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American Neurological Association (ANA): Annual Meeting 2016
Blood pressure changes and persistent hypertension elevate dementia risk
BALTIMORE – The impact of blood pressure on the risk of dementia in late life follows a U-shaped curve in which elevated mid-life and late-life blood pressure, as well as late-life decline in blood pressure, all independently raise the risk of dementia, according to findings from a longitudinal study of the Framingham Offspring cohort of the Framingham Heart Study.
The findings highlight the benefits of establishing and maintaining lower blood pressure in midlife in preventing or lowering the risk of dementia, Emer McGrath, MD, said at the annual meeting of the American Neurological Association.
The researchers explored the issue using data from the Framingham Offspring cohort of the Framingham Heart Study. The cohort comprises 5,124 children, and spouses of children, of the original Framingham cohort. They have been examined clinically at regular intervals since 1971. The present study focused on 1,440 individuals who had five consecutive examinations during a 15-year period anytime between 1983 and 2001 and who had not been diagnosed with dementia at the time of the final blood pressure determination.
The 1,440 participants had a mean age of 69 years at their fifth examination. Just over half were female, 20% had been diagnosed with cardiovascular disease, and slightly less than 20% had been diagnosed with diabetes. Half were using antihypertensive medications.
During a mean 8-year follow-up period, 107 individuals developed dementia. Dementia was independently associated with midlife hypertension (140/90 mm Hg or higher), with a stronger association for systolic hypertension (hazard ratio, 1.57; 95% confidence interval, 1.05-2.35). Persistence of hypertension into late life, particularly systolic hypertension (HR, 1.96; 95% CI, 1.25-3.09), was another independent risk factor for dementia.
Among individuals who did not have hypertension at midlife, a decline in systolic blood pressure to less than 100/70 mm Hg in the ensuing years increased the risk of dementia (HR, 1.63; 95% CI, 1.08-2.46).
According to the researchers, the findings support the hypothesis of the U-shaped relationship between blood pressure and dementia. “Our data also highlight the potential sustained cognitive benefits of lower midlife blood pressure,” Dr. McGrath said.
The study was funded by the Framingham Heart Study, the National Institute on Aging, and the National Institute for Neurological Diseases and Stroke. Dr. McGrath had no disclosures.
BALTIMORE – The impact of blood pressure on the risk of dementia in late life follows a U-shaped curve in which elevated mid-life and late-life blood pressure, as well as late-life decline in blood pressure, all independently raise the risk of dementia, according to findings from a longitudinal study of the Framingham Offspring cohort of the Framingham Heart Study.
The findings highlight the benefits of establishing and maintaining lower blood pressure in midlife in preventing or lowering the risk of dementia, Emer McGrath, MD, said at the annual meeting of the American Neurological Association.
The researchers explored the issue using data from the Framingham Offspring cohort of the Framingham Heart Study. The cohort comprises 5,124 children, and spouses of children, of the original Framingham cohort. They have been examined clinically at regular intervals since 1971. The present study focused on 1,440 individuals who had five consecutive examinations during a 15-year period anytime between 1983 and 2001 and who had not been diagnosed with dementia at the time of the final blood pressure determination.
The 1,440 participants had a mean age of 69 years at their fifth examination. Just over half were female, 20% had been diagnosed with cardiovascular disease, and slightly less than 20% had been diagnosed with diabetes. Half were using antihypertensive medications.
During a mean 8-year follow-up period, 107 individuals developed dementia. Dementia was independently associated with midlife hypertension (140/90 mm Hg or higher), with a stronger association for systolic hypertension (hazard ratio, 1.57; 95% confidence interval, 1.05-2.35). Persistence of hypertension into late life, particularly systolic hypertension (HR, 1.96; 95% CI, 1.25-3.09), was another independent risk factor for dementia.
Among individuals who did not have hypertension at midlife, a decline in systolic blood pressure to less than 100/70 mm Hg in the ensuing years increased the risk of dementia (HR, 1.63; 95% CI, 1.08-2.46).
According to the researchers, the findings support the hypothesis of the U-shaped relationship between blood pressure and dementia. “Our data also highlight the potential sustained cognitive benefits of lower midlife blood pressure,” Dr. McGrath said.
The study was funded by the Framingham Heart Study, the National Institute on Aging, and the National Institute for Neurological Diseases and Stroke. Dr. McGrath had no disclosures.
BALTIMORE – The impact of blood pressure on the risk of dementia in late life follows a U-shaped curve in which elevated mid-life and late-life blood pressure, as well as late-life decline in blood pressure, all independently raise the risk of dementia, according to findings from a longitudinal study of the Framingham Offspring cohort of the Framingham Heart Study.
The findings highlight the benefits of establishing and maintaining lower blood pressure in midlife in preventing or lowering the risk of dementia, Emer McGrath, MD, said at the annual meeting of the American Neurological Association.
The researchers explored the issue using data from the Framingham Offspring cohort of the Framingham Heart Study. The cohort comprises 5,124 children, and spouses of children, of the original Framingham cohort. They have been examined clinically at regular intervals since 1971. The present study focused on 1,440 individuals who had five consecutive examinations during a 15-year period anytime between 1983 and 2001 and who had not been diagnosed with dementia at the time of the final blood pressure determination.
The 1,440 participants had a mean age of 69 years at their fifth examination. Just over half were female, 20% had been diagnosed with cardiovascular disease, and slightly less than 20% had been diagnosed with diabetes. Half were using antihypertensive medications.
During a mean 8-year follow-up period, 107 individuals developed dementia. Dementia was independently associated with midlife hypertension (140/90 mm Hg or higher), with a stronger association for systolic hypertension (hazard ratio, 1.57; 95% confidence interval, 1.05-2.35). Persistence of hypertension into late life, particularly systolic hypertension (HR, 1.96; 95% CI, 1.25-3.09), was another independent risk factor for dementia.
Among individuals who did not have hypertension at midlife, a decline in systolic blood pressure to less than 100/70 mm Hg in the ensuing years increased the risk of dementia (HR, 1.63; 95% CI, 1.08-2.46).
According to the researchers, the findings support the hypothesis of the U-shaped relationship between blood pressure and dementia. “Our data also highlight the potential sustained cognitive benefits of lower midlife blood pressure,” Dr. McGrath said.
The study was funded by the Framingham Heart Study, the National Institute on Aging, and the National Institute for Neurological Diseases and Stroke. Dr. McGrath had no disclosures.
AT ANA 2016
Key clinical point:
Major finding: Persistence of hypertension into late life, particularly systolic hypertension (HR, 1.96; 95% CI, 1.25-3.09), was another independent risk factor for dementia.
Data source: Offspring cohort of the Framingham Heart Study.
Disclosures: The study was funded by the Framingham Heart Study, the National Institute on Aging, and the National Institute for Neurological Diseases and Stroke. Dr. McGrath had no disclosures.
Deep brain stimulation for early Parkinson’s disease has long-term benefit
BALTIMORE – The use of subthalamic nucleus deep brain stimulation (DBS) along with optimal drug therapy in patients with early stage Parkinson’s disease produced clinically meaningful improvements in clinician-assessed motor control that lasted at least 5 years in a prospective pilot study.
If the findings bear out a phase III trial that has been approved, DBS may become a valuable method to achieve long-term improvement in motor skills in patients with Parkinson’s disease.
The pilot trial involved 30 patients with Parkinson’s disease, aged 50-75 years, and demonstrated the safety and benefit of DBS in conjunction with optimal drug therapy (ODT) – involving drugs such as carbidopa/levodopa, pramipexole, ropinirole, and selegiline – compared with ODT alone in improving motor scores of the patients through 2 years (Parkinsonism Relat Disord. 2014. 20[7]:731-7). The latest subanalysis of the trial data took a longer look, examining the effect of DBS through 5 years.
The subanalysis involved 28 patients; 14 in the DBS plus ODT group and 14 in the ODT-only group. Both groups were predominantly male and were similar in age at baseline (about 61 years). Motor control was assessed during the periods when DBS was applied and not applied by using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III (clinician assessed) and the Hoehn and Yahr scale.
Over the 5-year period, mean UPDRS motor scores progressively worsened for the ODT group but improved for patients receiving DBS. Patients who received DBS plus ODT had improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.
“These results demonstrate that subthalamic nucleus deep brain stimulation applied in early-stage Parkinson’s disease may provide long-term, clinically meaningful improvement in motor function over standard clinical therapy,” Dr. Hacker said.
The exact mechanism of DBS is still unknown. But, there is evidence that synaptic plasticity is involved. Dr. Hacker speculated that in early Parkinson’s, the DBS intervention comes at a time of relative neuronal stability, which is then maintained.
The results of the pilot trial led to Food and Drug Administration approval of a large-scale, multicenter clinical trial. All participants will be implanted with a DBS device and will receive ODT. Some of the subjects will be randomized to receive DBS during the first 2 years, along with ODT, with the remainder receiving ODT only. In the next 2 years, all subjects will receive DBS and ODT.
Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research. Dr. Hacker had no disclosures.
BALTIMORE – The use of subthalamic nucleus deep brain stimulation (DBS) along with optimal drug therapy in patients with early stage Parkinson’s disease produced clinically meaningful improvements in clinician-assessed motor control that lasted at least 5 years in a prospective pilot study.
If the findings bear out a phase III trial that has been approved, DBS may become a valuable method to achieve long-term improvement in motor skills in patients with Parkinson’s disease.
The pilot trial involved 30 patients with Parkinson’s disease, aged 50-75 years, and demonstrated the safety and benefit of DBS in conjunction with optimal drug therapy (ODT) – involving drugs such as carbidopa/levodopa, pramipexole, ropinirole, and selegiline – compared with ODT alone in improving motor scores of the patients through 2 years (Parkinsonism Relat Disord. 2014. 20[7]:731-7). The latest subanalysis of the trial data took a longer look, examining the effect of DBS through 5 years.
The subanalysis involved 28 patients; 14 in the DBS plus ODT group and 14 in the ODT-only group. Both groups were predominantly male and were similar in age at baseline (about 61 years). Motor control was assessed during the periods when DBS was applied and not applied by using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III (clinician assessed) and the Hoehn and Yahr scale.
Over the 5-year period, mean UPDRS motor scores progressively worsened for the ODT group but improved for patients receiving DBS. Patients who received DBS plus ODT had improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.
“These results demonstrate that subthalamic nucleus deep brain stimulation applied in early-stage Parkinson’s disease may provide long-term, clinically meaningful improvement in motor function over standard clinical therapy,” Dr. Hacker said.
The exact mechanism of DBS is still unknown. But, there is evidence that synaptic plasticity is involved. Dr. Hacker speculated that in early Parkinson’s, the DBS intervention comes at a time of relative neuronal stability, which is then maintained.
The results of the pilot trial led to Food and Drug Administration approval of a large-scale, multicenter clinical trial. All participants will be implanted with a DBS device and will receive ODT. Some of the subjects will be randomized to receive DBS during the first 2 years, along with ODT, with the remainder receiving ODT only. In the next 2 years, all subjects will receive DBS and ODT.
Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research. Dr. Hacker had no disclosures.
BALTIMORE – The use of subthalamic nucleus deep brain stimulation (DBS) along with optimal drug therapy in patients with early stage Parkinson’s disease produced clinically meaningful improvements in clinician-assessed motor control that lasted at least 5 years in a prospective pilot study.
If the findings bear out a phase III trial that has been approved, DBS may become a valuable method to achieve long-term improvement in motor skills in patients with Parkinson’s disease.
The pilot trial involved 30 patients with Parkinson’s disease, aged 50-75 years, and demonstrated the safety and benefit of DBS in conjunction with optimal drug therapy (ODT) – involving drugs such as carbidopa/levodopa, pramipexole, ropinirole, and selegiline – compared with ODT alone in improving motor scores of the patients through 2 years (Parkinsonism Relat Disord. 2014. 20[7]:731-7). The latest subanalysis of the trial data took a longer look, examining the effect of DBS through 5 years.
The subanalysis involved 28 patients; 14 in the DBS plus ODT group and 14 in the ODT-only group. Both groups were predominantly male and were similar in age at baseline (about 61 years). Motor control was assessed during the periods when DBS was applied and not applied by using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III (clinician assessed) and the Hoehn and Yahr scale.
Over the 5-year period, mean UPDRS motor scores progressively worsened for the ODT group but improved for patients receiving DBS. Patients who received DBS plus ODT had improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.
“These results demonstrate that subthalamic nucleus deep brain stimulation applied in early-stage Parkinson’s disease may provide long-term, clinically meaningful improvement in motor function over standard clinical therapy,” Dr. Hacker said.
The exact mechanism of DBS is still unknown. But, there is evidence that synaptic plasticity is involved. Dr. Hacker speculated that in early Parkinson’s, the DBS intervention comes at a time of relative neuronal stability, which is then maintained.
The results of the pilot trial led to Food and Drug Administration approval of a large-scale, multicenter clinical trial. All participants will be implanted with a DBS device and will receive ODT. Some of the subjects will be randomized to receive DBS during the first 2 years, along with ODT, with the remainder receiving ODT only. In the next 2 years, all subjects will receive DBS and ODT.
Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research. Dr. Hacker had no disclosures.
Key clinical point:
Major finding: Patients who received DBS plus ODT had UPDRS motor score improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.
Data source: Secondary analysis of a pilot, prospective, randomized, controlled, single-blind clinical trial involving 30 patients with early Parkinson’s disease.
Disclosures: Dr. Hacker had no disclosures. Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research.
New trials address unresolved issues in endovascular therapy for acute ischemic stroke
BALTIMORE – Endovascular therapy is a bedrock of acute ischemic stroke treatment, but some vexing issues remain unresolved, according to Joseph Broderick, MD, of the University of Cincinnati.
“We have learned a tremendous amount the last few years. We know that thrombectomy can work if initiated in patients within 6 hours of stroke onset with or without TPA [tissue plasminogen activator]. The question is what we don’t know,” Dr. Broderick said.
The good news is that clinical trials are underway or planned to address several of these issues, he said at the annual meeting of the American Neurological Association.
Mechanical thrombectomy beyond 6 hours
Whether the treatment window for thrombectomy can be safely extended in appropriately selected patients beyond 6 hours from onset is “one of the most important issues we face,” Dr. Broderick said.
Along with DEFUSE 3, the DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention (DAWN) trial will examine whether medical management that includes thrombectomy delivered up to 24 hours after AIS symptoms first appear will yield better clinical outcomes than medical management alone in appropriate patients.
The use of mechanical thrombectomy up to 12 hours after symptom development in AIS patients for whom intravenous TPA can’t be used or doesn’t work will be assessed in the Perfusion Imaging Selection of Ischemic Stroke Patients for Endovascular Therapy (POSITIVE) trial. The primary objective is to show less stroke-related disability and improved good functional outcomes, compared with those who receive best medical therapy.
The first Multicenter Randomized Clinical Trial of Endovascular Treatment in the Netherlands (MR CLEAN) trial, which used stent retrievers in almost all cases, demonstrated the benefit of endovascular therapy up to 6 hours after stroke onset in the proximal anterior circulation when used along with best medical therapy (N Engl J Med. 2015;372:11-20). The MR CLEAN LATE trial involving 500 patients will expand the time window up to 12 hours.
Triage of acute stroke patients
The triage of AIS patients before their arrival at the hospital also is an evolving emergency medical service issue. While the classic triage involving CT takes time, the use of scoring systems like the National Institutes of Health Stroke Scale and the Cincinnati Stroke Triage Assessment Tool, or telemedicine-based consultation, can be done faster and with less training.
Where the patient is taken first could be important. The RACECAT trial being conducted in the Catalan territory will compare transfer of acute stroke patients with suspected large-vessel occlusion to the closest local stroke center versus direct transfer to an endovascular stroke center.
Conscious sedation or general anesthesia
Some patients undergoing thrombectomy may be able to tolerate conscious sedation in place of general anesthesia. For these patients, cost-effectiveness becomes a dominant consideration. Several anesthesia trials are addressing the issue. The Sedation Versus Intubation for Endovascular Stroke Treatment (SIESTA) trial involving 150 German patients has been completed, but the findings have not been reported. The General or Local Anaesthesia in Intra-arterial Therapy (GOLIATH) trial is recruiting patients in the Netherlands, with a target enrollment of 128. Other trials are planned in China and Sweden, but recruitment has not started.
Thrombectomy alone
For patients with AIS caused by basilar artery occlusion, stroke specialists have wondered whether intra-arterial treatment, including thrombolysis and potentially thrombectomy, could be more effective than best medical therapy, including intravenous thrombolysis. The Basilar Artery International Cooperation Study (BASICS) in Europe and the BEST trial in China are two trials in the early stages of assessing this question.
A related issue is whether thrombectomy alone is better than intravenous TPA followed by thrombectomy. This issue is being addressed in another MR CLEAN trial that is designed to compare the two approaches in 500 patients randomized to one or the other treatment.
Other intravenous antithrombotic drugs
Another unresolved issue relates to the use of other antithrombotic medications delivered intravenously in combination with TPA. This could be the sole treatment strategy, or could be used in patients who also undergo endovascular thrombectomy. The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial will randomize patients to receive argatroban or eptifibatide along with TPA, or TPA alone, within 3 hours of stroke symptom onset. Endovascular therapy will be done as indicated.
Heparin use in endovascular therapy
The proper use of antithrombotics like heparin in patients treated with endovascular therapy is unclear. The MR CLEAN MED trial will assess the benefits of two doses of unfractionated heparin and aspirin alone or in combination in 1,500 patients with AIS who receive intra-arterial treatment for confirmed anterior circulation occlusion.
On the horizon
Whether neuroprotection can improve the outcome in patients who undergo embolectomy is unclear, and will be the subject of a trial in Canada that is not yet recruiting patients. Finally, the best way to manage blood pressure following embolectomy and reperfusion is also unclear.
Dr. Broderick had no relevant financial disclosures.
BALTIMORE – Endovascular therapy is a bedrock of acute ischemic stroke treatment, but some vexing issues remain unresolved, according to Joseph Broderick, MD, of the University of Cincinnati.
“We have learned a tremendous amount the last few years. We know that thrombectomy can work if initiated in patients within 6 hours of stroke onset with or without TPA [tissue plasminogen activator]. The question is what we don’t know,” Dr. Broderick said.
The good news is that clinical trials are underway or planned to address several of these issues, he said at the annual meeting of the American Neurological Association.
Mechanical thrombectomy beyond 6 hours
Whether the treatment window for thrombectomy can be safely extended in appropriately selected patients beyond 6 hours from onset is “one of the most important issues we face,” Dr. Broderick said.
Along with DEFUSE 3, the DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention (DAWN) trial will examine whether medical management that includes thrombectomy delivered up to 24 hours after AIS symptoms first appear will yield better clinical outcomes than medical management alone in appropriate patients.
The use of mechanical thrombectomy up to 12 hours after symptom development in AIS patients for whom intravenous TPA can’t be used or doesn’t work will be assessed in the Perfusion Imaging Selection of Ischemic Stroke Patients for Endovascular Therapy (POSITIVE) trial. The primary objective is to show less stroke-related disability and improved good functional outcomes, compared with those who receive best medical therapy.
The first Multicenter Randomized Clinical Trial of Endovascular Treatment in the Netherlands (MR CLEAN) trial, which used stent retrievers in almost all cases, demonstrated the benefit of endovascular therapy up to 6 hours after stroke onset in the proximal anterior circulation when used along with best medical therapy (N Engl J Med. 2015;372:11-20). The MR CLEAN LATE trial involving 500 patients will expand the time window up to 12 hours.
Triage of acute stroke patients
The triage of AIS patients before their arrival at the hospital also is an evolving emergency medical service issue. While the classic triage involving CT takes time, the use of scoring systems like the National Institutes of Health Stroke Scale and the Cincinnati Stroke Triage Assessment Tool, or telemedicine-based consultation, can be done faster and with less training.
Where the patient is taken first could be important. The RACECAT trial being conducted in the Catalan territory will compare transfer of acute stroke patients with suspected large-vessel occlusion to the closest local stroke center versus direct transfer to an endovascular stroke center.
Conscious sedation or general anesthesia
Some patients undergoing thrombectomy may be able to tolerate conscious sedation in place of general anesthesia. For these patients, cost-effectiveness becomes a dominant consideration. Several anesthesia trials are addressing the issue. The Sedation Versus Intubation for Endovascular Stroke Treatment (SIESTA) trial involving 150 German patients has been completed, but the findings have not been reported. The General or Local Anaesthesia in Intra-arterial Therapy (GOLIATH) trial is recruiting patients in the Netherlands, with a target enrollment of 128. Other trials are planned in China and Sweden, but recruitment has not started.
Thrombectomy alone
For patients with AIS caused by basilar artery occlusion, stroke specialists have wondered whether intra-arterial treatment, including thrombolysis and potentially thrombectomy, could be more effective than best medical therapy, including intravenous thrombolysis. The Basilar Artery International Cooperation Study (BASICS) in Europe and the BEST trial in China are two trials in the early stages of assessing this question.
A related issue is whether thrombectomy alone is better than intravenous TPA followed by thrombectomy. This issue is being addressed in another MR CLEAN trial that is designed to compare the two approaches in 500 patients randomized to one or the other treatment.
Other intravenous antithrombotic drugs
Another unresolved issue relates to the use of other antithrombotic medications delivered intravenously in combination with TPA. This could be the sole treatment strategy, or could be used in patients who also undergo endovascular thrombectomy. The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial will randomize patients to receive argatroban or eptifibatide along with TPA, or TPA alone, within 3 hours of stroke symptom onset. Endovascular therapy will be done as indicated.
Heparin use in endovascular therapy
The proper use of antithrombotics like heparin in patients treated with endovascular therapy is unclear. The MR CLEAN MED trial will assess the benefits of two doses of unfractionated heparin and aspirin alone or in combination in 1,500 patients with AIS who receive intra-arterial treatment for confirmed anterior circulation occlusion.
On the horizon
Whether neuroprotection can improve the outcome in patients who undergo embolectomy is unclear, and will be the subject of a trial in Canada that is not yet recruiting patients. Finally, the best way to manage blood pressure following embolectomy and reperfusion is also unclear.
Dr. Broderick had no relevant financial disclosures.
BALTIMORE – Endovascular therapy is a bedrock of acute ischemic stroke treatment, but some vexing issues remain unresolved, according to Joseph Broderick, MD, of the University of Cincinnati.
“We have learned a tremendous amount the last few years. We know that thrombectomy can work if initiated in patients within 6 hours of stroke onset with or without TPA [tissue plasminogen activator]. The question is what we don’t know,” Dr. Broderick said.
The good news is that clinical trials are underway or planned to address several of these issues, he said at the annual meeting of the American Neurological Association.
Mechanical thrombectomy beyond 6 hours
Whether the treatment window for thrombectomy can be safely extended in appropriately selected patients beyond 6 hours from onset is “one of the most important issues we face,” Dr. Broderick said.
Along with DEFUSE 3, the DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention (DAWN) trial will examine whether medical management that includes thrombectomy delivered up to 24 hours after AIS symptoms first appear will yield better clinical outcomes than medical management alone in appropriate patients.
The use of mechanical thrombectomy up to 12 hours after symptom development in AIS patients for whom intravenous TPA can’t be used or doesn’t work will be assessed in the Perfusion Imaging Selection of Ischemic Stroke Patients for Endovascular Therapy (POSITIVE) trial. The primary objective is to show less stroke-related disability and improved good functional outcomes, compared with those who receive best medical therapy.
The first Multicenter Randomized Clinical Trial of Endovascular Treatment in the Netherlands (MR CLEAN) trial, which used stent retrievers in almost all cases, demonstrated the benefit of endovascular therapy up to 6 hours after stroke onset in the proximal anterior circulation when used along with best medical therapy (N Engl J Med. 2015;372:11-20). The MR CLEAN LATE trial involving 500 patients will expand the time window up to 12 hours.
Triage of acute stroke patients
The triage of AIS patients before their arrival at the hospital also is an evolving emergency medical service issue. While the classic triage involving CT takes time, the use of scoring systems like the National Institutes of Health Stroke Scale and the Cincinnati Stroke Triage Assessment Tool, or telemedicine-based consultation, can be done faster and with less training.
Where the patient is taken first could be important. The RACECAT trial being conducted in the Catalan territory will compare transfer of acute stroke patients with suspected large-vessel occlusion to the closest local stroke center versus direct transfer to an endovascular stroke center.
Conscious sedation or general anesthesia
Some patients undergoing thrombectomy may be able to tolerate conscious sedation in place of general anesthesia. For these patients, cost-effectiveness becomes a dominant consideration. Several anesthesia trials are addressing the issue. The Sedation Versus Intubation for Endovascular Stroke Treatment (SIESTA) trial involving 150 German patients has been completed, but the findings have not been reported. The General or Local Anaesthesia in Intra-arterial Therapy (GOLIATH) trial is recruiting patients in the Netherlands, with a target enrollment of 128. Other trials are planned in China and Sweden, but recruitment has not started.
Thrombectomy alone
For patients with AIS caused by basilar artery occlusion, stroke specialists have wondered whether intra-arterial treatment, including thrombolysis and potentially thrombectomy, could be more effective than best medical therapy, including intravenous thrombolysis. The Basilar Artery International Cooperation Study (BASICS) in Europe and the BEST trial in China are two trials in the early stages of assessing this question.
A related issue is whether thrombectomy alone is better than intravenous TPA followed by thrombectomy. This issue is being addressed in another MR CLEAN trial that is designed to compare the two approaches in 500 patients randomized to one or the other treatment.
Other intravenous antithrombotic drugs
Another unresolved issue relates to the use of other antithrombotic medications delivered intravenously in combination with TPA. This could be the sole treatment strategy, or could be used in patients who also undergo endovascular thrombectomy. The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial will randomize patients to receive argatroban or eptifibatide along with TPA, or TPA alone, within 3 hours of stroke symptom onset. Endovascular therapy will be done as indicated.
Heparin use in endovascular therapy
The proper use of antithrombotics like heparin in patients treated with endovascular therapy is unclear. The MR CLEAN MED trial will assess the benefits of two doses of unfractionated heparin and aspirin alone or in combination in 1,500 patients with AIS who receive intra-arterial treatment for confirmed anterior circulation occlusion.
On the horizon
Whether neuroprotection can improve the outcome in patients who undergo embolectomy is unclear, and will be the subject of a trial in Canada that is not yet recruiting patients. Finally, the best way to manage blood pressure following embolectomy and reperfusion is also unclear.
Dr. Broderick had no relevant financial disclosures.
Telehealth has value in Parkinson’s and poststroke care
BALTIMORE – The broadening of access to medical care through telemedicine that’s been occurring for acute neurologic conditions such as stroke has begun to expand to care for more chronic conditions such as Parkinson’s disease and poststroke recovery, according to presentations given at the annual meeting of the American Neurological Association.
Telemedicine care for patients with Parkinson’s appears feasible and acceptable to both patients and clinicians alike, based on recent findings. Ray Dorsey, MD, of the University of Rochester (N.Y.) initiated the Connect.Parkinson study with his colleagues in 2014 to compare usual care enhanced with educational materials against others who received usual care, educational materials, and four virtual sessions with a Parkinson’s disease specialist from 1 of 18 neurology centers nationwide. Some of the participants who lived far away from one of these centers would not otherwise have received such specialized care (Telemed J E Health. 2016;22[7]:590-8).
The participating physicians had concerns about the quality of the video connection, but otherwise were satisfied with the care delivered to the patients. Surveys of participants revealed no differences between the two groups in quality of life and quality of care. About 80% of those who received virtual calls preferred this contact to the regular office visits.
The development of smartphone apps that allow aspects of diseases like Parkinson’s to be monitored are also enabling high-quality, diagnostic telecare. A pilot study of an Android smartphone Parkinson’s disease app by Dr. Dorsey and his colleagues demonstrated its utility in tests of voice, postural sway, gait, finger tapping, and reaction time (Parkinsonism Relat Disord. 2015;21[6]:650-3).
Since that study was completed, an iOS smartphone version of the app, called mPower, has been developed and has enrolled many Parkinson’s disease patients. The technology is being tested to virtually gauge Parkinson’s disease symptoms and the effects of medications on them. This has opened the door to the world of virtual clinical trials and longitudinal studies targeting genetic subpopulations, Dr. Dorsey said at the meeting.
The telehealth portion of COMPASS – in the form of regular phone calls and web-based feedback – enables better stroke care following hospital discharge by keeping track of common complications that are partly responsible for a readmittance rate of around 25% within 90 days of hospital discharge and tracking physiological aspects like blood pressure, diabetes, diet, exercise, and smoking.
The pilot demonstration of the potential of the program was pivotal in securing funding for a cluster-randomized pragmatic trial. The trial will randomize hospitals to normal discharge or discharge followed by regular poststroke contact. Patient functional status at 90 days post stroke will be assessed for 1 year. After the year, the hospitals randomized to COMPASS care delivery will continue this care, and the hospitals offering normal discharge will also adopt this poststroke service care. Patient outcome will be followed for another year.
The anticipated patient enrollment is 5,400. Results from the first year of the 2-year study are expected in Spring 2018. “COMPASS will have an impact on the post-acute stroke care pathway. After evaluating the effectiveness, the goal is to disseminate and scale to other settings,” Dr. Bushnell said at the meeting.
Dr. Dorsey receives research support from Excellus BlueCross BlueShield, Google, and the Verizon Foundation. He has received compensation for consulting services for Medtronic and owns stock options in ConsultingMD. Dr. Bushnell acknowledged salary support from the COMPASS program, which receives funding from the Patient-Centered Outcomes Research Institute.
BALTIMORE – The broadening of access to medical care through telemedicine that’s been occurring for acute neurologic conditions such as stroke has begun to expand to care for more chronic conditions such as Parkinson’s disease and poststroke recovery, according to presentations given at the annual meeting of the American Neurological Association.
Telemedicine care for patients with Parkinson’s appears feasible and acceptable to both patients and clinicians alike, based on recent findings. Ray Dorsey, MD, of the University of Rochester (N.Y.) initiated the Connect.Parkinson study with his colleagues in 2014 to compare usual care enhanced with educational materials against others who received usual care, educational materials, and four virtual sessions with a Parkinson’s disease specialist from 1 of 18 neurology centers nationwide. Some of the participants who lived far away from one of these centers would not otherwise have received such specialized care (Telemed J E Health. 2016;22[7]:590-8).
The participating physicians had concerns about the quality of the video connection, but otherwise were satisfied with the care delivered to the patients. Surveys of participants revealed no differences between the two groups in quality of life and quality of care. About 80% of those who received virtual calls preferred this contact to the regular office visits.
The development of smartphone apps that allow aspects of diseases like Parkinson’s to be monitored are also enabling high-quality, diagnostic telecare. A pilot study of an Android smartphone Parkinson’s disease app by Dr. Dorsey and his colleagues demonstrated its utility in tests of voice, postural sway, gait, finger tapping, and reaction time (Parkinsonism Relat Disord. 2015;21[6]:650-3).
Since that study was completed, an iOS smartphone version of the app, called mPower, has been developed and has enrolled many Parkinson’s disease patients. The technology is being tested to virtually gauge Parkinson’s disease symptoms and the effects of medications on them. This has opened the door to the world of virtual clinical trials and longitudinal studies targeting genetic subpopulations, Dr. Dorsey said at the meeting.
The telehealth portion of COMPASS – in the form of regular phone calls and web-based feedback – enables better stroke care following hospital discharge by keeping track of common complications that are partly responsible for a readmittance rate of around 25% within 90 days of hospital discharge and tracking physiological aspects like blood pressure, diabetes, diet, exercise, and smoking.
The pilot demonstration of the potential of the program was pivotal in securing funding for a cluster-randomized pragmatic trial. The trial will randomize hospitals to normal discharge or discharge followed by regular poststroke contact. Patient functional status at 90 days post stroke will be assessed for 1 year. After the year, the hospitals randomized to COMPASS care delivery will continue this care, and the hospitals offering normal discharge will also adopt this poststroke service care. Patient outcome will be followed for another year.
The anticipated patient enrollment is 5,400. Results from the first year of the 2-year study are expected in Spring 2018. “COMPASS will have an impact on the post-acute stroke care pathway. After evaluating the effectiveness, the goal is to disseminate and scale to other settings,” Dr. Bushnell said at the meeting.
Dr. Dorsey receives research support from Excellus BlueCross BlueShield, Google, and the Verizon Foundation. He has received compensation for consulting services for Medtronic and owns stock options in ConsultingMD. Dr. Bushnell acknowledged salary support from the COMPASS program, which receives funding from the Patient-Centered Outcomes Research Institute.
BALTIMORE – The broadening of access to medical care through telemedicine that’s been occurring for acute neurologic conditions such as stroke has begun to expand to care for more chronic conditions such as Parkinson’s disease and poststroke recovery, according to presentations given at the annual meeting of the American Neurological Association.
Telemedicine care for patients with Parkinson’s appears feasible and acceptable to both patients and clinicians alike, based on recent findings. Ray Dorsey, MD, of the University of Rochester (N.Y.) initiated the Connect.Parkinson study with his colleagues in 2014 to compare usual care enhanced with educational materials against others who received usual care, educational materials, and four virtual sessions with a Parkinson’s disease specialist from 1 of 18 neurology centers nationwide. Some of the participants who lived far away from one of these centers would not otherwise have received such specialized care (Telemed J E Health. 2016;22[7]:590-8).
The participating physicians had concerns about the quality of the video connection, but otherwise were satisfied with the care delivered to the patients. Surveys of participants revealed no differences between the two groups in quality of life and quality of care. About 80% of those who received virtual calls preferred this contact to the regular office visits.
The development of smartphone apps that allow aspects of diseases like Parkinson’s to be monitored are also enabling high-quality, diagnostic telecare. A pilot study of an Android smartphone Parkinson’s disease app by Dr. Dorsey and his colleagues demonstrated its utility in tests of voice, postural sway, gait, finger tapping, and reaction time (Parkinsonism Relat Disord. 2015;21[6]:650-3).
Since that study was completed, an iOS smartphone version of the app, called mPower, has been developed and has enrolled many Parkinson’s disease patients. The technology is being tested to virtually gauge Parkinson’s disease symptoms and the effects of medications on them. This has opened the door to the world of virtual clinical trials and longitudinal studies targeting genetic subpopulations, Dr. Dorsey said at the meeting.
The telehealth portion of COMPASS – in the form of regular phone calls and web-based feedback – enables better stroke care following hospital discharge by keeping track of common complications that are partly responsible for a readmittance rate of around 25% within 90 days of hospital discharge and tracking physiological aspects like blood pressure, diabetes, diet, exercise, and smoking.
The pilot demonstration of the potential of the program was pivotal in securing funding for a cluster-randomized pragmatic trial. The trial will randomize hospitals to normal discharge or discharge followed by regular poststroke contact. Patient functional status at 90 days post stroke will be assessed for 1 year. After the year, the hospitals randomized to COMPASS care delivery will continue this care, and the hospitals offering normal discharge will also adopt this poststroke service care. Patient outcome will be followed for another year.
The anticipated patient enrollment is 5,400. Results from the first year of the 2-year study are expected in Spring 2018. “COMPASS will have an impact on the post-acute stroke care pathway. After evaluating the effectiveness, the goal is to disseminate and scale to other settings,” Dr. Bushnell said at the meeting.
Dr. Dorsey receives research support from Excellus BlueCross BlueShield, Google, and the Verizon Foundation. He has received compensation for consulting services for Medtronic and owns stock options in ConsultingMD. Dr. Bushnell acknowledged salary support from the COMPASS program, which receives funding from the Patient-Centered Outcomes Research Institute.
EXPERT ANALYSIS FROM ANA 2016
Computed tomography angiography after NCCT delays thrombectomy
BALTIMORE – Performing computed tomography angiography (CTA) following noncontrast computed tomography (NCCT) to obtain a high-resolution image of the large-vessel occlusion significantly delays the time to thrombectomy.
In clinical practice, omitting CTA in patients whose middle cerebral artery visualized on NCCT reveals the hyperdense sign may speed the time to thrombectomy and improve outcome. The findings of a retrospective cohort study of prospectively collected data were presented by Kunakorn Atchaneeyasakul, MD, of the University of Miami, as a poster and a brief oral presentation at the annual meeting of the American Neurological Association.
This study retrospectively compared the time from imaging to groin puncture, which is the first step in thrombectomy, in patients who received NCCT followed by CTA with those who received just NCCT for anterior circulation occlusion at the tertiary care University of Miami medical center. Of the 289 patients who received thrombectomy, 255 were excluded because of transfer from another hospital, occurrence of stroke while hospitalized, or use of other imaging prior to thrombectomy.
The remaining 34 patients were all evaluated with thin (0.625-mm) NCCT with automated image reconstruction. Fourteen received NCCT only, and 20 received CTA in addition to NCCT. The two groups were similar in mean age (64-71 years), gender (50% were female in each group), prevalence of hypertension (64% and 70% in the NCCT and NCCT + CTA group, respectively), and prevalence of diabetes, hyperlipidemia, atrial fibrillation, smoking, occlusion site, modified Rankin Scale score at discharge, and National Institutes of Health Stroke Scale scores at presentation and discharge. All 14 NCCT patients received intravenous tPA in contrast to 11 of the 20 (55%) NCCT + CTA patients (P = .003).
The middle cerebral artery was visualized on NCCT in about 85% of patients in each treatment group. Reperfusion was successful in 64% and 80% of patients receiving NCCT and NCCT + CTA, respectively (P = .31).
The total duration of imaging was 2 minutes (range, 1-6) in the NCCT group. The duration was significantly longer in the NCCT + CTA group (28 minutes; range, 23-65; P less than .001). The time from imaging to groin puncture was 68 minutes (range, 32-99) in the NCCT group. This was more than 30 minutes shorter than the NCCT + CTA group (104 minutes; range, 79-128; P = .030).
The times from emergency department admission to NCCT and from admission to groin puncture were similar in both groups.
“Avoiding advanced imaging in patients with anterior circulation large-vessel occlusion in whom thin-section NCCT with maximum-intensity projections reveals a hyperdense sign significantly shortens the imaging to groin puncture time,” concluded Dr. Atchaneeyasakul.
In the scenario, the detection of hyperdense middle cerebral artery would fast track the patient to the angiography suite, forgoing CTA. The result, according to Dr. Atchaneeyasakul, could alleviate a delay in thrombectomy, which could better preserve brain function.
Funding information was not provided.
BALTIMORE – Performing computed tomography angiography (CTA) following noncontrast computed tomography (NCCT) to obtain a high-resolution image of the large-vessel occlusion significantly delays the time to thrombectomy.
In clinical practice, omitting CTA in patients whose middle cerebral artery visualized on NCCT reveals the hyperdense sign may speed the time to thrombectomy and improve outcome. The findings of a retrospective cohort study of prospectively collected data were presented by Kunakorn Atchaneeyasakul, MD, of the University of Miami, as a poster and a brief oral presentation at the annual meeting of the American Neurological Association.
This study retrospectively compared the time from imaging to groin puncture, which is the first step in thrombectomy, in patients who received NCCT followed by CTA with those who received just NCCT for anterior circulation occlusion at the tertiary care University of Miami medical center. Of the 289 patients who received thrombectomy, 255 were excluded because of transfer from another hospital, occurrence of stroke while hospitalized, or use of other imaging prior to thrombectomy.
The remaining 34 patients were all evaluated with thin (0.625-mm) NCCT with automated image reconstruction. Fourteen received NCCT only, and 20 received CTA in addition to NCCT. The two groups were similar in mean age (64-71 years), gender (50% were female in each group), prevalence of hypertension (64% and 70% in the NCCT and NCCT + CTA group, respectively), and prevalence of diabetes, hyperlipidemia, atrial fibrillation, smoking, occlusion site, modified Rankin Scale score at discharge, and National Institutes of Health Stroke Scale scores at presentation and discharge. All 14 NCCT patients received intravenous tPA in contrast to 11 of the 20 (55%) NCCT + CTA patients (P = .003).
The middle cerebral artery was visualized on NCCT in about 85% of patients in each treatment group. Reperfusion was successful in 64% and 80% of patients receiving NCCT and NCCT + CTA, respectively (P = .31).
The total duration of imaging was 2 minutes (range, 1-6) in the NCCT group. The duration was significantly longer in the NCCT + CTA group (28 minutes; range, 23-65; P less than .001). The time from imaging to groin puncture was 68 minutes (range, 32-99) in the NCCT group. This was more than 30 minutes shorter than the NCCT + CTA group (104 minutes; range, 79-128; P = .030).
The times from emergency department admission to NCCT and from admission to groin puncture were similar in both groups.
“Avoiding advanced imaging in patients with anterior circulation large-vessel occlusion in whom thin-section NCCT with maximum-intensity projections reveals a hyperdense sign significantly shortens the imaging to groin puncture time,” concluded Dr. Atchaneeyasakul.
In the scenario, the detection of hyperdense middle cerebral artery would fast track the patient to the angiography suite, forgoing CTA. The result, according to Dr. Atchaneeyasakul, could alleviate a delay in thrombectomy, which could better preserve brain function.
Funding information was not provided.
BALTIMORE – Performing computed tomography angiography (CTA) following noncontrast computed tomography (NCCT) to obtain a high-resolution image of the large-vessel occlusion significantly delays the time to thrombectomy.
In clinical practice, omitting CTA in patients whose middle cerebral artery visualized on NCCT reveals the hyperdense sign may speed the time to thrombectomy and improve outcome. The findings of a retrospective cohort study of prospectively collected data were presented by Kunakorn Atchaneeyasakul, MD, of the University of Miami, as a poster and a brief oral presentation at the annual meeting of the American Neurological Association.
This study retrospectively compared the time from imaging to groin puncture, which is the first step in thrombectomy, in patients who received NCCT followed by CTA with those who received just NCCT for anterior circulation occlusion at the tertiary care University of Miami medical center. Of the 289 patients who received thrombectomy, 255 were excluded because of transfer from another hospital, occurrence of stroke while hospitalized, or use of other imaging prior to thrombectomy.
The remaining 34 patients were all evaluated with thin (0.625-mm) NCCT with automated image reconstruction. Fourteen received NCCT only, and 20 received CTA in addition to NCCT. The two groups were similar in mean age (64-71 years), gender (50% were female in each group), prevalence of hypertension (64% and 70% in the NCCT and NCCT + CTA group, respectively), and prevalence of diabetes, hyperlipidemia, atrial fibrillation, smoking, occlusion site, modified Rankin Scale score at discharge, and National Institutes of Health Stroke Scale scores at presentation and discharge. All 14 NCCT patients received intravenous tPA in contrast to 11 of the 20 (55%) NCCT + CTA patients (P = .003).
The middle cerebral artery was visualized on NCCT in about 85% of patients in each treatment group. Reperfusion was successful in 64% and 80% of patients receiving NCCT and NCCT + CTA, respectively (P = .31).
The total duration of imaging was 2 minutes (range, 1-6) in the NCCT group. The duration was significantly longer in the NCCT + CTA group (28 minutes; range, 23-65; P less than .001). The time from imaging to groin puncture was 68 minutes (range, 32-99) in the NCCT group. This was more than 30 minutes shorter than the NCCT + CTA group (104 minutes; range, 79-128; P = .030).
The times from emergency department admission to NCCT and from admission to groin puncture were similar in both groups.
“Avoiding advanced imaging in patients with anterior circulation large-vessel occlusion in whom thin-section NCCT with maximum-intensity projections reveals a hyperdense sign significantly shortens the imaging to groin puncture time,” concluded Dr. Atchaneeyasakul.
In the scenario, the detection of hyperdense middle cerebral artery would fast track the patient to the angiography suite, forgoing CTA. The result, according to Dr. Atchaneeyasakul, could alleviate a delay in thrombectomy, which could better preserve brain function.
Funding information was not provided.
AT ANA 2016
Key clinical point:
Major finding: Time from imaging to groin puncture was 68 minutes for NCCT vs. 104 minutes for NCCT + CTA.
Data source: Retrospective cohort study of prospectively collected data.
Disclosures: Dr. Atchaneeyasakul had no disclosures.
Genetic risk score for low vitamin D may affect MS relapse rate
BALTIMORE – A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detected multiple sclerosis patients with an increased risk for relapse in a multicenter cohort study.
The findings could have clinical significance in multiple sclerosis (MS) treatment and patient counseling, Jennifer S. Graves, MD, PhD, of the University of California, San Francisco, said in a brief oral and poster presentation of the study at the annual meeting of the American Neurological Association.
The investigators compared the SNP profile of a discovery cohort of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) who were enrolled at two pediatric MS centers in California between 2006 and 2011 against a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level who were enrolled at nine MS centers elsewhere in the United States from 2011 to 2015.
Three of the SNPs were strongly associated with the vitamin D levels in the discovery cohort after a statistical correction that revealed individual influences of genes among the 29 different mutations. The researchers used these three SNPs to generate risk scores for vitamin D levels. A comparison of the lowest and highest scores revealed a linear association with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in both the discovery and replication cohorts (P = .00000052 and .002, respectively).
The risk of MS relapse for individuals with the highest risk score in the discovery cohort was nearly twice as high as it was for individuals with the lowest risk score (hazard ratio, 1.94; 95% confidence interval, 1.19-3.15; P = .007).
“A genetic score of three functional SNPs captures risk of low vitamin D level and identifies those who may be at risk of relapse related to this risk factor. These findings support a causal association of vitamin D with relapse rate,” Dr. Graves said.
The study may potentially be important beyond MS. “This risk score may also have some utility in other disease states where vitamin D deficiency may be contributing to disease course,” she said.
The study was funded by The Race to Erase MS, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Graves had no disclosures.
BALTIMORE – A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detected multiple sclerosis patients with an increased risk for relapse in a multicenter cohort study.
The findings could have clinical significance in multiple sclerosis (MS) treatment and patient counseling, Jennifer S. Graves, MD, PhD, of the University of California, San Francisco, said in a brief oral and poster presentation of the study at the annual meeting of the American Neurological Association.
The investigators compared the SNP profile of a discovery cohort of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) who were enrolled at two pediatric MS centers in California between 2006 and 2011 against a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level who were enrolled at nine MS centers elsewhere in the United States from 2011 to 2015.
Three of the SNPs were strongly associated with the vitamin D levels in the discovery cohort after a statistical correction that revealed individual influences of genes among the 29 different mutations. The researchers used these three SNPs to generate risk scores for vitamin D levels. A comparison of the lowest and highest scores revealed a linear association with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in both the discovery and replication cohorts (P = .00000052 and .002, respectively).
The risk of MS relapse for individuals with the highest risk score in the discovery cohort was nearly twice as high as it was for individuals with the lowest risk score (hazard ratio, 1.94; 95% confidence interval, 1.19-3.15; P = .007).
“A genetic score of three functional SNPs captures risk of low vitamin D level and identifies those who may be at risk of relapse related to this risk factor. These findings support a causal association of vitamin D with relapse rate,” Dr. Graves said.
The study may potentially be important beyond MS. “This risk score may also have some utility in other disease states where vitamin D deficiency may be contributing to disease course,” she said.
The study was funded by The Race to Erase MS, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Graves had no disclosures.
BALTIMORE – A genetic scoring system for identifying individuals at high risk for low vitamin D levels also detected multiple sclerosis patients with an increased risk for relapse in a multicenter cohort study.
The findings could have clinical significance in multiple sclerosis (MS) treatment and patient counseling, Jennifer S. Graves, MD, PhD, of the University of California, San Francisco, said in a brief oral and poster presentation of the study at the annual meeting of the American Neurological Association.
The investigators compared the SNP profile of a discovery cohort of 181 patients with MS or high-risk clinically isolated syndrome (the discovery cohort) who were enrolled at two pediatric MS centers in California between 2006 and 2011 against a replication cohort of 110 patients of comparable age, race, and median vitamin D serum level who were enrolled at nine MS centers elsewhere in the United States from 2011 to 2015.
Three of the SNPs were strongly associated with the vitamin D levels in the discovery cohort after a statistical correction that revealed individual influences of genes among the 29 different mutations. The researchers used these three SNPs to generate risk scores for vitamin D levels. A comparison of the lowest and highest scores revealed a linear association with vitamin D levels. The highest scores were associated with serum vitamin D levels that were nearly 15 ng/mL lower in both the discovery and replication cohorts (P = .00000052 and .002, respectively).
The risk of MS relapse for individuals with the highest risk score in the discovery cohort was nearly twice as high as it was for individuals with the lowest risk score (hazard ratio, 1.94; 95% confidence interval, 1.19-3.15; P = .007).
“A genetic score of three functional SNPs captures risk of low vitamin D level and identifies those who may be at risk of relapse related to this risk factor. These findings support a causal association of vitamin D with relapse rate,” Dr. Graves said.
The study may potentially be important beyond MS. “This risk score may also have some utility in other disease states where vitamin D deficiency may be contributing to disease course,” she said.
The study was funded by The Race to Erase MS, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Graves had no disclosures.
AT ANA 2016
Key clinical point:
Major finding: The risk of MS relapse was 94% greater for individuals with the highest genetic risk score for low serum vitamin D level, compared with those who had the lowest risk score.
Data source: Databases of patients enrolled at two pediatric MS centers in California and nine national MS centers.
Disclosures: The study was funded by The Race to Erase MS, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Graves had no disclosures.
Earlier ischemic stroke presentation may sometimes mean delayed tPA
BALTIMORE – Going to the hospital soon after the development of symptoms of acute ischemic stroke may not guarantee quick treatment.
A study of 1,865 patients treated within the past decade at a large urban comprehensive stroke center has revealed delayed treatment with tissue plasminogen activator, compared with patients who came to the emergency room hours after symptom development, Dr. Kyle C. Rossi said at the annual meeting of the American Neurological Association.
Treatment with tissue plasminogen activator (tPA) within 3 hours after the first symptoms of acute ischemic stroke definitely improves long-term outcomes, but meeting this target time remains a challenge. Patients who present to the emergency room soon after symptom development would seemingly have an advantage, yet Dr. Rossi’s preliminary scrutiny of patient records at Mount Sinai raised doubts about this and prompted the present study.
The hypothesis was that cases with a shorter time between symptom development and diagnosis of stroke (last known well-to-stroke code time, or LKW-to-code) will have a longer time between diagnosis and tPA administration (code-to-tPA), “possibly due to the perception on the part of evaluating physicians of sufficient remaining time before the end of the tPA window.”
The researchers examined patient records from the American Heart Association/American Stroke Association’s “Get with the Guidelines” stroke program, a voluntary observational registry for patients with acute stroke. Of the 1,865 ischemic stroke patients treated during 2009-2015, 122 who received intravenous tPA were allocated to three LKW-to-code groups: within an hour (38 patients), within the next hour (49 patients), or 2 hours or more (35 patients).
The patients tended to be in their late 60s. Just over half were female, and about 40% were white.
Overall, the average LKW-to-code time was 91 ± 48 minutes and the average code-to-tPA time was 67 ± 26 minutes.
Average code-to-tPA times were 80, 67, and 52 minutes, respectively, for the three groups (P less than .0001). On average, it took 28 minutes longer to give tPA to patients who presented within an hour than to patients presenting 2 hours or longer after their first stroke symptom. There was an increase in code-to-tPA time of 1 minute for every decrease in LKW-to-code time of 4 minutes (P less than .0001).
The delay in the time to treat patients who arrive sooner after development of stroke symptoms may result from a decision made by the evaluating neurologist to conduct additional testing prior to administering tPA. Sometimes other staff may be unaware of the decision to delay treatment, according to Dr. Rossi and his colleagues.
“Absolutely, folks coming in soon after symptoms develop should be treated early. But treatment needs to balance rapid delivery with adequate testing. Sometimes, when there is some time to spare before the optimum treatment window closes we can do a more thorough examination and address lingering questions,” Dr. Rossi said.
The decision to get more information about the patient’s condition reflects the goal to give tPA as soon as safely possible to the right patients. While laudable, the study highlights that the timing of treatment can be improved.
Dr. Rossi reported having no financial disclosures.
BALTIMORE – Going to the hospital soon after the development of symptoms of acute ischemic stroke may not guarantee quick treatment.
A study of 1,865 patients treated within the past decade at a large urban comprehensive stroke center has revealed delayed treatment with tissue plasminogen activator, compared with patients who came to the emergency room hours after symptom development, Dr. Kyle C. Rossi said at the annual meeting of the American Neurological Association.
Treatment with tissue plasminogen activator (tPA) within 3 hours after the first symptoms of acute ischemic stroke definitely improves long-term outcomes, but meeting this target time remains a challenge. Patients who present to the emergency room soon after symptom development would seemingly have an advantage, yet Dr. Rossi’s preliminary scrutiny of patient records at Mount Sinai raised doubts about this and prompted the present study.
The hypothesis was that cases with a shorter time between symptom development and diagnosis of stroke (last known well-to-stroke code time, or LKW-to-code) will have a longer time between diagnosis and tPA administration (code-to-tPA), “possibly due to the perception on the part of evaluating physicians of sufficient remaining time before the end of the tPA window.”
The researchers examined patient records from the American Heart Association/American Stroke Association’s “Get with the Guidelines” stroke program, a voluntary observational registry for patients with acute stroke. Of the 1,865 ischemic stroke patients treated during 2009-2015, 122 who received intravenous tPA were allocated to three LKW-to-code groups: within an hour (38 patients), within the next hour (49 patients), or 2 hours or more (35 patients).
The patients tended to be in their late 60s. Just over half were female, and about 40% were white.
Overall, the average LKW-to-code time was 91 ± 48 minutes and the average code-to-tPA time was 67 ± 26 minutes.
Average code-to-tPA times were 80, 67, and 52 minutes, respectively, for the three groups (P less than .0001). On average, it took 28 minutes longer to give tPA to patients who presented within an hour than to patients presenting 2 hours or longer after their first stroke symptom. There was an increase in code-to-tPA time of 1 minute for every decrease in LKW-to-code time of 4 minutes (P less than .0001).
The delay in the time to treat patients who arrive sooner after development of stroke symptoms may result from a decision made by the evaluating neurologist to conduct additional testing prior to administering tPA. Sometimes other staff may be unaware of the decision to delay treatment, according to Dr. Rossi and his colleagues.
“Absolutely, folks coming in soon after symptoms develop should be treated early. But treatment needs to balance rapid delivery with adequate testing. Sometimes, when there is some time to spare before the optimum treatment window closes we can do a more thorough examination and address lingering questions,” Dr. Rossi said.
The decision to get more information about the patient’s condition reflects the goal to give tPA as soon as safely possible to the right patients. While laudable, the study highlights that the timing of treatment can be improved.
Dr. Rossi reported having no financial disclosures.
BALTIMORE – Going to the hospital soon after the development of symptoms of acute ischemic stroke may not guarantee quick treatment.
A study of 1,865 patients treated within the past decade at a large urban comprehensive stroke center has revealed delayed treatment with tissue plasminogen activator, compared with patients who came to the emergency room hours after symptom development, Dr. Kyle C. Rossi said at the annual meeting of the American Neurological Association.
Treatment with tissue plasminogen activator (tPA) within 3 hours after the first symptoms of acute ischemic stroke definitely improves long-term outcomes, but meeting this target time remains a challenge. Patients who present to the emergency room soon after symptom development would seemingly have an advantage, yet Dr. Rossi’s preliminary scrutiny of patient records at Mount Sinai raised doubts about this and prompted the present study.
The hypothesis was that cases with a shorter time between symptom development and diagnosis of stroke (last known well-to-stroke code time, or LKW-to-code) will have a longer time between diagnosis and tPA administration (code-to-tPA), “possibly due to the perception on the part of evaluating physicians of sufficient remaining time before the end of the tPA window.”
The researchers examined patient records from the American Heart Association/American Stroke Association’s “Get with the Guidelines” stroke program, a voluntary observational registry for patients with acute stroke. Of the 1,865 ischemic stroke patients treated during 2009-2015, 122 who received intravenous tPA were allocated to three LKW-to-code groups: within an hour (38 patients), within the next hour (49 patients), or 2 hours or more (35 patients).
The patients tended to be in their late 60s. Just over half were female, and about 40% were white.
Overall, the average LKW-to-code time was 91 ± 48 minutes and the average code-to-tPA time was 67 ± 26 minutes.
Average code-to-tPA times were 80, 67, and 52 minutes, respectively, for the three groups (P less than .0001). On average, it took 28 minutes longer to give tPA to patients who presented within an hour than to patients presenting 2 hours or longer after their first stroke symptom. There was an increase in code-to-tPA time of 1 minute for every decrease in LKW-to-code time of 4 minutes (P less than .0001).
The delay in the time to treat patients who arrive sooner after development of stroke symptoms may result from a decision made by the evaluating neurologist to conduct additional testing prior to administering tPA. Sometimes other staff may be unaware of the decision to delay treatment, according to Dr. Rossi and his colleagues.
“Absolutely, folks coming in soon after symptoms develop should be treated early. But treatment needs to balance rapid delivery with adequate testing. Sometimes, when there is some time to spare before the optimum treatment window closes we can do a more thorough examination and address lingering questions,” Dr. Rossi said.
The decision to get more information about the patient’s condition reflects the goal to give tPA as soon as safely possible to the right patients. While laudable, the study highlights that the timing of treatment can be improved.
Dr. Rossi reported having no financial disclosures.
AT ANA 2016
Key clinical point:
Major finding: TPA was delivered 28 minutes longer on average for patients presenting less than 1 hour after stroke symptoms, compared with patients presenting more than 2 hours after.
Data source: Analysis of 1,865 patients with acute ischemic stroke in the American Heart Association/American Stroke Association’s “Get with the Guidelines” stroke program who were diagnosed at Mount Sinai Hospital in New York.
Disclosures: Dr. Rossi reported having no financial disclosures.
Longer hospitalization, greater care needed for depressed ischemic stroke patients
BALTIMORE – Patients admitted with acute ischemic stroke (AIS) with preexisting major depressive disorder (MDD) are less likely to die while in the hospital but are often hospitalized longer and are more likely to need specialty care when they are discharged, in comparison to similar patients without depression in the National Inpatient Sample.
“Our study displayed an increasing proportion of patients with MDD admitted due to AIS in the last decade with lower mortality but higher morbidity post stroke. In addition, there was less utilization of thrombolysis in this population,” study presenter Arpita Hazra, MD, Northwell Health, Jersey City, N.J., said at the annual meeting of the American Neurological Association.
Thrombolysis was carried out in fewer depressed patients than in those without depression (3.8% vs. 4.8%; P less than .001). The odds of death during hospitalization were 36% less for patients with MDD. However, patients with MDD tended to be hospitalized longer than nondepressed patients (median 3.6 vs. 3.4 days; P less than .001) and were nearly 40% more likely to require specialty care following discharge.
“There is a need to explore the reasons behind this disparity in outcomes and thrombolysis utilization in order to improve poststroke outcome in this vulnerable population,” Dr. Hazra said.
At face value, the observation of decreased mortality in AIS patients with preexisting MDD was surprising, according to Dr. Hazra. She suggested that this may reflect prior hospital treatment for these patients, because of other comorbidities associated with depression.
Dr. Hazra reported having no financial disclosures.
BALTIMORE – Patients admitted with acute ischemic stroke (AIS) with preexisting major depressive disorder (MDD) are less likely to die while in the hospital but are often hospitalized longer and are more likely to need specialty care when they are discharged, in comparison to similar patients without depression in the National Inpatient Sample.
“Our study displayed an increasing proportion of patients with MDD admitted due to AIS in the last decade with lower mortality but higher morbidity post stroke. In addition, there was less utilization of thrombolysis in this population,” study presenter Arpita Hazra, MD, Northwell Health, Jersey City, N.J., said at the annual meeting of the American Neurological Association.
Thrombolysis was carried out in fewer depressed patients than in those without depression (3.8% vs. 4.8%; P less than .001). The odds of death during hospitalization were 36% less for patients with MDD. However, patients with MDD tended to be hospitalized longer than nondepressed patients (median 3.6 vs. 3.4 days; P less than .001) and were nearly 40% more likely to require specialty care following discharge.
“There is a need to explore the reasons behind this disparity in outcomes and thrombolysis utilization in order to improve poststroke outcome in this vulnerable population,” Dr. Hazra said.
At face value, the observation of decreased mortality in AIS patients with preexisting MDD was surprising, according to Dr. Hazra. She suggested that this may reflect prior hospital treatment for these patients, because of other comorbidities associated with depression.
Dr. Hazra reported having no financial disclosures.
BALTIMORE – Patients admitted with acute ischemic stroke (AIS) with preexisting major depressive disorder (MDD) are less likely to die while in the hospital but are often hospitalized longer and are more likely to need specialty care when they are discharged, in comparison to similar patients without depression in the National Inpatient Sample.
“Our study displayed an increasing proportion of patients with MDD admitted due to AIS in the last decade with lower mortality but higher morbidity post stroke. In addition, there was less utilization of thrombolysis in this population,” study presenter Arpita Hazra, MD, Northwell Health, Jersey City, N.J., said at the annual meeting of the American Neurological Association.
Thrombolysis was carried out in fewer depressed patients than in those without depression (3.8% vs. 4.8%; P less than .001). The odds of death during hospitalization were 36% less for patients with MDD. However, patients with MDD tended to be hospitalized longer than nondepressed patients (median 3.6 vs. 3.4 days; P less than .001) and were nearly 40% more likely to require specialty care following discharge.
“There is a need to explore the reasons behind this disparity in outcomes and thrombolysis utilization in order to improve poststroke outcome in this vulnerable population,” Dr. Hazra said.
At face value, the observation of decreased mortality in AIS patients with preexisting MDD was surprising, according to Dr. Hazra. She suggested that this may reflect prior hospital treatment for these patients, because of other comorbidities associated with depression.
Dr. Hazra reported having no financial disclosures.
AT ANA 2016
Key clinical point:
Major finding: In-hospital mortality was significantly lower for depressed patients with acute ischemic stroke, compared with nondepressed patients, but depressed patients had a significantly longer length of hospitalization and higher rate of discharge to specialty care.
Data source: Study of 4.3 million hospital AIS-related admissions identified in the United States during 2002-2012 in the National Inpatient Sample.
Disclosures: Dr. Hazra reported having no financial disclosures.