News Roundup: New and Noteworthy Information

Carotid artery stenting is as efficacious as endarterectomy for the prevention of recurrent ipsilateral ischemic stroke, but safety concerns during the 30-day period following surgery need to be addressed, according to two studies in the October Lancet Neurology. In the Stent-Protected Angioplasty versus Carotid Endarterectomy study, patients underwent either carotid angioplasty with stenting (n = 613) or carotid endarterectomy (n = 601). After two years, the rate of recurrent ipsilateral ischemic stroke was similar in both treatment groups. In the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis trial, researchers compared outcome after stenting with outcome after endarterectomy after four years in 527 subjects who had carotid stenosis of at least 60% that had recently become symptomatic. The probability of periprocedural stroke or death and nonprocedural ipsilateral stroke was higher in those who received stenting than in those who received endarterectomy (11.1% vs 6.2%, respectively; hazard ratio, 1.97). The differences were attributed to “the higher periprocedural risk of stenting compared with endarterectomy,” said the researchers. After the periprocedural period, however, risks for ipsilateral stroke were similar in both treatment groups.

Fetal aneuploidy can be detected using a noninvasive maternal blood test, according to a study in the October 21 Proceedings of the National Academy of Sciences. Researchers used high-throughput shotgun technology to sequence cell-free DNA from the plasma of pregnant women, obtaining an average of five million sequence tags per patient sample. “The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy,” the investigators stated. Nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edwards syndrome), and one case of trisomy 13 (Patau syndrome) were observed among 12 women with aneuploid pregnancies and six women with normal pregnancies. Trisomy was detected as early as the 14th week of gestation. “Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA,” the study authors added, “and we found evidence that this DNA is enriched for sequences from nucleosomes.”

The FDA has approved two new dosage strengths for Stalevo (carbidopa, levodopa, and entacapone) tablets: 75 (18.75 mg of carbidopa, 75 mg of levodopa, and 200 mg entacapone) and 125 (31.25 mg of carbidopa, 125 mg of levodopa, and 200 mg of entacapone). The new dosage strengths are in addition to the already existing Stalevo 50, 100, 150, and 200 tablets. Stalevo is indicated for patients with Parkinson’s disease who experience end-of-dose “wearing off.” It combines levodopa with the enzyme inhibitors carbidopa and entacapone to provide greater and more sustained levels of levodopa in the blood and improve bodily movement control. The most common side effects include dyskinesia, hypokinesia, hyperkinesia, nausea, diarrhea, discoloration of urine, sweat, and/or saliva, abdominal pain, dizziness, constipation, fatigue, pain, and hallucinations. Stalevo was originally approved by the FDA in June 2003 and is marketed by Novartis Pharmaceuticals Corporation in East Hanover, New Jersey.

Vitamin D deficiency may have a role in Parkinson’s disease, reported researchers in the October Archives of Neurology. Patients with Parkinson’s disease were matched by age to healthy controls and patients with Alzheimer’s disease. More patients with Parkinson’s disease (55%) had insufficient vitamin D, compared with controls (36%) and patients with Alzheimer’s disease (41%). The Parkinson’s disease subjects also had significantly lower mean plasma 25-hydroxyvitamin D concentration than the Alzheimer’s disease and control cohorts (31.9 vs 34.8 and 37.0 ng/mL, respectively). “Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of Parkinson’s disease,” suggested the investigators.

Treatment with valproic acid was associated with improved memory and reduced brain lesions in a mouse model, reported researchers in the October 27 online Journal of Experimental Medicine. Valproic acid decreased β-amyloid protein production by inhibiting glycogen synthase kinase 3β–mediated γ-secretase cleavage of β-amyloid precursor protein in vitro and in vivo. “Valproic acid treatment significantly reduced neuritic plaque formation and improved memory deficits in transgenic Alzheimer’s disease model mice,” observed the investigators. In addition, treatment with valproic acid in the early stages of Alzheimer’s disease alleviated memory deficits in the mice.

Education and occupation may reduce the severity and delay the clinical expression of Alzheimer’s disease, according to a study in the October 21 Neurology. The researchers assessed 242 patients with probable Alzheimer’s disease for the impact of education and occupation on brain glucose metabolism (rCMRglc) in patients with amnestic mild cognitive impairment (aMCI). A significant association was shown between higher education and occupation and lower rCMRglc in the posterior temporoparietal cortex and precuneus in those with probable Alzheimer’s disease and aMCI converters; no such correlation was found in aMCI nonconverters or the control group. “This study suggests that education and occupation may be proxies for brain functional reserve, reducing the severity and delaying the clinical expression of Alzheimer’s disease pathology,” the researchers concluded.

A high level of physical activity is associated with less severe first stroke and improved long-term outcome, according to a report in the October 21 Neurology. Researchers compiled data on 265 subjects (mean age, 68) who represented a subset of patients with first-ever stroke enrolled in the ExStroke Pilot Trial. Prestroke level of physical activity was measured retrospectively using the Physical Activity Scale for the Elderly questionnaire. Stroke severity was measured with the Scandinavian Stroke Scale, and long-term outcome was assessed after two years with the modified Rankin Scale. Patients in the lowest quartile of physical activity had the poorest outcome, as well as a more severe stroke. Higher physical activity was associated with a less severe stroke (odds ratio [OR], 2.54) and a decreased likelihood of poor long-term outcome (OR, 0.46).

Multiplex ligation-dependent probe amplification (MLPA) is an efficient and inexpensive tool for screening chromosomal abnormalities present in autism spectrum disorders, researchers reported in the October BMC Medical Genomics. A screening of 279 unrelated subjects showed duplications of the ­15q11-q13 region in two subjects, as well as duplications of the 22q11 region in two subjects. In an additional two patients, smaller de novo duplications were identified. Genes in these novel duplications included GABRB3 and ATP10A in one case and MKRN3, MAGEL2, and NDN in the other. These duplications likely exacerbate symptoms and/or increase liability for autism spectrum disorders. The researchers also found a partial duplication of the ASMT gene in 6% to 7% of cases, compared with 2% of controls, indicating that further study is needed to determine its potential impact on autism spectrum disorders. “MLPA proves to be an efficient method to screen for chromosomal abnormalities,” they stated.

Brain microbleeds are more prevalent in black patients than in white patients, according to a report in the October 7 Neurology. A total of 87 subjects (42 black, 45 white) with intracerebral hemorrhage (ICH) were analyzed. Black subjects were younger and had a greater rate of hypertension but did not have other vascular risk factors. Seventy-four percent of black patients had one or more microbleeds, compared with 42% of white patients. “The black population also tended to have a greater frequency of microbleeds in multiple territories than the white population (38% vs 22%),” the researchers observed. Race remained an independent predictor of microbleeds (odds ratio, 3.3), after adjusting for age, hypertension, and alcohol use. “Microbleeds may be an important emerging imaging biomarker with the potential to provide insights into ICH pathophysiology, prognosis, and disease progression,” the investigators concluded.

Patients with acute ischemic stroke who require aggressive measures to lower blood pressure should not be excluded from receiving intravenous t-PA therapy, according to a study in the September Archives of Neurology. Medical records of 178 patients with acute ischemic stroke who were treated with t-PA therapy were reviewed. Fifty patients required blood pressure–lowering treatment before receiving t-PA therapy; of these, 24 patients received nicardipine as first-line therapy or after receiving labetalol. There were no significant differences in adverse events between those treated with nicardipine or labetalol and those who did not receive blood pressure–lowering treatment. “Data suggest that patients with acute ischemic stroke requiring aggressive treatment to lower blood pressure should not be excluded from receiving t-PA therapy,” the authors concluded, noting that a prospective study is needed.

Carotid artery stenting is as efficacious as endarterectomy for the prevention of recurrent ipsilateral ischemic stroke, but safety concerns during the 30-day period following surgery need to be addressed, according to two studies in the October Lancet Neurology. In the Stent-Protected Angioplasty versus Carotid Endarterectomy study, patients underwent either carotid angioplasty with stenting (n = 613) or carotid endarterectomy (n = 601). After two years, the rate of recurrent ipsilateral ischemic stroke was similar in both treatment groups. In the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis trial, researchers compared outcome after stenting with outcome after endarterectomy after four years in 527 subjects who had carotid stenosis of at least 60% that had recently become symptomatic. The probability of periprocedural stroke or death and nonprocedural ipsilateral stroke was higher in those who received stenting than in those who received endarterectomy (11.1% vs 6.2%, respectively; hazard ratio, 1.97). The differences were attributed to “the higher periprocedural risk of stenting compared with endarterectomy,” said the researchers. After the periprocedural period, however, risks for ipsilateral stroke were similar in both treatment groups.

Fetal aneuploidy can be detected using a noninvasive maternal blood test, according to a study in the October 21 Proceedings of the National Academy of Sciences. Researchers used high-throughput shotgun technology to sequence cell-free DNA from the plasma of pregnant women, obtaining an average of five million sequence tags per patient sample. “The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy,” the investigators stated. Nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edwards syndrome), and one case of trisomy 13 (Patau syndrome) were observed among 12 women with aneuploid pregnancies and six women with normal pregnancies. Trisomy was detected as early as the 14th week of gestation. “Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA,” the study authors added, “and we found evidence that this DNA is enriched for sequences from nucleosomes.”

The FDA has approved two new dosage strengths for Stalevo (carbidopa, levodopa, and entacapone) tablets: 75 (18.75 mg of carbidopa, 75 mg of levodopa, and 200 mg entacapone) and 125 (31.25 mg of carbidopa, 125 mg of levodopa, and 200 mg of entacapone). The new dosage strengths are in addition to the already existing Stalevo 50, 100, 150, and 200 tablets. Stalevo is indicated for patients with Parkinson’s disease who experience end-of-dose “wearing off.” It combines levodopa with the enzyme inhibitors carbidopa and entacapone to provide greater and more sustained levels of levodopa in the blood and improve bodily movement control. The most common side effects include dyskinesia, hypokinesia, hyperkinesia, nausea, diarrhea, discoloration of urine, sweat, and/or saliva, abdominal pain, dizziness, constipation, fatigue, pain, and hallucinations. Stalevo was originally approved by the FDA in June 2003 and is marketed by Novartis Pharmaceuticals Corporation in East Hanover, New Jersey.

Vitamin D deficiency may have a role in Parkinson’s disease, reported researchers in the October Archives of Neurology. Patients with Parkinson’s disease were matched by age to healthy controls and patients with Alzheimer’s disease. More patients with Parkinson’s disease (55%) had insufficient vitamin D, compared with controls (36%) and patients with Alzheimer’s disease (41%). The Parkinson’s disease subjects also had significantly lower mean plasma 25-hydroxyvitamin D concentration than the Alzheimer’s disease and control cohorts (31.9 vs 34.8 and 37.0 ng/mL, respectively). “Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of Parkinson’s disease,” suggested the investigators.

Treatment with valproic acid was associated with improved memory and reduced brain lesions in a mouse model, reported researchers in the October 27 online Journal of Experimental Medicine. Valproic acid decreased β-amyloid protein production by inhibiting glycogen synthase kinase 3β–mediated γ-secretase cleavage of β-amyloid precursor protein in vitro and in vivo. “Valproic acid treatment significantly reduced neuritic plaque formation and improved memory deficits in transgenic Alzheimer’s disease model mice,” observed the investigators. In addition, treatment with valproic acid in the early stages of Alzheimer’s disease alleviated memory deficits in the mice.

Education and occupation may reduce the severity and delay the clinical expression of Alzheimer’s disease, according to a study in the October 21 Neurology. The researchers assessed 242 patients with probable Alzheimer’s disease for the impact of education and occupation on brain glucose metabolism (rCMRglc) in patients with amnestic mild cognitive impairment (aMCI). A significant association was shown between higher education and occupation and lower rCMRglc in the posterior temporoparietal cortex and precuneus in those with probable Alzheimer’s disease and aMCI converters; no such correlation was found in aMCI nonconverters or the control group. “This study suggests that education and occupation may be proxies for brain functional reserve, reducing the severity and delaying the clinical expression of Alzheimer’s disease pathology,” the researchers concluded.

A high level of physical activity is associated with less severe first stroke and improved long-term outcome, according to a report in the October 21 Neurology. Researchers compiled data on 265 subjects (mean age, 68) who represented a subset of patients with first-ever stroke enrolled in the ExStroke Pilot Trial. Prestroke level of physical activity was measured retrospectively using the Physical Activity Scale for the Elderly questionnaire. Stroke severity was measured with the Scandinavian Stroke Scale, and long-term outcome was assessed after two years with the modified Rankin Scale. Patients in the lowest quartile of physical activity had the poorest outcome, as well as a more severe stroke. Higher physical activity was associated with a less severe stroke (odds ratio [OR], 2.54) and a decreased likelihood of poor long-term outcome (OR, 0.46).

Multiplex ligation-dependent probe amplification (MLPA) is an efficient and inexpensive tool for screening chromosomal abnormalities present in autism spectrum disorders, researchers reported in the October BMC Medical Genomics. A screening of 279 unrelated subjects showed duplications of the ­15q11-q13 region in two subjects, as well as duplications of the 22q11 region in two subjects. In an additional two patients, smaller de novo duplications were identified. Genes in these novel duplications included GABRB3 and ATP10A in one case and MKRN3, MAGEL2, and NDN in the other. These duplications likely exacerbate symptoms and/or increase liability for autism spectrum disorders. The researchers also found a partial duplication of the ASMT gene in 6% to 7% of cases, compared with 2% of controls, indicating that further study is needed to determine its potential impact on autism spectrum disorders. “MLPA proves to be an efficient method to screen for chromosomal abnormalities,” they stated.

Brain microbleeds are more prevalent in black patients than in white patients, according to a report in the October 7 Neurology. A total of 87 subjects (42 black, 45 white) with intracerebral hemorrhage (ICH) were analyzed. Black subjects were younger and had a greater rate of hypertension but did not have other vascular risk factors. Seventy-four percent of black patients had one or more microbleeds, compared with 42% of white patients. “The black population also tended to have a greater frequency of microbleeds in multiple territories than the white population (38% vs 22%),” the researchers observed. Race remained an independent predictor of microbleeds (odds ratio, 3.3), after adjusting for age, hypertension, and alcohol use. “Microbleeds may be an important emerging imaging biomarker with the potential to provide insights into ICH pathophysiology, prognosis, and disease progression,” the investigators concluded.

Patients with acute ischemic stroke who require aggressive measures to lower blood pressure should not be excluded from receiving intravenous t-PA therapy, according to a study in the September Archives of Neurology. Medical records of 178 patients with acute ischemic stroke who were treated with t-PA therapy were reviewed. Fifty patients required blood pressure–lowering treatment before receiving t-PA therapy; of these, 24 patients received nicardipine as first-line therapy or after receiving labetalol. There were no significant differences in adverse events between those treated with nicardipine or labetalol and those who did not receive blood pressure–lowering treatment. “Data suggest that patients with acute ischemic stroke requiring aggressive treatment to lower blood pressure should not be excluded from receiving t-PA therapy,” the authors concluded, noting that a prospective study is needed.

Carotid artery stenting is as efficacious as endarterectomy for the prevention of recurrent ipsilateral ischemic stroke, but safety concerns during the 30-day period following surgery need to be addressed, according to two studies in the October Lancet Neurology. In the Stent-Protected Angioplasty versus Carotid Endarterectomy study, patients underwent either carotid angioplasty with stenting (n = 613) or carotid endarterectomy (n = 601). After two years, the rate of recurrent ipsilateral ischemic stroke was similar in both treatment groups. In the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis trial, researchers compared outcome after stenting with outcome after endarterectomy after four years in 527 subjects who had carotid stenosis of at least 60% that had recently become symptomatic. The probability of periprocedural stroke or death and nonprocedural ipsilateral stroke was higher in those who received stenting than in those who received endarterectomy (11.1% vs 6.2%, respectively; hazard ratio, 1.97). The differences were attributed to “the higher periprocedural risk of stenting compared with endarterectomy,” said the researchers. After the periprocedural period, however, risks for ipsilateral stroke were similar in both treatment groups.

Fetal aneuploidy can be detected using a noninvasive maternal blood test, according to a study in the October 21 Proceedings of the National Academy of Sciences. Researchers used high-throughput shotgun technology to sequence cell-free DNA from the plasma of pregnant women, obtaining an average of five million sequence tags per patient sample. “The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy,” the investigators stated. Nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edwards syndrome), and one case of trisomy 13 (Patau syndrome) were observed among 12 women with aneuploid pregnancies and six women with normal pregnancies. Trisomy was detected as early as the 14th week of gestation. “Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA,” the study authors added, “and we found evidence that this DNA is enriched for sequences from nucleosomes.”

The FDA has approved two new dosage strengths for Stalevo (carbidopa, levodopa, and entacapone) tablets: 75 (18.75 mg of carbidopa, 75 mg of levodopa, and 200 mg entacapone) and 125 (31.25 mg of carbidopa, 125 mg of levodopa, and 200 mg of entacapone). The new dosage strengths are in addition to the already existing Stalevo 50, 100, 150, and 200 tablets. Stalevo is indicated for patients with Parkinson’s disease who experience end-of-dose “wearing off.” It combines levodopa with the enzyme inhibitors carbidopa and entacapone to provide greater and more sustained levels of levodopa in the blood and improve bodily movement control. The most common side effects include dyskinesia, hypokinesia, hyperkinesia, nausea, diarrhea, discoloration of urine, sweat, and/or saliva, abdominal pain, dizziness, constipation, fatigue, pain, and hallucinations. Stalevo was originally approved by the FDA in June 2003 and is marketed by Novartis Pharmaceuticals Corporation in East Hanover, New Jersey.

Vitamin D deficiency may have a role in Parkinson’s disease, reported researchers in the October Archives of Neurology. Patients with Parkinson’s disease were matched by age to healthy controls and patients with Alzheimer’s disease. More patients with Parkinson’s disease (55%) had insufficient vitamin D, compared with controls (36%) and patients with Alzheimer’s disease (41%). The Parkinson’s disease subjects also had significantly lower mean plasma 25-hydroxyvitamin D concentration than the Alzheimer’s disease and control cohorts (31.9 vs 34.8 and 37.0 ng/mL, respectively). “Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of Parkinson’s disease,” suggested the investigators.

Treatment with valproic acid was associated with improved memory and reduced brain lesions in a mouse model, reported researchers in the October 27 online Journal of Experimental Medicine. Valproic acid decreased β-amyloid protein production by inhibiting glycogen synthase kinase 3β–mediated γ-secretase cleavage of β-amyloid precursor protein in vitro and in vivo. “Valproic acid treatment significantly reduced neuritic plaque formation and improved memory deficits in transgenic Alzheimer’s disease model mice,” observed the investigators. In addition, treatment with valproic acid in the early stages of Alzheimer’s disease alleviated memory deficits in the mice.

Education and occupation may reduce the severity and delay the clinical expression of Alzheimer’s disease, according to a study in the October 21 Neurology. The researchers assessed 242 patients with probable Alzheimer’s disease for the impact of education and occupation on brain glucose metabolism (rCMRglc) in patients with amnestic mild cognitive impairment (aMCI). A significant association was shown between higher education and occupation and lower rCMRglc in the posterior temporoparietal cortex and precuneus in those with probable Alzheimer’s disease and aMCI converters; no such correlation was found in aMCI nonconverters or the control group. “This study suggests that education and occupation may be proxies for brain functional reserve, reducing the severity and delaying the clinical expression of Alzheimer’s disease pathology,” the researchers concluded.

A high level of physical activity is associated with less severe first stroke and improved long-term outcome, according to a report in the October 21 Neurology. Researchers compiled data on 265 subjects (mean age, 68) who represented a subset of patients with first-ever stroke enrolled in the ExStroke Pilot Trial. Prestroke level of physical activity was measured retrospectively using the Physical Activity Scale for the Elderly questionnaire. Stroke severity was measured with the Scandinavian Stroke Scale, and long-term outcome was assessed after two years with the modified Rankin Scale. Patients in the lowest quartile of physical activity had the poorest outcome, as well as a more severe stroke. Higher physical activity was associated with a less severe stroke (odds ratio [OR], 2.54) and a decreased likelihood of poor long-term outcome (OR, 0.46).

Multiplex ligation-dependent probe amplification (MLPA) is an efficient and inexpensive tool for screening chromosomal abnormalities present in autism spectrum disorders, researchers reported in the October BMC Medical Genomics. A screening of 279 unrelated subjects showed duplications of the ­15q11-q13 region in two subjects, as well as duplications of the 22q11 region in two subjects. In an additional two patients, smaller de novo duplications were identified. Genes in these novel duplications included GABRB3 and ATP10A in one case and MKRN3, MAGEL2, and NDN in the other. These duplications likely exacerbate symptoms and/or increase liability for autism spectrum disorders. The researchers also found a partial duplication of the ASMT gene in 6% to 7% of cases, compared with 2% of controls, indicating that further study is needed to determine its potential impact on autism spectrum disorders. “MLPA proves to be an efficient method to screen for chromosomal abnormalities,” they stated.

Brain microbleeds are more prevalent in black patients than in white patients, according to a report in the October 7 Neurology. A total of 87 subjects (42 black, 45 white) with intracerebral hemorrhage (ICH) were analyzed. Black subjects were younger and had a greater rate of hypertension but did not have other vascular risk factors. Seventy-four percent of black patients had one or more microbleeds, compared with 42% of white patients. “The black population also tended to have a greater frequency of microbleeds in multiple territories than the white population (38% vs 22%),” the researchers observed. Race remained an independent predictor of microbleeds (odds ratio, 3.3), after adjusting for age, hypertension, and alcohol use. “Microbleeds may be an important emerging imaging biomarker with the potential to provide insights into ICH pathophysiology, prognosis, and disease progression,” the investigators concluded.

Patients with acute ischemic stroke who require aggressive measures to lower blood pressure should not be excluded from receiving intravenous t-PA therapy, according to a study in the September Archives of Neurology. Medical records of 178 patients with acute ischemic stroke who were treated with t-PA therapy were reviewed. Fifty patients required blood pressure–lowering treatment before receiving t-PA therapy; of these, 24 patients received nicardipine as first-line therapy or after receiving labetalol. There were no significant differences in adverse events between those treated with nicardipine or labetalol and those who did not receive blood pressure–lowering treatment. “Data suggest that patients with acute ischemic stroke requiring aggressive treatment to lower blood pressure should not be excluded from receiving t-PA therapy,” the authors concluded, noting that a prospective study is needed.