News Roundup: New and Noteworthy Information

Low levels of vitamin B12 may cause brain atrophy and, subsequently, cognitive impairment in the elderly, according to the a study in the September 9 Neurology. The prospective five-year study included 107 community-dwelling volunteers ages 61 to 87 who did not have cognitive impairment at baseline. Patients with lower vitamin B12 and holotranscobalamin (holoTC) levels and higher plasma total homocysteine (tHcy) and methylmalonic acid levels at baseline had a greater decrease in brain volume. Associations between vitamin B12 and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, apolipo­protein E ε4 status, tHcy, and serum folate. The increased rate of brain volume loss was associated with the bottom tertile of vitamin B12 (Heavy alcoholic consumption is associated with increased mortality from total stroke and total cardiovascular disease for men and with increased mortality from coronary heart disease for women; however, light to moderate drinking may be associated with reduced mortality from cardiovascular disease for both sexes, according to a report in the November Stroke. Of the 34,776 men and 48,906 women from Japan who completed a self-administered questionnaire, 1,628 died from stroke and 736 died from coronary heart disease in the 14.2-year follow-up period. Among men, heavy drinking (≥ 46 g of ethanol per day) was associated with increased total mortality (hazard ratio [HR], 1.48) and mortality from hemorrhagic and ischemic strokes (HRs, 1.67 and 1.35, respectively). Light to moderate drinking was associated with reduced mortality from total cardiovascular disease (HR, 0.88) in this group, compared with not drinking. Women who drank heavily had increased mortality from coronary heart disease (HR, 4.10), while those who drank moderate amounts of alcohol (0.1 to 22.9 g of ethanol/day) had a reduced mortality from total cardiovascular disease (HR, 0.75), compared with nondrinkers.
The FDA has approved Xenazine (tetrabenazine) for the treatment of chorea associated with Huntington’s disease. Tetrabenazine is the first and only FDA-approved treatment for any symptom of Huntington’s disease and is expected to be available later this year. The approval was based on a double-blind placebo-controlled study that found that tetrabenazine significantly reduced patients’ chorea burden, improved global outcome scores, and was generally safe and well tolerated. Side effects included depression and suicidal thoughts and actions. Other common side effects included insomnia, drowsiness, restlessness, and nausea. The drug will be marketed under the Risk Evaluation and Mitigation Strategy, which includes educational materials to help decrease these risks. Xenazine is manufactured by Prestwick Pharmaceuticals.
Migraineurs do not have an increased risk for atherosclerosis but may have a higher risk for venous thromboembolism, reported researchers in the September 16 Neurology. A total of 574 participants ages 55 to 94 underwent neurologic and laboratory examinations. “Prevalence, severity, and five-year progression of carotid and femoral atherosclerosis did not differ significantly between migraineurs with and without aura and nonmigraineurs,” the investigators stated. There was also a tendency for atherosclerosis to be less pronounced and for the intima-media thickness to be lower among patients with migraine. However, migraineurs had a significantly enhanced risk of venous thromboembolism (18.9% vs 7.6% in nonmigraineurs), after adjustment for age and gender.
Keppra XR (levetiracetam extended-release tablets) has been approved by the FDA as an add-on to other antiepileptic treatments for patients 16 and older with partial-onset seizures. “We found in the clinical trial that Keppra XR provided significant partial-onset seizure control in once-daily dosing when added to other antiepileptic drugs and that it was well tolerated,” said lead investigator Jukka Peltola, MD.  The most common adverse reactions were somnolence and irritability. Adverse reactions to the extended-release form of levetiracetam are expected to be similar to those seen in patients taking the immediate-release form. Levetiracetam extended-release should be gradually withdrawn to minimize the potential for increased seizure frequency. For patients with end-stage renal disease who are on dialysis, the immediate-release form of levetiracetam is recommended over the extended-release form. Keppra XR is marketed by UCB.
Warfarin use is associated with larger initial intracerebral hemorrhage (ICH) volume and therefore greater mortality risk, according to a retrospective study in the September 30 Neurology. ICH volumes of hospitalized patients in the Cincinnati region throughout 2005 were measured using the abc/2 method. Univariable analyses and a multivariable generalized linear model were used to determine the influence of the international normalized ratio (INR) on ICH, after adjusting for age, race, gender, antiplatelet use, hemorrhage location, and time from stroke onset to scan. Of 258 patients, 51 were taking warfarin. “In univariable comparison, when INR was stratified, there was a trend toward a difference in hematoma volume by INR category,” the researchers said. “This effect was only observed for INR values greater than 3.0.” These findings may partially account for the higher mortality rate in this group.
Elevated levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM-2) in CSF may inhibit anti-inflammatory function of membrane-bound receptor cells and promote phagocytosis in microglial cells, according to a study in the September 12 online Brain. These findings suggest that sTREM-2 may be a possible target for future multiple sclerosis (MS) therapies. sTREM-2 levels were compared among subjects with various forms of MS and other inflammatory neurologic diseases, as well as noninflammatory neurologic diseases. Although levels of sTREM-2 in the bloodstream did not differ among groups, higher levels were found in the CSF of patients with relapsing-remitting MS, primary-progressive MS, and other inflammatory neurologic diseases.
Pain is a nonmotor feature of Parkinson’s disease that begins with the onset of the disease, according to a report in the September Archives of Neurology. A total of 402 patients with Parkinson’s disease were compared with 317 age-matched controls using logistic regression models that took into account the type of pain, time between pain and onset of Parkinson’s disease, and possible confounders. Overall pain frequency was substantially greater for those with Parkinson’s disease than for controls (69.9% vs 62.8%). Patients with Parkinson’s disease also had a higher frequency of cramping and central neuropathic pain. Nondystonic pain frequency was similar between both groups. “Nevertheless, we observed a significant association between Parkinson’s disease and nondystonic pain, beginning after the onset of parkinsonian symptoms,” the researchers stated. Approximately one-quarter of the subjects reported onset of pain before beginning antiparkinsonian therapy.
Intravenous alteplase treatment for acute is­chemic stroke is safe and effective up to 4.5 hours after onset, according to a study in the September 25 New England Journal of Medicine. A total of 821 patients were randomly assigned to an alteplase group (418) or a placebo group (403) in a double-blind study. The alteplase group was treated a median of three hours and 59 minutes after stroke onset. Disability at 90 days was determined as the primary end point. Subjects treated with alteplase had a favorable outcome of 0 or 1 on the modified Rankin scale, compared with the placebo group (52.4% vs 45.2%) and also faired better in global analysis measured by neurologic and disability scores. Other differences, including mortality, were not significant between groups.
The ketogenic diet should be the first-line therapy for epileptic infants, as it causes fewer side effects and relapses than adrenocorticotropic hormone (ACTH), according to a report in the September Epilepsia. A retrospective chart review of infants started on the ketogenic diet or high-dose ACTH was conducted. Researchers found that eight of 13 infants treated with the ketogenic diet were spasm-free within one month, compared with 18 of 20 treated with ACTH. EEG normalization was achieved within two to five months in the eight infants who became spasm-free with the ketogenic diet. Of the five patients in whom the ketogenic diet was unsuccessful, four became spasm-free after ACTH or topiramate was administered. The ketogenic diet was associated with fewer side effects and relapses than ACTH, the researchers concluded.
Microvascular changes caused by vitamin B deficiency may lead to hyperhomocysteinemia and vascular cognitive impairment, according to a study in the August 26 Proceedings of the National Academy of Sciences. Researchers fed male mice a vitamin B–deficient diet for 10 weeks. This induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. “Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies, and with plasma total homocysteine,” the investigators reported. A methionine-rich diet was associated with similar but less pronounced effects. The research suggests that “cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration,” the study authors noted. “Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline.”

Low levels of vitamin B12 may cause brain atrophy and, subsequently, cognitive impairment in the elderly, according to the a study in the September 9 Neurology. The prospective five-year study included 107 community-dwelling volunteers ages 61 to 87 who did not have cognitive impairment at baseline. Patients with lower vitamin B12 and holotranscobalamin (holoTC) levels and higher plasma total homocysteine (tHcy) and methylmalonic acid levels at baseline had a greater decrease in brain volume. Associations between vitamin B12 and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, apolipo­protein E ε4 status, tHcy, and serum folate. The increased rate of brain volume loss was associated with the bottom tertile of vitamin B12 (Heavy alcoholic consumption is associated with increased mortality from total stroke and total cardiovascular disease for men and with increased mortality from coronary heart disease for women; however, light to moderate drinking may be associated with reduced mortality from cardiovascular disease for both sexes, according to a report in the November Stroke. Of the 34,776 men and 48,906 women from Japan who completed a self-administered questionnaire, 1,628 died from stroke and 736 died from coronary heart disease in the 14.2-year follow-up period. Among men, heavy drinking (≥ 46 g of ethanol per day) was associated with increased total mortality (hazard ratio [HR], 1.48) and mortality from hemorrhagic and ischemic strokes (HRs, 1.67 and 1.35, respectively). Light to moderate drinking was associated with reduced mortality from total cardiovascular disease (HR, 0.88) in this group, compared with not drinking. Women who drank heavily had increased mortality from coronary heart disease (HR, 4.10), while those who drank moderate amounts of alcohol (0.1 to 22.9 g of ethanol/day) had a reduced mortality from total cardiovascular disease (HR, 0.75), compared with nondrinkers.
The FDA has approved Xenazine (tetrabenazine) for the treatment of chorea associated with Huntington’s disease. Tetrabenazine is the first and only FDA-approved treatment for any symptom of Huntington’s disease and is expected to be available later this year. The approval was based on a double-blind placebo-controlled study that found that tetrabenazine significantly reduced patients’ chorea burden, improved global outcome scores, and was generally safe and well tolerated. Side effects included depression and suicidal thoughts and actions. Other common side effects included insomnia, drowsiness, restlessness, and nausea. The drug will be marketed under the Risk Evaluation and Mitigation Strategy, which includes educational materials to help decrease these risks. Xenazine is manufactured by Prestwick Pharmaceuticals.
Migraineurs do not have an increased risk for atherosclerosis but may have a higher risk for venous thromboembolism, reported researchers in the September 16 Neurology. A total of 574 participants ages 55 to 94 underwent neurologic and laboratory examinations. “Prevalence, severity, and five-year progression of carotid and femoral atherosclerosis did not differ significantly between migraineurs with and without aura and nonmigraineurs,” the investigators stated. There was also a tendency for atherosclerosis to be less pronounced and for the intima-media thickness to be lower among patients with migraine. However, migraineurs had a significantly enhanced risk of venous thromboembolism (18.9% vs 7.6% in nonmigraineurs), after adjustment for age and gender.
Keppra XR (levetiracetam extended-release tablets) has been approved by the FDA as an add-on to other antiepileptic treatments for patients 16 and older with partial-onset seizures. “We found in the clinical trial that Keppra XR provided significant partial-onset seizure control in once-daily dosing when added to other antiepileptic drugs and that it was well tolerated,” said lead investigator Jukka Peltola, MD.  The most common adverse reactions were somnolence and irritability. Adverse reactions to the extended-release form of levetiracetam are expected to be similar to those seen in patients taking the immediate-release form. Levetiracetam extended-release should be gradually withdrawn to minimize the potential for increased seizure frequency. For patients with end-stage renal disease who are on dialysis, the immediate-release form of levetiracetam is recommended over the extended-release form. Keppra XR is marketed by UCB.
Warfarin use is associated with larger initial intracerebral hemorrhage (ICH) volume and therefore greater mortality risk, according to a retrospective study in the September 30 Neurology. ICH volumes of hospitalized patients in the Cincinnati region throughout 2005 were measured using the abc/2 method. Univariable analyses and a multivariable generalized linear model were used to determine the influence of the international normalized ratio (INR) on ICH, after adjusting for age, race, gender, antiplatelet use, hemorrhage location, and time from stroke onset to scan. Of 258 patients, 51 were taking warfarin. “In univariable comparison, when INR was stratified, there was a trend toward a difference in hematoma volume by INR category,” the researchers said. “This effect was only observed for INR values greater than 3.0.” These findings may partially account for the higher mortality rate in this group.
Elevated levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM-2) in CSF may inhibit anti-inflammatory function of membrane-bound receptor cells and promote phagocytosis in microglial cells, according to a study in the September 12 online Brain. These findings suggest that sTREM-2 may be a possible target for future multiple sclerosis (MS) therapies. sTREM-2 levels were compared among subjects with various forms of MS and other inflammatory neurologic diseases, as well as noninflammatory neurologic diseases. Although levels of sTREM-2 in the bloodstream did not differ among groups, higher levels were found in the CSF of patients with relapsing-remitting MS, primary-progressive MS, and other inflammatory neurologic diseases.
Pain is a nonmotor feature of Parkinson’s disease that begins with the onset of the disease, according to a report in the September Archives of Neurology. A total of 402 patients with Parkinson’s disease were compared with 317 age-matched controls using logistic regression models that took into account the type of pain, time between pain and onset of Parkinson’s disease, and possible confounders. Overall pain frequency was substantially greater for those with Parkinson’s disease than for controls (69.9% vs 62.8%). Patients with Parkinson’s disease also had a higher frequency of cramping and central neuropathic pain. Nondystonic pain frequency was similar between both groups. “Nevertheless, we observed a significant association between Parkinson’s disease and nondystonic pain, beginning after the onset of parkinsonian symptoms,” the researchers stated. Approximately one-quarter of the subjects reported onset of pain before beginning antiparkinsonian therapy.
Intravenous alteplase treatment for acute is­chemic stroke is safe and effective up to 4.5 hours after onset, according to a study in the September 25 New England Journal of Medicine. A total of 821 patients were randomly assigned to an alteplase group (418) or a placebo group (403) in a double-blind study. The alteplase group was treated a median of three hours and 59 minutes after stroke onset. Disability at 90 days was determined as the primary end point. Subjects treated with alteplase had a favorable outcome of 0 or 1 on the modified Rankin scale, compared with the placebo group (52.4% vs 45.2%) and also faired better in global analysis measured by neurologic and disability scores. Other differences, including mortality, were not significant between groups.
The ketogenic diet should be the first-line therapy for epileptic infants, as it causes fewer side effects and relapses than adrenocorticotropic hormone (ACTH), according to a report in the September Epilepsia. A retrospective chart review of infants started on the ketogenic diet or high-dose ACTH was conducted. Researchers found that eight of 13 infants treated with the ketogenic diet were spasm-free within one month, compared with 18 of 20 treated with ACTH. EEG normalization was achieved within two to five months in the eight infants who became spasm-free with the ketogenic diet. Of the five patients in whom the ketogenic diet was unsuccessful, four became spasm-free after ACTH or topiramate was administered. The ketogenic diet was associated with fewer side effects and relapses than ACTH, the researchers concluded.
Microvascular changes caused by vitamin B deficiency may lead to hyperhomocysteinemia and vascular cognitive impairment, according to a study in the August 26 Proceedings of the National Academy of Sciences. Researchers fed male mice a vitamin B–deficient diet for 10 weeks. This induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. “Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies, and with plasma total homocysteine,” the investigators reported. A methionine-rich diet was associated with similar but less pronounced effects. The research suggests that “cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration,” the study authors noted. “Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline.”

Low levels of vitamin B12 may cause brain atrophy and, subsequently, cognitive impairment in the elderly, according to the a study in the September 9 Neurology. The prospective five-year study included 107 community-dwelling volunteers ages 61 to 87 who did not have cognitive impairment at baseline. Patients with lower vitamin B12 and holotranscobalamin (holoTC) levels and higher plasma total homocysteine (tHcy) and methylmalonic acid levels at baseline had a greater decrease in brain volume. Associations between vitamin B12 and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, apolipo­protein E ε4 status, tHcy, and serum folate. The increased rate of brain volume loss was associated with the bottom tertile of vitamin B12 (Heavy alcoholic consumption is associated with increased mortality from total stroke and total cardiovascular disease for men and with increased mortality from coronary heart disease for women; however, light to moderate drinking may be associated with reduced mortality from cardiovascular disease for both sexes, according to a report in the November Stroke. Of the 34,776 men and 48,906 women from Japan who completed a self-administered questionnaire, 1,628 died from stroke and 736 died from coronary heart disease in the 14.2-year follow-up period. Among men, heavy drinking (≥ 46 g of ethanol per day) was associated with increased total mortality (hazard ratio [HR], 1.48) and mortality from hemorrhagic and ischemic strokes (HRs, 1.67 and 1.35, respectively). Light to moderate drinking was associated with reduced mortality from total cardiovascular disease (HR, 0.88) in this group, compared with not drinking. Women who drank heavily had increased mortality from coronary heart disease (HR, 4.10), while those who drank moderate amounts of alcohol (0.1 to 22.9 g of ethanol/day) had a reduced mortality from total cardiovascular disease (HR, 0.75), compared with nondrinkers.
The FDA has approved Xenazine (tetrabenazine) for the treatment of chorea associated with Huntington’s disease. Tetrabenazine is the first and only FDA-approved treatment for any symptom of Huntington’s disease and is expected to be available later this year. The approval was based on a double-blind placebo-controlled study that found that tetrabenazine significantly reduced patients’ chorea burden, improved global outcome scores, and was generally safe and well tolerated. Side effects included depression and suicidal thoughts and actions. Other common side effects included insomnia, drowsiness, restlessness, and nausea. The drug will be marketed under the Risk Evaluation and Mitigation Strategy, which includes educational materials to help decrease these risks. Xenazine is manufactured by Prestwick Pharmaceuticals.
Migraineurs do not have an increased risk for atherosclerosis but may have a higher risk for venous thromboembolism, reported researchers in the September 16 Neurology. A total of 574 participants ages 55 to 94 underwent neurologic and laboratory examinations. “Prevalence, severity, and five-year progression of carotid and femoral atherosclerosis did not differ significantly between migraineurs with and without aura and nonmigraineurs,” the investigators stated. There was also a tendency for atherosclerosis to be less pronounced and for the intima-media thickness to be lower among patients with migraine. However, migraineurs had a significantly enhanced risk of venous thromboembolism (18.9% vs 7.6% in nonmigraineurs), after adjustment for age and gender.
Keppra XR (levetiracetam extended-release tablets) has been approved by the FDA as an add-on to other antiepileptic treatments for patients 16 and older with partial-onset seizures. “We found in the clinical trial that Keppra XR provided significant partial-onset seizure control in once-daily dosing when added to other antiepileptic drugs and that it was well tolerated,” said lead investigator Jukka Peltola, MD.  The most common adverse reactions were somnolence and irritability. Adverse reactions to the extended-release form of levetiracetam are expected to be similar to those seen in patients taking the immediate-release form. Levetiracetam extended-release should be gradually withdrawn to minimize the potential for increased seizure frequency. For patients with end-stage renal disease who are on dialysis, the immediate-release form of levetiracetam is recommended over the extended-release form. Keppra XR is marketed by UCB.
Warfarin use is associated with larger initial intracerebral hemorrhage (ICH) volume and therefore greater mortality risk, according to a retrospective study in the September 30 Neurology. ICH volumes of hospitalized patients in the Cincinnati region throughout 2005 were measured using the abc/2 method. Univariable analyses and a multivariable generalized linear model were used to determine the influence of the international normalized ratio (INR) on ICH, after adjusting for age, race, gender, antiplatelet use, hemorrhage location, and time from stroke onset to scan. Of 258 patients, 51 were taking warfarin. “In univariable comparison, when INR was stratified, there was a trend toward a difference in hematoma volume by INR category,” the researchers said. “This effect was only observed for INR values greater than 3.0.” These findings may partially account for the higher mortality rate in this group.
Elevated levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM-2) in CSF may inhibit anti-inflammatory function of membrane-bound receptor cells and promote phagocytosis in microglial cells, according to a study in the September 12 online Brain. These findings suggest that sTREM-2 may be a possible target for future multiple sclerosis (MS) therapies. sTREM-2 levels were compared among subjects with various forms of MS and other inflammatory neurologic diseases, as well as noninflammatory neurologic diseases. Although levels of sTREM-2 in the bloodstream did not differ among groups, higher levels were found in the CSF of patients with relapsing-remitting MS, primary-progressive MS, and other inflammatory neurologic diseases.
Pain is a nonmotor feature of Parkinson’s disease that begins with the onset of the disease, according to a report in the September Archives of Neurology. A total of 402 patients with Parkinson’s disease were compared with 317 age-matched controls using logistic regression models that took into account the type of pain, time between pain and onset of Parkinson’s disease, and possible confounders. Overall pain frequency was substantially greater for those with Parkinson’s disease than for controls (69.9% vs 62.8%). Patients with Parkinson’s disease also had a higher frequency of cramping and central neuropathic pain. Nondystonic pain frequency was similar between both groups. “Nevertheless, we observed a significant association between Parkinson’s disease and nondystonic pain, beginning after the onset of parkinsonian symptoms,” the researchers stated. Approximately one-quarter of the subjects reported onset of pain before beginning antiparkinsonian therapy.
Intravenous alteplase treatment for acute is­chemic stroke is safe and effective up to 4.5 hours after onset, according to a study in the September 25 New England Journal of Medicine. A total of 821 patients were randomly assigned to an alteplase group (418) or a placebo group (403) in a double-blind study. The alteplase group was treated a median of three hours and 59 minutes after stroke onset. Disability at 90 days was determined as the primary end point. Subjects treated with alteplase had a favorable outcome of 0 or 1 on the modified Rankin scale, compared with the placebo group (52.4% vs 45.2%) and also faired better in global analysis measured by neurologic and disability scores. Other differences, including mortality, were not significant between groups.
The ketogenic diet should be the first-line therapy for epileptic infants, as it causes fewer side effects and relapses than adrenocorticotropic hormone (ACTH), according to a report in the September Epilepsia. A retrospective chart review of infants started on the ketogenic diet or high-dose ACTH was conducted. Researchers found that eight of 13 infants treated with the ketogenic diet were spasm-free within one month, compared with 18 of 20 treated with ACTH. EEG normalization was achieved within two to five months in the eight infants who became spasm-free with the ketogenic diet. Of the five patients in whom the ketogenic diet was unsuccessful, four became spasm-free after ACTH or topiramate was administered. The ketogenic diet was associated with fewer side effects and relapses than ACTH, the researchers concluded.
Microvascular changes caused by vitamin B deficiency may lead to hyperhomocysteinemia and vascular cognitive impairment, according to a study in the August 26 Proceedings of the National Academy of Sciences. Researchers fed male mice a vitamin B–deficient diet for 10 weeks. This induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. “Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies, and with plasma total homocysteine,” the investigators reported. A methionine-rich diet was associated with similar but less pronounced effects. The research suggests that “cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration,” the study authors noted. “Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline.”