitamin D deficiency in the female MS patient might be safely and inexpensively corrected by the routine use of vitamin D supplements.

Temporal trends in the incidence of HIV-1-related neurologic diseases: Multicenter AIDS Cohort Study, 1985-1992.

Abstract: Objective: To describe temporal trends in the incidence of human immunodeficiency virus (HIV)-re-lated neurologic diseases in the Multicenter AIDS Cohort Study from 1985 to 1992. Methods: The incidence rates of six neurologic disorders were examined: toxoplasmosis, cryptococcal meningitis, primary CNS lymphoma, progressive multifocal leukoencephalopathy, HIV dementia, and sensory neuropathy. Poisson modeling was used to test linear trends over time and the effects of progressive immunosuppression, antimicrobial prophylaxis, and antiretroviral drug therapy. Results: There was an upward temporal trend in all incidence rates, except for HIV dementia. Progressive immunosuppression in the cohort explained all calendar trends except for sensory neuropathy, where an increasing temporal trend remained even after adjusting for CD4 + cell count, and for HIV dementia where a slight decline was noted, although the effects were not statistically significant. We noted a protective trend of antimicrobial prophylaxis on toxoplasmosis and cryptococcal meningitis, but, in contrast, use of antiretroviral agents was not protective against HIV dementia. Men receiving didanosine, zalcitabine, or stavudine were more likely to develop sensory neuropathy. Conclusion: Despite the earlier and more widespread use of antimicrobial and antiretroviral agents, neurologic conditions still occurred frequently in this cohort, with annual rates above 1.5 per 100 person-years for HIV dementia and sensory neuropathy. Sensory neuropathy seems to be increasing in incidence and HIV dementia declining slightly in this cohort. As the epidemic matures and more people with profound immunosuppression live longer, the overall incidence of HIV-related neurologic diseases can be expected to rise.

Spasticity: a review.

Abstract: This symposium is concerned with the treatment of spasticity and, in particular, with results from studies of tizanidine as a treatment for patients with MS and spinal cord injury. In this article, the definitions and pathophysiologies of spasticity are reviewed, and the issue of when and if to treat spasticity is evaluated. The merits of newer pharmacologic and invasive therapies are discussed relative to reduction of patient discomfort and the possibility of restored function.

Comorbidity of migraine and epilepsy

Abstract: We investigated comorbidity of migraine and epilepsy by using information from structured telephone interviews with 1,948 adult probands with epilepsy and 1,411 of their parents and siblings. Epilepsy was defined as a lifetime history of two or more unprovoked seizures, and migraine as severe headaches with two or more of the following symptoms: unilateral pain, throbbing pain, visual aura, or nausea. Cumulative incidence of migraine to age 40 was 24% in probands with epilepsy, 23% in relatives with epilepsy, and 12% in relatives without epilepsy. Using Cox proportional hazards analysis to control for years at risk and gender, the rate ratio for migraine was 2.4 (95% CI, 2.02 to 2.89) among probands and 2.4 (1.58 to 3.79) among relatives with epilepsy in comparison with relatives without epilepsy. Migraine risk was highest in probands with epilepsy due to head trauma, but it was significantly higher in every subgroup of probands than in unaffected relatives when probands were stratified by seizure type, age at onset, etiology of epilepsy, and history of epilepsy in first-degree relatives. Age-specific incidence of migraine among probands was increased to a greater extent after onset of epilepsy than before, but it was also significantly increased more than 5 years before onset and 1 to 5 years before onset. These results indicate that migraine and epilepsy are strongly associated, independent of seizure type, etiology, age at onset, or family history of epilepsy.

Risk of dementia after stroke in a hospitalized cohort: results of a longitudinal study

Abstract: Stroke is considered the second most common cause of dementia, but the magnitude of the risk posed by stroke has not been fully clarified. The aim of this study was to determine the long-term risk of developing dementia after stroke onset in a hospitalized cohort. We prospectively examined 185 nondemented patients aged > or = 60 years hospitalized with ischemic stroke and 241 age-matched nondemented controls without stroke from the same community using neurologic, neuropsychological, and functional assessments given annually. Using criteria modified from the DSM-III-R, we diagnosed incident dementia based on the annual examination findings. We used life-table methods to estimate incidence in the two groups, Kaplan-Meier analysis to determine the proportion surviving without dementia, and Cox proportional-hazards analysis to compute the relative risk (RR) of dementia after 1 to 4 years of follow-up. The incidence of dementia was 8.4 per 100 person-years in the stroke group and 1.3 per 100 person-years in the control group. After 52 months of follow-up, the cumulative proportion (+/- SE) surviving without dementia was 66.3 +/- 5.5% for stroke and 90.3 +/- 4.3% for control subjects. The RR of dementia associated with stroke compared with controls was 5.5 (95% CI, 2.5 to 11.1) after adjusting for demographic factors. Older age at stroke onset and fewer years of education were significant covariates, but sex and race were not. A low score on the Mini-Mental State Examination at baseline was a significant predictor when added to this model.(ABSTRACT TRUNCATED AT 250 WORDS)