Richard J. Kryscio

A Randomized Trial of Surgery in the Treatment of Single Metastases to the Brain

To assess the efficacy of surgical resection of brain metastases from extracranial primary cancer, we randomly assigned patients with a single brain metastasis to either surgical removal of the brain tumor followed by radiotherapy (surgical group) or needle biopsy and radiotherapy (radiation group). Forty-eight patients (25 in the surgical group and 23 in the radiation group) formed the study group; 6 other patients (11 percent) were excluded from the study because on biopsy their lesions proved to be either second primary tumors or inflammatory or infectious processes. Recurrence at the site of the original metastasis was less frequent in the surgical group than in the radiation group (5 of 25 [20 percent] vs. 12 of 23 [52 percent]; P less than 0.02). The overall length of survival was significantly longer in the surgical group (median, 40 weeks vs. 15 weeks in the radiation group; P less than 0.01), and the patients treated with surgery remained functionally independent longer (median, 38 weeks vs. 8 weeks in the radiation group; P less than 0.005). We conclude that patients with cancer and a single metastasis to the brain who receive treatment with surgical resection plus radiotherapy live longer, have fewer recurrences of cancer in the brain, and have a better quality of life than similar patients treated with radiotherapy alone.

Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial

BACKGROUND The standard treatment for spinal cord compression caused by metastatic cancer is corticosteroids and radiotherapy. The role of surgery has not been established. We assessed the efficacy of direct decompressive surgery. METHODS In this randomised, multi-institutional, non-blinded trial, we randomly assigned patients with spinal cord compression caused by metastatic cancer to either surgery followed by radiotherapy (n=50) or radiotherapy alone (n=51). Radiotherapy for both treatment groups was given in ten 3 Gy fractions. The primary endpoint was the ability to walk. Secondary endpoints were urinary continence, muscle strength and functional status, the need for corticosteroids and opioid analgesics, and survival time. All analyses were by intention to treat. FINDINGS After an interim analysis the study was stopped because the criterion of a predetermined early stopping rule was met. Thus, 123 patients were assessed for eligibility before the study closed and 101 were randomised. Significantly more patients in the surgery group (42/50, 84%) than in the radiotherapy group (29/51, 57%) were able to walk after treatment (odds ratio 6.2 [95% CI 2.0-19.8] p=0.001). Patients treated with surgery also retained the ability to walk significantly longer than did those with radiotherapy alone (median 122 days vs 13 days, p=0.003). 32 patients entered the study unable to walk; significantly more patients in the surgery group regained the ability to walk than patients in the radiation group (10/16 [62%] vs 3/16 [19%], p=0.01). The need for corticosteroids and opioid analgesics was significantly reduced in the surgical group. INTERPRETATION Direct decompressive surgery plus postoperative radiotherapy is superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer.

Neural substrates of facial emotion processing using fMRI

We identified human brain regions involved in the perception of sad, frightened, happy, angry, and neutral facial expressions using functional magnetic resonance imaging (fMRI). Twenty-one healthy right-handed adult volunteers (11 men, 10 women; aged 18-45; mean age 21.6 years) participated in four separate runs, one for each of the four emotions. Participants viewed blocks of emotionally expressive faces alternating with blocks of neutral faces and scrambled images. In comparison with scrambled images, neutral faces activated the fusiform gyri, the right lateral occipital gyrus, the right superior temporal sulcus, the inferior frontal gyri, and the amygdala/entorhinal cortex. In comparisons of emotional and neutral faces, we found that (1) emotional faces elicit increased activation in a subset of cortical regions involved in neutral face processing and in areas not activated by neutral faces; (2) differences in activation as a function of emotion category were most evident in the frontal lobes; (3) men showed a differential neural response depending upon the emotion expressed but women did not.

Risk Factors for Peripartum and Postpartum Stroke and Intracranial Venous Thrombosis

BACKGROUND AND PURPOSE The study goal was to identify potential risk factors for peripartum or postpartum stroke and intracranial venous thrombosis. METHODS Data from the Healthcare Cost and Utilization Project were analyzed for the years 1993 and 1994. Observed values were weighted with poststratification discharge weights to project to the universe of all discharges from community hospitals located in the United States. Nationally representative estimates of risk were calculated on the basis of age, race, mode of delivery, income, third-party payer, hospital size, hospital ownership, hospital location (rural versus urban), hospital teaching status, census region, and presence of specific complications. Multivariate models were developed with the use of logistic regression. RESULTS Among 1 408 015 sampled deliveries, there were 183 observed cases of peripartum stroke and 170 cases of peripartum intracranial venous thrombosis in 17 states in the United States in 1993 and 1994. There were an estimated 975 cases of stroke and 864 cases of intracranial venous thrombosis during pregnancy and the puerperium in the United States among 7 463 712 deliveries during 1993 and 1994, for estimated risks of 13.1 cases of peripartum stroke and 11.6 cases of peripartum intracranial venous thrombosis per 100 000 deliveries. Multivariate analysis showed that the following were strongly and significantly associated with both peripartum and postpartum stroke: cesarean delivery; fluid, electrolyte, and acid-base disorders; and hypertension. Covariates that were strongly and significantly associated with both peripartum and postpartum intracranial venous thrombosis included cesarean delivery, hypertension, and infections other than pneumonia and influenza. CONCLUSIONS Pregnancy-related hypertension and cesarean delivery are important risk factors for both stroke or intracranial venous thrombosis.

Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease

Mild alterations in cognitive function are present in normal aging and severe cognitive alterations are a hallmark of Alzheimers disease (AD). The cognitive change in AD has been correlated to the characteristic pathologic lesions in the brain, senile plaques (SP) and neurofibrillary tangles. Senile plaques are the most consistent correlative marker in AD. We present preliminary data indicating that abundant SP are found in the brains of nondemented patients dying with or as a result of critical coronary artery disease (cCAD) compared to nonheart disease (non-HD) subjects; 15 of 20 cCAD patients contained SP and only two of 16 non-HD patients contained SP.

Whole Grain Foods and Heart Disease Risk

Coronary heart disease (CHD) is the leading cause of death in most developed nations and is rapidly increasing in prevalence in developing countries. Death rates from cardiovascular disease exceed 1 million annually in the United States and account for the largest disease-related cost to health with total costs estimated to exceed

Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment

120 billion per annum. Many dietary factors, including total and saturated fat consumption, fruit and vegetable intake and dietary fiber, have been shown to contribute to risk for CHD. We have systematically reviewed literature from the past 20 years evaluating an association between dietary fiber and CHD. Foods that are rich in dietary fiber, including fruits, vegetables, legumes and whole grain cereals, also tend to be a rich source of vitamins, minerals, phytochemicals, antioxidants and other micronutrients. Each of these factors may be independently contributing to the cardiovascular protective effects of fiber-rich foods.

Critical decline in fine motor hand movements in human aging

Multiple studies demonstrate that the brain in Alzheimers disease (AD) contains extensive oxidative damage. Most of these studies used advanced‐stage AD patients raising the question of whether oxidative damage is a late effect of neurodegeneration or precedes and contributes to the pathogenesis of AD. Here we describe F2‐isoprostane (F2‐IsoP) and F4‐neuroprostane (F4‐NP) levels in longitudinally followed, well documented autopsied normal control subjects and patients with amnestic mild cognitive impairment (MCI), and late‐stage AD. Gas chromatography/negative ion chemical ionization/mass spectrometry was used to determine F2‐IsoP and F4‐NP levels. Significant increases in F2‐IsoP levels were found in frontal, parietal and occipital lobes in MCI and late AD compared to controls but no significant differences were present between MCI and late AD. A significant increase in F4‐NPs was present in parietal and occipital lobes in MCI compared to controls and a significant increase was present in these regions and hippocampus in late AD compared to controls. The only difference betwen MCI and late AD was significantly increased F4‐NP in hippocampus in late AD. Our data indicate that lipid peroxidation is present in the brain of MCI patients and suggest that oxidative damage may play a role in the pathogenesis of AD. Ann Neurol 2005;58:730–735

Lifelong Bilingualism Maintains Neural Efficiency for Cognitive Control in Aging

BACKGROUND Slowing of motor movements in human aging is a well-known occurrence, but its biologic basis is poorly understood. Reliable quantitation may refine observations of this phenomenon to better aid research on this entity. METHODS A panel equipped with timing sensors under computer control was used to measure upper extremity movement times in two groups of healthy individuals: adults younger than 60 years of age (n = 56; range, 18-58 years) and adults older than 60 years of age (n = 38; range, 61-94 years). RESULTS Fine motor performance was better in the dominant hand (p = 0.0007) regardless of age. Adult and aged groups differed on two basic timing measures, which reflect coarse motor and fine motor performance (p < 0.0001). There were no gender differences on either measure. There was a strong effect of task difficulty with age on coarse motor (p < 0.01) and fine motor (p < 0.0001) measures. The fine motor measure of hand performance in healthy individuals correlated in a nonlinear fashion with age for more difficult tasks (r2 = 0.63) but showed a simple linear relation for less-demanding tasks (r2 = 0.5). CONCLUSION This technique sensitively detects age-related motor performance decline in humans. There may be a critical period in late midlife when fine motor performance decline either begins or abruptly worsens.

Altered brain activation in cognitively intact individuals at high risk for Alzheimer’s disease

Recent behavioral data have shown that lifelong bilingualism can maintain youthful cognitive control abilities in aging. Here, we provide the first direct evidence of a neural basis for the bilingual cognitive control boost in aging. Two experiments were conducted, using a perceptual task-switching paradigm, including a total of 110 participants. In Experiment 1, older adult bilinguals showed better perceptual switching performance than their monolingual peers. In Experiment 2, younger and older adult monolinguals and bilinguals completed the same perceptual task-switching experiment while functional magnetic resonance imaging (fMRI) was performed. Typical age-related performance reductions and fMRI activation increases were observed. However, like younger adults, bilingual older adults outperformed their monolingual peers while displaying decreased activation in left lateral frontal cortex and cingulate cortex. Critically, this attenuation of age-related over-recruitment associated with bilingualism was directly correlated with better task-switching performance. In addition, the lower blood oxygenation level-dependent response in frontal regions accounted for 82% of the variance in the bilingual task-switching reaction time advantage. These results suggest that lifelong bilingualism offsets age-related declines in the neural efficiency for cognitive control processes.