Online newspaper of professor Yasser Metwally

The author: Professor Yasser Metwally

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INTRODUCTION

May 31, 2008 — When other factors are controlled, people who consume mild to moderate amounts of alcohol tend to have a lower risk of metabolic syndrome than nondrinkers, according to a study in the December 2004 issue of Diabetes Care. [1]

A group of researchers from Boston University and the Framingham Heart Study [1] analyzed data from 8,125 participants in the Third National Health and Nutrition Examination Survey (NHANES III). Each subject was evaluated for components of metabolic syndrome—a cluster of symptoms including low serum HDL cholesterol, elevated triglycerides, hyperglycemia, hypertension, central obesity, and insulin resistance.

After adjusting for age, sex, physical activity, diet, and other variables, researchers [1] found that those who consumed 1 to 19 alcoholic drinks per month had a one-third lower risk of having metabolic syndrome, while those who consumed more than 20 drinks a month had about 66% lower prevalence of the syndrome.

While the observation was consistent across all ethnicities, the difference was most striking among white men and women, according to researchers. The consumption of alcohol was inversely proportional to low serum HDL cholesterol, elevated serum triglycerides, waist circumference, and high blood insulin levels.

On the other hand Baik and Shin found that Heavy drinking, in particular among liquor drinkers, is associated with an increased risk of the metabolic syndrome by influencing its components. [2]

References

1- Frieberg MS, Carbal HJ, Heeren TC, et al.: Alcohol consumption and the prevalence of the metabolic syndrome in the U.S. Diabetes Care 27:2954–2959, 2004. [Full text]

[2] Baik I, Shin C: Prospective study of alcohol consumption and metabolic syndrome. Am J Clin Nutr. 2008 May;87(5):1455-63 [Abstract]

The author: Professor Yasser Metwally

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INTRODUCTION

May 30, 2008 — Metabolic syndrome is highly prevalent in the U.S. (age-adjusted prevalence of 23.7%) (1) (2). This syndrome is well documented to increase the risk for developing type 2 diabetes and cardiovascular/cerebrovascular diseases (CVDs) and is associated with an all-cause mortality (3–5). Physical inactivity, excessive weight gain, high alcohol intake, and certain dietary factors have been identified as important modifiable risk factors for metabolic syndrome and its consequences (2,6,7).

In men with and without clinically manifest cardiovascular/cerebrovascular disease, smoking is associated with a metabolic profile indicating a higher degree of insulin resistance.

Smoking is also a strong risk factor for atherosclerosis and CVD, with a dose-dependent relationship (8). Smokers have abnormalities in lipoprotein metabolism (9) and endothelial function (10). Moreover, there is some evidence that smokers are at greater risk than nonsmokers of becoming insulin resistant and hyperinsulinemic (11,12). Thus, based on these findings, smoking may be considered as an important modifiable risk factor for metabolic syndrome. However, this relationship has not been clarified, and reports on this issue are also scarce.

References

1. Ford ES, Giles WH, Dietz WH: Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287:356–359, 2002

2. Yoon YS, Oh SW, Baik HW, Park HS, Kim WY: Alcohol consumption and the metabolic syndrome in Korean adults: the 1998 Korean National Health and Nutrition Examination Survey. Am J Clin Nutr 80:217–224, 2004

3. Hanson RL, Imperatore G, Bennett PH, Knowler WC: Components of the “metabolic syndrome” and the incidence of type 2 diabetes. Diabetes 51:3120–3127, 2002

4. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24:683–689, 2001

5. Lakka H-M, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288:2909–2916, 2002

6. Carnethon MR, Loria CM, Hill JO, Sidney S, Savage PJ, Liu K: Risk factors for the metabolic syndrome: the Coronary Artery Risk Development in Young Adults (CARDIA) study, 1985–2001. Diabetes Care 27:2707–2715, 2004

7. Yoo S, Nicklas T, Baranowski T, Zakeri IF, Yang SJ, Srinivasan SR, Berenson GS: Comparison of dietary intakes associated with metabolic syndrome risk factors in young adults: the Bogalusa Heart Study. Am J Clin Nutr 80:841–848, 2004

8. Kannel WB: Update on the role of cigarette smoking in coronary artery disease. Am Heart J 101:319–328, 1981

9. Kong C, Nimmo L, Elatrozy T, Anyaoku V, Hughes C, Robinson S, Richmond W, Elkeles RS: Smoking is associated with increased hepatic lipase activity, insulin resistance, dyslipidaemia and early atherosclerosis in type 2 diabetes. Atherosclerosis 156:373–378, 2001

10. Heitzer T, Yla-Herttuala S, Luoma J, Kurz S, Munzel T, Just H, Olschewski M, Drexler H: Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia: role of oxidized LDL. Circulation 9:1346–1353, 1996

11. Facchini FS, Hollenbeck CB, Jeppesen J, Chen YD, Reaven GM: Insulin resistance and cigarette smoking. Lancet 339:1128–1130, 1992[

12. Ronnemaa T, Ronnemaa EM, Puukka P, Pyorala K, Laakso M: Smoking is independently associated with high plasma insulin levels in nondiabetic men. Diabetes Care 19:1229–1232, 1996

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

May 29, 2008 — Despite recent advances in molecular genetics, it has proven very difficult to arrive at an accurate and clinically useful classification of the muscular dystrophies. Much of this difficulty arises from confusion related to the term “muscular dystrophy” itself, as well as a general reluctance on the part of the neuromuscular community to abandon traditional, clinically based classifications. Nevertheless, advances in the understanding of the molecular defects of these disorders have permitted a foundation for classification based on molecular biology. This review presents a historical perspective on the classification of the muscular dystrophies, and furnishes the underpinnings of a genetic classification that can be used both at the bedside and in the research laboratory.

Since the initial clinical descriptions of Duchenne muscular dystrophy in the mid 19th century, a precise classification of the group of diseases known as the muscular dystrophies has proven elusive. This is due to several factors, not the least of which is confusion over name “muscular dystrophy” itself. Since Erb first introduced the term in 1891, it has come to refer to a group of genetically-determined, progressive, degenerative disorders of muscle.[1] While this definition seems straight forward, there are many practical difficulties associated with using such a simple characterization. For example, several disorders, such as the congenital myopathies like central core disease and nemaline myopathy, have traditionally not been classified as muscular dystrophies because of their unique pathology, despite the fact that they are muscle genetic disorders, that can even prove progressive in certain patients. Similarly, many of the mitochondrial disorders, including the group of diseases subsumed under the term “progressive external ophthalmoplegia,” could also fulfill these criteria.[2] As recently as 1988, the mitochondrial myopathies were listed with the muscular dystrophies in the classification of neuromuscular disorders, established by the World Federation of Neurology Research Group on Neuromuscular Diseases.[3]

Conversely, several disorders which have traditionally been considered muscular dystrophies do not technically fit the definition provided above. It is certainly unclear, for example, whether disorders such as myotonic dystrophy are “degenerative” in the usual sense. In fact, myotonic dystrophy differs in so many ways from the more traditional forms of muscular dystrophy (such as Duchenne and facioscapulohumerol dystrophy), that it is often discussed with the other myotonic disorders in textbooks and monographs. Similarly, some of the “congenital” muscular dystrophies may be so slowly progressive (or non-progressive) that this factor cannot be used in diagnosing or classifying an individual patient. Finally, the term “degenerative,” which has traditionally implied that a condition may be idiopathic, is becoming a less appropriate term to use in conditions where the molecular pathogenesis is being clearly elucidated, as in Duchenne dystrophy and many of the limb-girdle syndromes.

Another difficulty in classifying the muscular dystrophies reflects the underlying problems inherent in the evolution of the classification of any genetic condition. Such schemes of necessity begin with clinical descriptions of individual disease entities, which have traditionally been identified with eponyms, reflecting the investigators who initially describe the condition. As more cases are reported, the clinical and pathologic limits of each condition are established, often with much overlap due to the lack of a “gold standard” for establishing each diagnosis. As larger families are reported, attempts are made to classify the diseases according to classic mendalian inheritance, an often-limited approach because of the significant phenotypic and genotypic variability within each condition. Finally, in the current “genetic era,” attempts are made to identify the specific genetic abnormality associated with each disease with the hope that such determinations can lead to a precise classification based on the individual gene defects.

The history of the classification of human muscular dystrophy follows exactly this pattern. By the early part of this century, the pioneering work by Duchenne, Gowers, Landouzy, Dejerine, Leyden, Möbius, Steinert, and others led to excellent clinical descriptions of most of the major types of muscular dystrophy.[4] Subsequently, in the middle of this century, several investigators, most notably Tyler and Wintrobe, Stevenson, Chung and Morton, and Walton and Nattrass, reported on their experience with large groups of patients and attempted to organize the numerous eponymous diseases into a coherent classification.[5-8] The efforts of Walton and Nattrass to classify all of the myopathic disorders are particularly noteworthy, both in the completeness of their review of the prior literature, and in their comprehensive discussion of the rationale for their proposed classification (Table 1).[8] It is a tribute to the clinical acumen of these investigators that many elements of their classification are retained in current “genetic era” classifications. Of particular note was the recognition by these investigators of three principal types of muscular dystrophy: Duchenne dystrophy, facioscapulohumeral dystrophy, and limb-girdle dystrophy. Although many modifications to this basic scheme would be proposed over the next 30 years, most included the basic structure and format initially proposed by Walton and Nattrass.[2,9-11]

Table 1. List of Myopathies According to the Classification of Walton and Nattrass^[8]

The author: Professor Yasser Metwally

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INTRODUCTION

May 29, 2008 — In a cohort of healthy older men and women, dehydroepiandrosterone (DHEA) was no different from placebo in reducing the risk for cognitive decline, according to the results of a double-blind, randomized controlled clinical trial reported in the May 14 Online First issue of the Journal of the American Geriatrics Society.

“Epidemiological studies in humans generally report that higher serum DHEA levels are associated with feelings of well-being, better cognitive function, and improvement over time in long-term memory, whereas lower DHEA levels are associated with depressed mood, lower life satisfaction, and poorer cognitive function,” write Donna Kritz-Silverstein, PhD, from the University of California at San Diego in La Jolla, and colleagues from the DHEA and Well-Ness Trial. “Early, open-label clinical trials reported improvement in libido, well-being, mood, and verbal memory after DHEA treatment. In contrast, the few previous double-blind clinical trials examining the effects of DHEA supplementation on cognitive function and aspects of well-being yield inconsistent results.”

The goal of this study was to evaluate the effect of 50 mg of daily oral DHEA replacement for 1 year on cognitive function and quality of life, including life satisfaction, mood, and sexuality, in healthy older adults not selected for lower levels of DHEA.

At a clinical research facility, 110 men and 115 women aged 55 to 85 years (mean age, 68 ± 8 years) were randomized to receive 50 mg of daily oral DHEA or placebo for 1 year.

Outcome measures were 6 cognitive function tests performed at baseline and at 12 months and the Beck Depression Inventory (BDI), the Medical Outcomes Study 36-Item Short-Form Survey (SF-36), the Life Satisfaction Index-Z, the Satisfaction with Life Scale, and the Female Sexual Function Index (in women) or the 15-item International Index of Erectile Function (in men) at baseline and at 3, 6, and 12 months.

Change in cognitive function with time was not significantly different between the DHEA and placebo groups (P >.10). During the 1-year trial, BDI scores decreased for men (P =.006) and women (P = .02), and Satisfaction with Life Scale scores increased for women (P =.004). However, the DHEA and placebo groups did not differ with time on these measures or on the SF-36, Life Satisfaction Index-Z scale, or sexual function scales (P >.10).

“DHEA supplementation has no benefit on cognitive performance or well-being in healthy older adults, and it should not be recommended for that purpose in the general population,” the study authors write.

Limitations of this study include participants limited to healthy men and women without cognitive impairment or depression.

“This study of healthy older men and women who were not selected for endogenous DHEA levels failed to show any benefits from DHEA supplementation for 1 year on cognitive function, mood, quality of life, or sexual function,” the study authors write. “These results were observed despite restoration of youthful DHEA levels in men and women and enhancement of estrogens and testosterone in women. Although it is unknown whether DHEA supplementation may benefit specific subgroups of men and women, such as those who are clinically depressed or cognitively impaired, the present results suggest that DHEA supplementation should not be recommended for enhancement of cognition or well-being in the general population.”

The National Institutes of Aging and National Center for Research Resources supported this study. The study authors have disclosed no relevant financial relationships.

• Clinical Context

DHEA and its sulfate (DHEAS) are abundantly found in circulating steroid hormones. Levels peak at ages 20 to 30 years then decline with age, and perimenopausal women have only 50% of the peak levels declining to 20% at age 70 years. Higher serum DHEA levels have correlated with feelings of well-being, improved cognitive function, and improvement in memory, but trials so far have been open label with small sample sizes. DHEA is available over the counter in the United States and is often used as a preventive agent for chronic diseases or in the improvement of well-being, memory, and cognitive function.

This is a randomized, double-blind clinical trial to examine the effect of 1 year of DHEA 50 mg of daily supplementation on performance on a battery of cognitive tests and quality-of-life measures in older adults not selected for preexisting low levels of DHEA.

• Study Highlights

  1. Included were 110 men and 115 women who were healthy, community dwelling, and aged 55 to 85 years who were nonsmokers and were not currently using any hormone therapy.

  2. Patients had blood samples drawn for measurement of sex hormone levels and medical and health history at baseline and were observed at 3, 6, and 12 months.

  3. A trained interviewer administered a battery of standardized cognitive function tests to assess multiple aspects of cognitive function.

  4. The Modified Mini-Mental State Examination had scores of 0 to 100 (higher scores mean better performance).

  5. The Trail Making Test Part B was used for testing visuomotor tracking.

  6. The Modified Boston Naming and the Category Fluency tests were also administered.

  7. The Word List Memory and Word List Recall tests were used for memory testing.

  8. The 21-item BDI was used for depression screening.

  9. 2 indices from the SF-36 were used for quality of life.

  10. Self-reported sexual functioning was assessed by the 19-item Female Sexual Function Index for women and the 15-item International Index of Erectile Dysfunction for men.

  11. Mean age was 68.7 years, mean years of education were 16.7 years, and mean age of menopause was 50 years for women.

  12. Baseline serum testosterone and DHEA levels were higher in women randomized to receive treatment vs those randomized to receive placebo.

  13. At 12 months, mean compliance was 95% for the DHEA group and 94% for the placebo group.

  14. DHEA treatment significantly increased circulating DHEA and DHEAS levels in men and women, with levels reaching 2 to 4 times higher than baseline and maintained throughout the trial.

  15. Testosterone increased 60% and estradiol 40% in women receiving DHEA, but no changes were seen in men.

  16. Median scores for cognitive function tests tended to improve with time in the treatment group but remained the same or declined in the placebo group, although the differences were not statistically significant.

  17. Men and women both showed significant improvements in BDI score with time, but this was not statistically significantly different between the DHEA and placebo groups.

  18. Increases in life satisfaction were seen with time, but there was no difference between the DHEA and placebo groups.

  19. SF-36 scores improved for women with time, but there were no differences between the DHEA and placebo groups.

  20. Similar results were seen for comparisons of testosterone levels.

• Pearls for Practice

  1. Use of DHEA 50 mg daily is not associated with improvements in cognitive function in older men and women.

  2. Use of DHEA 50 mg daily in healthy, community-dwelling older men and women is not associated with improvements in quality of life.

References

1. J Am Geriatr Soc. Published online May 14, 2008.

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

May 29, 2008 — Cognition among people with heart disease declines over time, regardless of whether they undergo bypass surgery or receive alternative forms of treatment, according to a new study published in the May issue of the Annals of Neurology.

The 6-year observational study provides further evidence that the cognitive decline of heart patients is due to vascular disease that might be curbed by heart-healthy lifestyle practices such as diabetes management, being a nonsmoker, and blood-pressure control, said 1 of the study authors, Guy M. McKhann, MD, professor of neurology at Johns Hopkins University School of Medicine, in Baltimore, Maryland.

“We think these are people who have vascular disease of the brain going into the study, whether they’re in the surgery or nonsurgery group. I think we’re watching the progression of vascular disease of the brain over a 6-year period,” he said.

The finding could mean that the heart disease treatment pendulum, which began to swing in favor of stents after observations that surgery resulted in cognitive decline, might well swing back toward surgery, said Dr. McKhann.

• Back to Surgery?

The Johns Hopkins researchers compared the cognitive status of 152 patients undergoing elective or urgent coronary artery bypass grafting (CABG) and 92 cardiac patients receiving other treatments such as stents or pharmaceuticals.

The patients completed a medical history review and a battery of standardized neuropsychological tests at baseline, 3 months, 1 year, 3 years, and 6 years. Tests included the Mini Mental State Examination (MMSE), the Center for Epidemiological Studies Depression Scale (CES-D), and the Functional Status Questionnaire (FSQ). Among the functions observed were memory, motor speed, attention, and the ability to plan ahead. The investigators controlled for influences of education, age, and sex.

The 2 treatment groups began with about the same cognitive scores, and both showed improvements from baseline to 1 year. However, all patients experienced subsequent similar declines in performance for all cognitive domains. “We found no statistically significant or clinically meaningful differences in the degree of decline in cognitive test performance over time between the CABG patients and the nonsurgical comparison patients,” the authors wrote.

• Language and Memory Not Affected

Interestingly, unlike in Alzheimer’s disease, where memory is affected, the most striking areas of cognitive decline in these heart patients were those related to decision making — for example, tasks requiring speed of processing or speed of response — and those requiring executive function, said Dr. McKhann. “Things like language and memory are not particularly affected” in these groups, he said.

In comparing the degree of cognitive change in the 2 groups, the authors stated that for the CABG patients, the only statistically significant declines were in visuoconstruction — for example, naming common items from pictures (P < .01) — and executive function (P = .02). For the nonsurgical group, declines were statistically significant in visuoconstruction (P < .01) and motor speed (P = .01).

For MMSE performance, mean scores at baseline and at 72 months were similar in the 2 groups. At baseline, 5% of the CABG and 6% of the nonsurgical patients had MMSE scores below normal (< 24). From baseline to 72 months, the average within-patient change on the MMSE was a decline of 0.22 for the CABG group and 0.16 points for the nonsurgical patients.

The results of this research could mean an increase in cardiac surgery, Dr. McKhann said. In recent years, many doctors veered away from surgical interventions after observational evidence pointed to its negative effect on cognition; 1 study found that 40% of people treated with CABG had significant cognitive decline, said Dr. McKhann.

Many believed the culprit was the pump used during bypass surgery. “The pendulum swung way over to the stents for awhile, 1 of the arguments being that if you have heart surgery, you’re hurting your brain, but now we’re saying that that evidence isn’t there,” said Dr. McKhann. “There may be reasons for choosing the stent, but that [cognitive decline with surgery] isn’t one of them.”

• Safety of Stents Questioned

Another argument for revisiting the surgical approach is that the long-term safety of stents is now being questioned, added Dr. McKhann.

The study highlights the need to examine the impact on the brain, as well as the heart, of risk factors such as smoking, uncontrolled diabetes, and high blood pressure. “We have always been thinking in terms of the heart; if we do this [particular behavior] we prevent heart attacks and deaths, but what about the brain?” said Dr. McKhann. “What helps the heart helps the brain.”

This study is part of continuing research involving 4 groups (the other 2 are patients undergoing off-pump heart surgery and heart-healthy controls). The already-published 3-year data on all groups uncovered evidence that all heart patients have some degree of cognitive decline compared with heart-healthy controls, which could be attributed to cerebral vascular disease, said Dr. McKhann.

References

1. Ann Neurol. 2008;63:581-590.Abstract

The author: Professor Yasser Metwally

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INTRODUCTION

May 28, 2008 — Acute seizures are associated with a higher mortality at 30 days after stroke, according to the results of a population-based study reported online in the January 31 issue of Epilepsia and will appear in the June 2008 print issue.

“Cerebrovascular disease has long been recognized as a risk factor for the development of epilepsy and it is considered the most common identified antecedent condition that results in symptomatic epilepsy in the elderly,” write Jerzy P. Szaflarski, from the University of Cincinnati Academic Health Center in Ohio, and colleagues. “The incidence of seizures within 24 h of acute stroke has not been studied extensively. We aimed to establish the incidence of acute poststroke seizures in a biracial cohort and to determine whether acute seizure occurrence differs by race/ethnicity, stroke subtype, and/or stroke localization.”

The investigators identified all stroke cases occurring between July 1993 and June 1994 and in 1999 in the population of the greater Cincinnati metropolitan region, after excluding patients with a previous history of seizures or epilepsy.

Of 6044 patients who had a stroke and who had no previous history of seizure, 190 (3.1%) had seizures within the first 24 hours of stroke onset. Among patients with intracerebral hemorrhage or subarachnoid hemorrhage, 8.4% had a seizure within the first 24 hours of stroke onset (P = .0001) compared with all other stroke subtypes. For ischemic stroke, incidence of seizures was higher for cardioembolic stroke compared with small or large vessel ischemic stroke (P = .02).

Although patients with seizures had higher mortality than did patients without seizures (P < .001), seizures were not an independent risk factor for mortality at 30 days after stroke. Hemorrhagic stroke, younger age, and prestroke Rankin score of 1 or more were independent risk factors for seizure development, whereas race/ethnicity or ischemic stroke localization were not associated with risk for seizure development.

Limitations of this study include biracial population not including patients of Hispanic, Native American, or Asian ethnicity; retrospective data collection; and possible overestimation or underestimation of the incidence of seizures.

“The overall incidence of acute seizures after stroke was 3.1%, with a higher incidence seen in hemorrhagic stroke, younger patients, and those presenting with higher prestroke Rankin scores,” the study authors write. “Acute seizures were associated with a higher mortality at 30 days after stroke.”

• Clinical Context

Seizures occur in approximately 10% of patients after stroke, and half of these seizures occur during the first 1 to 2 weeks following stroke. The effect of these early seizures on the risk of mortality is controversial, as some research has demonstrated an increased risk of death associated with early seizures following stroke, and other studies have not. In a study by Kilpatrick and colleagues of 62 patients with stroke, published in the May 1992 issue of Archives of Neurology, patients with an early seizure after stroke experienced a 3-fold increase in the absolute risk of subsequent stroke compared with stroke patients without early seizure.

The current study focuses on the incidence of seizure within the first 24 hours after stroke, risk factors for seizure, and the prognosis after seizure.

• Study Highlights

  1. Study data were drawn from 19 hospitals in the Cincinnati metropolitan area. Patients with a billing code for stroke between 1993 and 1994 and in 1999 were included in the study, and patients admitted for transient ischemic attack were also part of the study. Only patients with clinical evidence of a stroke were included in the study.

  2. A study nurse examined patient charts for the occurrence of seizures during the first 24 hours after the onset of stroke symptoms. Risk factors in the patient history for seizure were examined.

  3. Researchers also assigned stroke category and the mechanism of stroke.

  4. The main study outcomes were the incidence of seizure within the first 24 hours after stroke, risk factors for seizure, and the prognosis after seizure.

  5. 6044 stroke events met criteria for the current study; 88.1% of patients had an ischemic event, and 11.8% had a hemorrhagic stroke.

  6. The incidence of poststroke seizures within 24 hours was 3.1%.

  7. Patients with seizures were younger and had a lower initial Glasgow Coma Scale score and a higher National Institutes of Health Stroke Scale score.

  8. The incidence rates of acute seizures among patients with ischemic and hemorrhagic stroke were 2.4% and 8.4%, respectively.

  9. Patients with cardioembolic stroke experienced a higher rate of seizures compared with patients with small or large vessel ischemic disease.

  10. The absolute rates of all-cause mortality at 30 days were 32.1% and 13.3% among patients with and without seizures, respectively. The presence of poststroke seizure increased the risk of 30-day mortality 2-fold, although early seizure was not an independent risk factor for 30-day mortality.

  11. On fully adjusted analyses, younger age, hemorrhagic stroke, and a prestroke Rankin score of 1 or more were significant and independent predictors of seizure occurrence within the first 24 hours after stroke, but race/ethnicity and the anatomic location of stroke were not.

• Pearls for Practice

  1. Seizures following stroke occur in approximately 10% of patients, with half of these seizures occurring during the first 2 weeks after stroke. Although early seizure after stroke may not independently predict an increased risk of mortality, early seizures do appear to predict an increased risk of subsequent seizures.

  2. In the current study, younger age, hemorrhagic stroke, and a prestroke Rankin score of 1 or more were significant and independent predictors of seizure occurrence within the first 24 hours after stroke, but race/ethnicity and the anatomic location of stroke were not.

References

1. Epilepsia. Published online January 31, 2008. 2008;00:000-000.

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

May 28, 2008 — Long-term results from 2 large European trials suggest that carotid artery stenting (CAS) is as effective as carotid endarterectomy (CEA) in preventing recurrent ischemic stroke in patients with severe, symptomatic carotid stenosis.

Presented here at the 17th European Stroke Conference (ESC), results from both the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) and the Stent-Protected Percutaneous Angioplasty of the Carotid Artery vs Endarterectomy (SPACE) studies reported strikingly similar results in terms of the long-term efficacy of the 2 procedures, despite the fact that in both studies, stenting had failed to meet noninferiority criteria vs endarterectomy in their primary analyses.

“The conclusion from the SPACE trial is exactly the same as the EVA-3S study. That is, if a patient has been treated successfully without any complications, the [long-term] risk of a secondary stroke is very small and very comparable between these 2 modalities,” Peter A. Ringleb, MD, from Ruprecht-Karls-University, in Heidelberg, Germany, principal investigator of the SPACE study, told reporters attending an ESC press conference.

• SPACE Results

Launched in 2001, the SPACE study is a randomized noninferiority trial that included 1214 patients from 37 centers in Germany, Switzerland, and Austria.

The goal of the study was to determine whether safety and efficacy of treatment for symptomatic carotid stenosis with CAS was equivalent to the standard approach of CEA.

The 30-day outcome results, which were published in 2006, failed to demonstrate noninferiority of the stenting procedure vs endarterectomy.

Here at the ESC, where the 2-year follow-up results were presented for the first time, the investigators found the rate of any periprocedural stroke or death, plus ipsilateral ischemic stroke within 2 years, was very similar, at 8.49% in the CEA group and 9.22% in the CAS group.

Furthermore, the investigators reported the absolute number of recurrent ischemic events after the periprocedural period at 2-year follow-up was low — 10 events after CEA (1.7%) and 12 after CAS (2.0%).

• Need for Improvement

The EVA-3S trial was also a randomized noninferiority study that was conducted at 30 centers in France and included 527 subjects. Launched in 2000, the study was stopped by the safety committee in 2005 due to a higher 30-day risk of stroke or death associated with stenting.

In 2006, within a week of the SPACE investigators publishing their findings, the EVA-3S researchers reported that the 30-day risk of any stroke was significantly greater for stenting — 9.6% for CAS vs 3.9% CEA. For disabling stroke, the rate at 30 days was 3.4% for stenting compared with 1.5% for endarterectomy.

However, the investigators continued to follow study subjects and found the rates of ipsilateral stroke from 31 days to 4 years were very low in both groups — 11.1% for CAS and 6.2% for CEA — a difference that was not statistically significant, said the study’s principal investigator, Jean-Louis Mas, MD, from the Hôpital Sainte-Anne, in Paris, France.

“Carotid stenting is as effective as carotid endarterectomy in preventing further ischemic stroke, but we need to improve the safety of the technique before it can become a widespread alternative to carotid endarterectomy in patients with symptomatic carotid stenosis,” said Dr. Mas.

Drs. Mas and Ringleb report no conflicts of interest. The EVA-3S study was supported by the French Department of Health. The SPACE study was supported by the Germany’s Federal Ministry of Education and Research, German Research Foundation, German Neurological Society, German Neuroradiological Society, Deutsche Röntgengesellschaft, Guidant, Boston Scientific, and Sanofi-Aventis.

References

1. 17th European Stroke Conference: Abstracts 4 and 5. Presented May 14, 2008.

The author: Professor Yasser Metwally

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INTRODUCTION

May 28, 2008 — In a population-based study of close to 100 children from Iceland who had unprovoked seizures in the first year of life, 13.7% went on to have an autism spectrum disorder (ASD).

Having symptomatic seizures (with a known cause) as opposed to nonsymptomatic or cryptogenic seizures (with an unknown cause) was associated with an almost 9-fold higher risk of subsequent autism.

Evald Saemundsen, PhD, from the division of autism and communication disorders, State Diagnostic and Counseling Center, in Kopavogur, Iceland, reported these findings in an oral presentation at the 7th Annual International Meeting for Autism Research.

“A history of seizure in the first year of life should attract attention to the possibility of subsequent ASD, particularly in cases where seizures are of symptomatic origin,” he said.

• Epilepsy and ASD

Epilepsy (recurrent, unprovoked seizures) was 1 of the first biological factors associated with autism, Dr. Saemundsen noted. Cases studies have reported a high prevalence of autism in children with previous infantile spasms, a type of epilepsy. But it was unknown whether other unprovoked seizures in the first year of life present a risk of ASD.

The researchers aimed to determine whether there was a link between unprovoked seizures in the first year of life and ASD.

They examined hospital records from 1982 to 1998 to identify all pediatric patients in Iceland who had been diagnosed with seizures during their first year of life.

Of the 121 children they identified, 5 had died and 1 lived abroad. The parents of the remaining 115 children were contacted, and 95 parents consented to allow their children — 61 girls and 34 boys, with a mean age of 11 years — to participate in the study.

The parents replied to the social communication questionnaire, which was used as an initial test of the children’s autistic behaviors. The children were then assessed using the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) and/or the Childhood Autism Rating Scale (CARS).

Of the 95 children, 17 had infantile spasms and 78 had other types of seizures.

A total of 13 children — 8 girls and 5 boys — had ASD. All but 1 had intellectual disability, and 6 had profound intellectual disability (IQ < 20).

Of the 13 children with ASD, 6 had infantile spasms, and 7 had other types of epilepsy. The children with infantile spasms were more likely to have subsequent ASD than were children with other types of epilepsy (odds ratio, 1.55; 95% CI, 0.33 – 7.37).

• Symptomatic Seizures Strongly Predicted ASD

Children with seizures of symptomatic origin, irrespective of type, were nearly 9 times more likely to develop ASD than were those who had nonsymptomatic seizures (OR, 8.73; 95% CI, 1.88 – 40.54).

The high prevalence of ASD (13.7%) in children with unprovoked seizures in the first year of life that was found in this study warrants further investigation, said Dr. Saemundsen.

References

1. 7th Annual International Meeting for Autism Research: Oral Presentation 113.7. May 15-17, 2008.

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

May 28, 2008 — Patients with severe symptomatic carotid stenosis treated with endovascular therapy (percutaneous transluminal angioplasty and stenting) appear to have higher restenosis rates than their counterparts treated with carotid endarterectomy.

However, the investigators note, the higher restenosis rates among the endovascular group held true only for people treated with angioplasty alone and did not apply to those who received stents.

Long-term follow-up results from the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), presented here at the 17th European Stroke Conference, showed that the cumulative risk for carotid restenosis or occlusion in patients treated with endovascular therapy or endarterectomy was 34% and 14%, respectively.

“Restenosis was significantly more frequent after angioplasty than after endarterectomy. We did not detect a significantly higher risk for restenosis among stented than among endarterectomy patients,” study investigator Leo H. Bonati, MD, from the University College of London Institute of Neurology, in the United Kingdom, told conference attendees.

Designed to compare the risks and benefits of endovascular therapy with those of surgical intervention, CAVATAS randomized 504 patients with carotid stenosis to either endovascular treatment — with or without stenting — or carotid endarterectomy.

• Little Change Over Time

The 1-year study results, which were published in the Lancet in 2001 (357:1729-1737), showed that the 2 treatments carried a similar risk for disabling stroke or death at 30 days. However, at 1-year follow-up, the investigators found that ipsilateral carotid stenosis was more common after endovascular than after surgical treatment (14% vs 4%).

To determine whether the difference in restenosis persisted during long-term follow-up, the investigators followed study subjects for up to 8 years after randomization.

The researchers compared the cumulative risks for restenosis in both treatments. They looked at the impact of the baseline degree of carotid stenosis on restenosis (= 70% and < 70%).

Within the endovascular group, investigators examined whether stents were more effective than angioplasty in preventing restenosis. The investigators also looked at independent predictors of restenosis and whether restenosis contributed to cerebrovascular events.

Patients with completed endovascular therapy or endarterectomy and subsequent duplex ultrasound were included in the study.

Ultrasound follow-up was available in 196 patients in the endovascular group and 217 patients in the endarterectomy group. According to Dr. Bonati, there were no significant differences in baseline characteristics between the 2 patient groups, including age, sex, prevalence of diabetes, hypertension, hypercholesterolemia, and smoking.

• Stenting Comparable to Endarterectomy

In both groups, the mean degree of stenosis before treatment was about 85% and the median duration of available ultrasound follow-up was about 4 years.

A total of 54 patients in the endovascular therapy group went on to develop restenosis during follow-up, compared with 19 patients in the surgery group. Therefore, said Dr. Bonati, the cumulative risk of developing restenosis was significantly higher in the endovascular group than in the surgery group, with a hazard ratio of 3.6.

When researchers looked at the 2 endovascular subgroups, they found that the majority of patients (146) were treated with angioplasty alone and, of these individuals, 47 experienced restenosis. In comparison, 50 patients received stents and, of these, 7 experienced restenosis at 8-year follow-up.

“Compared with surgery, those who were treated with balloon angioplasty alone had a significantly elevated risk of restenosis — 39% vs 17% for stenting,” said Dr. Bonati.

He also pointed out that the restenosis rate among people who received endovascular treatment with stents was comparable to the rate (14%) of cumulative risk in the endarterectomy group.

• Smoking Independent Restenosis Risk Factor

When the investigators looked at independent risk factors for restenosis, they found that individuals who smoked at baseline or who had smoked in the past had more than a 3-fold increased risk for restenosis.

However, restenosis was not predicted by age, sex, the presence of vascular risk factors, high blood pressure, peripheral artery disease, coronary heart disease, or the degree of stenosis before treatment.

The study had 2 primary end points. The first was a combined outcome of ipsilateral stroke, transient ischemic attack, and amaurosis fugax. There was also a single end point of ipsilateral stroke alone.

A total of 52 patients in the study population had a diagnosis of restenosis within the first year of treatment. Of these individuals, 10 went on to have the combined end point. In comparison, 27 patients in the study group who were free of restenosis within 1 year went on to have the combined end point.

There appeared to be no increased risk for ipsilateral stroke among patients with first-year restenosis, compared with those who were free of restenosis within the first year of treatment.

According to Dr. Bonati, carotid stenting has largely replaced balloon angioplasty as the treatment of choice for symptomatic carotid stenosis.

References

1. 17th European Stroke Conference. Presented May 15, 2008