Pregnancy is generally found to offer a respite from multiple sclerosis (MS). Pregnant women rarely develop MS or to have relapses. But in a unique and challenging case, a woman in her 14th week of her second pregnancy developed signs and symptoms of tumefactive multiple sclerosis (TMS), a rare subtype of MS. The TMS was only one of several unexpected clinical puzzles, according to the clinicians reporting on the case.

The patient, who had been healthy, was admitted with acute onset of paresthesias and word-finding difficulty. She had just had a long drive from Florida, and the the clinicians first assumed that she was fatigued from the trip and from the pregnancy. A magnetic resonance imaging (MRI) scan of the brain, however, suggested an ischemic event.

While hospitalized, the patient’s condition rapidly worsened. More scan and test findings proved consistent with TMS. A repeat MRI scan showed interval progression with a growing tumefactive demyelinating lesion (TDL) with diffuse surrounding edema and new periventricular signal changes. Although rare, TDLs often represent fulminant forms of MS, the clinicians note. Because the lesions mimic strokes, tumors, and abscesses, diagnosis is difficult. Moreover, the gadolinium (which was avoided because it can cause birth defects) might have helped them visualize lesions sooner.

The patient was started on high-dose IV methylprednisolone and plasma exchange, but the response was mild. The poor response to both treatment modalities is infrequent in TMS, the clinicians say—yet another unforeseen obstacle.

In addition to counseling the patient about the usual protective effects of pregnancy, her clinicians counseled her “extensively” about natalizumab and the possible beneficial effects of disease-modifying therapies. But the patient made the difficult decision to terminate the pregnancy, in part because she felt it was better to focus on her existing child rather than on caring for 2 young children while having a chronic progressive disease with uncertain recovery.

Another surprise was in store. Within 12 hours after an uncomplicated dilatation and curettage, the patient was able to move her right arm. That “drastic improvement” was followed by moderate improvement in her right leg. Her “paradoxical” improvement after the termination might indicate a “different from expected” hormonal influence in the pathogenesis of TMS, the clinicians say, but more likely represents a delayed corroborating effect of steroids and plasma exchange.

In the following weeks, the patient’s recovery was “satisfying” with gradual improvement and partial return of expressive language.  Eighteen months later, the patient was clinically stable on natalizumab.

Source:
Pakneshan S, Bernitsas E. BMJ Case Rep. 2017. pii: bcr-2017-219534.
 doi: 10.1136/bcr-2017-219534.

Pregnancy is generally found to offer a respite from multiple sclerosis (MS). Pregnant women rarely develop MS or to have relapses. But in a unique and challenging case, a woman in her 14th week of her second pregnancy developed signs and symptoms of tumefactive multiple sclerosis (TMS), a rare subtype of MS. The TMS was only one of several unexpected clinical puzzles, according to the clinicians reporting on the case.

The patient, who had been healthy, was admitted with acute onset of paresthesias and word-finding difficulty. She had just had a long drive from Florida, and the the clinicians first assumed that she was fatigued from the trip and from the pregnancy. A magnetic resonance imaging (MRI) scan of the brain, however, suggested an ischemic event.

While hospitalized, the patient’s condition rapidly worsened. More scan and test findings proved consistent with TMS. A repeat MRI scan showed interval progression with a growing tumefactive demyelinating lesion (TDL) with diffuse surrounding edema and new periventricular signal changes. Although rare, TDLs often represent fulminant forms of MS, the clinicians note. Because the lesions mimic strokes, tumors, and abscesses, diagnosis is difficult. Moreover, the gadolinium (which was avoided because it can cause birth defects) might have helped them visualize lesions sooner.

The patient was started on high-dose IV methylprednisolone and plasma exchange, but the response was mild. The poor response to both treatment modalities is infrequent in TMS, the clinicians say—yet another unforeseen obstacle.

In addition to counseling the patient about the usual protective effects of pregnancy, her clinicians counseled her “extensively” about natalizumab and the possible beneficial effects of disease-modifying therapies. But the patient made the difficult decision to terminate the pregnancy, in part because she felt it was better to focus on her existing child rather than on caring for 2 young children while having a chronic progressive disease with uncertain recovery.

Another surprise was in store. Within 12 hours after an uncomplicated dilatation and curettage, the patient was able to move her right arm. That “drastic improvement” was followed by moderate improvement in her right leg. Her “paradoxical” improvement after the termination might indicate a “different from expected” hormonal influence in the pathogenesis of TMS, the clinicians say, but more likely represents a delayed corroborating effect of steroids and plasma exchange.

In the following weeks, the patient’s recovery was “satisfying” with gradual improvement and partial return of expressive language.  Eighteen months later, the patient was clinically stable on natalizumab.

Source:
Pakneshan S, Bernitsas E. BMJ Case Rep. 2017. pii: bcr-2017-219534.
 doi: 10.1136/bcr-2017-219534.

Pregnancy is generally found to offer a respite from multiple sclerosis (MS). Pregnant women rarely develop MS or to have relapses. But in a unique and challenging case, a woman in her 14th week of her second pregnancy developed signs and symptoms of tumefactive multiple sclerosis (TMS), a rare subtype of MS. The TMS was only one of several unexpected clinical puzzles, according to the clinicians reporting on the case.

The patient, who had been healthy, was admitted with acute onset of paresthesias and word-finding difficulty. She had just had a long drive from Florida, and the the clinicians first assumed that she was fatigued from the trip and from the pregnancy. A magnetic resonance imaging (MRI) scan of the brain, however, suggested an ischemic event.

While hospitalized, the patient’s condition rapidly worsened. More scan and test findings proved consistent with TMS. A repeat MRI scan showed interval progression with a growing tumefactive demyelinating lesion (TDL) with diffuse surrounding edema and new periventricular signal changes. Although rare, TDLs often represent fulminant forms of MS, the clinicians note. Because the lesions mimic strokes, tumors, and abscesses, diagnosis is difficult. Moreover, the gadolinium (which was avoided because it can cause birth defects) might have helped them visualize lesions sooner.

The patient was started on high-dose IV methylprednisolone and plasma exchange, but the response was mild. The poor response to both treatment modalities is infrequent in TMS, the clinicians say—yet another unforeseen obstacle.

In addition to counseling the patient about the usual protective effects of pregnancy, her clinicians counseled her “extensively” about natalizumab and the possible beneficial effects of disease-modifying therapies. But the patient made the difficult decision to terminate the pregnancy, in part because she felt it was better to focus on her existing child rather than on caring for 2 young children while having a chronic progressive disease with uncertain recovery.

Another surprise was in store. Within 12 hours after an uncomplicated dilatation and curettage, the patient was able to move her right arm. That “drastic improvement” was followed by moderate improvement in her right leg. Her “paradoxical” improvement after the termination might indicate a “different from expected” hormonal influence in the pathogenesis of TMS, the clinicians say, but more likely represents a delayed corroborating effect of steroids and plasma exchange.

In the following weeks, the patient’s recovery was “satisfying” with gradual improvement and partial return of expressive language.  Eighteen months later, the patient was clinically stable on natalizumab.

Source:
Pakneshan S, Bernitsas E. BMJ Case Rep. 2017. pii: bcr-2017-219534.
 doi: 10.1136/bcr-2017-219534.

Micrograph showing HL

Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).

The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.

Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.

Brentuximab vedotin is currently not approved as a frontline therapy for HL.

“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.

Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.

Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.

ECHELON-1

ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.

The trial enrolled 1334 patients with histologically confirmed advanced HL.

The primary endpoint is mPFS by independent review facility.

The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.

They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.

Secondary endpoints include overall survival (OS), CR, and safety.

The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).

Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.

The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.

Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.

Febrile neutropenia was reduced with the use of prophylactic growth factors.

Peripheral neuropathy was managed through dose modifications.

Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.

The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.

Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.

Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.

For more on brentuximab vedotin, see the full prescribing informtion. 

Micrograph showing HL

Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).

The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.

Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.

Brentuximab vedotin is currently not approved as a frontline therapy for HL.

“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.

Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.

Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.

ECHELON-1

ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.

The trial enrolled 1334 patients with histologically confirmed advanced HL.

The primary endpoint is mPFS by independent review facility.

The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.

They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.

Secondary endpoints include overall survival (OS), CR, and safety.

The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).

Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.

The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.

Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.

Febrile neutropenia was reduced with the use of prophylactic growth factors.

Peripheral neuropathy was managed through dose modifications.

Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.

The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.

Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.

Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.

For more on brentuximab vedotin, see the full prescribing informtion. 

Micrograph showing HL

Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).

The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.

Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.

Brentuximab vedotin is currently not approved as a frontline therapy for HL.

“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.

Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.

Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.

ECHELON-1

ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.

The trial enrolled 1334 patients with histologically confirmed advanced HL.

The primary endpoint is mPFS by independent review facility.

The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.

They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.

Secondary endpoints include overall survival (OS), CR, and safety.

The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).

Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.

The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.

Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.

Febrile neutropenia was reduced with the use of prophylactic growth factors.

Peripheral neuropathy was managed through dose modifications.

Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.

The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.

Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.

Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.

For more on brentuximab vedotin, see the full prescribing informtion. 

Boston Children’s Hospital is the country’s top hospital for children, according to U.S. New & World Report.

This marks the 3rd consecutive year and the fifth time in 6 years that Boston Children’s Hospital either has earned the honor on its own or been tied for the top spot. This year’s second-place finisher, Children’s Hospital of Philadelphia, was first in 2013-2014 and tied for first in 2014-2015 and 2012-2013.

[email protected]

Boston Children’s Hospital is the country’s top hospital for children, according to U.S. New & World Report.

This marks the 3rd consecutive year and the fifth time in 6 years that Boston Children’s Hospital either has earned the honor on its own or been tied for the top spot. This year’s second-place finisher, Children’s Hospital of Philadelphia, was first in 2013-2014 and tied for first in 2014-2015 and 2012-2013.

[email protected]

Boston Children’s Hospital is the country’s top hospital for children, according to U.S. New & World Report.

This marks the 3rd consecutive year and the fifth time in 6 years that Boston Children’s Hospital either has earned the honor on its own or been tied for the top spot. This year’s second-place finisher, Children’s Hospital of Philadelphia, was first in 2013-2014 and tied for first in 2014-2015 and 2012-2013.

[email protected]

In nine pediatric dosing trials, more than 80% of parents made more than one medication dosing error, according to a study by H. Shonna Yin, MD, and associates. Misunderstandings about how to accurately choose the right dosing tools as well as confusion related to units of measure contribute to most errors. Matching dosing tools more closely with prescribed dose volumes, as well as using pictograms, can greatly reduce the number of pediatric medication errors, the researchers noted.

The study shows that 83.5% of parents made at least one dosing error (overdosing was present in 12.1% of errors), and 29.3% of parents made at least one large error in administering their children’s medicine. Parents who received text-only instructions or milliliter/teaspoon labels made more large errors. The biggest influence on errors resulted from providing tools more closely matched to the recommended dose measurements.

The researchers conducted a randomized controlled experiment in three pediatric clinics. Each site’s institutional review board approved the study. An average of 491 parents of children older than 8 years were randomly assigned to one of four groups, and given labels and dosing tools that varied in label instruction format and units. Each parent measured nine doses of liquid medicine in a random order, using three different tools.

Parents in group 1 received text and pictogram dosing instructions with milliliter-only labels and tools. They had decreased odds of making a dosing error compared with parents who received milliliter/teaspoon labels and tools without pictographic instructions in groups 2 and 4, and had lower odds of making large dosing errors compared with group 3, whose participants received text-only instructions (Pediatrics. 2017 June 27. doi: 10.1542/peds.2016-3237).

“Our findings support the use of a specific algorithm to help health care providers and pharmacists determine which dosing tool is most optimal to provide to parents,” said Dr. Yin. “We found that pictograms were associated with statistically significant reductions in large overdosing errors, with a trend for reduction in any error.”

No financial disclosures or conflicts of interest were reported.

[email protected]

In nine pediatric dosing trials, more than 80% of parents made more than one medication dosing error, according to a study by H. Shonna Yin, MD, and associates. Misunderstandings about how to accurately choose the right dosing tools as well as confusion related to units of measure contribute to most errors. Matching dosing tools more closely with prescribed dose volumes, as well as using pictograms, can greatly reduce the number of pediatric medication errors, the researchers noted.

The study shows that 83.5% of parents made at least one dosing error (overdosing was present in 12.1% of errors), and 29.3% of parents made at least one large error in administering their children’s medicine. Parents who received text-only instructions or milliliter/teaspoon labels made more large errors. The biggest influence on errors resulted from providing tools more closely matched to the recommended dose measurements.

The researchers conducted a randomized controlled experiment in three pediatric clinics. Each site’s institutional review board approved the study. An average of 491 parents of children older than 8 years were randomly assigned to one of four groups, and given labels and dosing tools that varied in label instruction format and units. Each parent measured nine doses of liquid medicine in a random order, using three different tools.

Parents in group 1 received text and pictogram dosing instructions with milliliter-only labels and tools. They had decreased odds of making a dosing error compared with parents who received milliliter/teaspoon labels and tools without pictographic instructions in groups 2 and 4, and had lower odds of making large dosing errors compared with group 3, whose participants received text-only instructions (Pediatrics. 2017 June 27. doi: 10.1542/peds.2016-3237).

“Our findings support the use of a specific algorithm to help health care providers and pharmacists determine which dosing tool is most optimal to provide to parents,” said Dr. Yin. “We found that pictograms were associated with statistically significant reductions in large overdosing errors, with a trend for reduction in any error.”

No financial disclosures or conflicts of interest were reported.

[email protected]

In nine pediatric dosing trials, more than 80% of parents made more than one medication dosing error, according to a study by H. Shonna Yin, MD, and associates. Misunderstandings about how to accurately choose the right dosing tools as well as confusion related to units of measure contribute to most errors. Matching dosing tools more closely with prescribed dose volumes, as well as using pictograms, can greatly reduce the number of pediatric medication errors, the researchers noted.

The study shows that 83.5% of parents made at least one dosing error (overdosing was present in 12.1% of errors), and 29.3% of parents made at least one large error in administering their children’s medicine. Parents who received text-only instructions or milliliter/teaspoon labels made more large errors. The biggest influence on errors resulted from providing tools more closely matched to the recommended dose measurements.

The researchers conducted a randomized controlled experiment in three pediatric clinics. Each site’s institutional review board approved the study. An average of 491 parents of children older than 8 years were randomly assigned to one of four groups, and given labels and dosing tools that varied in label instruction format and units. Each parent measured nine doses of liquid medicine in a random order, using three different tools.

Parents in group 1 received text and pictogram dosing instructions with milliliter-only labels and tools. They had decreased odds of making a dosing error compared with parents who received milliliter/teaspoon labels and tools without pictographic instructions in groups 2 and 4, and had lower odds of making large dosing errors compared with group 3, whose participants received text-only instructions (Pediatrics. 2017 June 27. doi: 10.1542/peds.2016-3237).

“Our findings support the use of a specific algorithm to help health care providers and pharmacists determine which dosing tool is most optimal to provide to parents,” said Dr. Yin. “We found that pictograms were associated with statistically significant reductions in large overdosing errors, with a trend for reduction in any error.”

No financial disclosures or conflicts of interest were reported.

[email protected]

LAS VEGAS – Serum matrix metalloproteinase-degraded C-reactive protein, or CRPM, may be the answer to two major unmet needs in the effort to develop the first disease-modifying treatments for osteoarthritis, Anne-Christine Bay-Jensen, PhD, said at the World Congress on Osteoarthritis.

[email protected]
 

LAS VEGAS – Serum matrix metalloproteinase-degraded C-reactive protein, or CRPM, may be the answer to two major unmet needs in the effort to develop the first disease-modifying treatments for osteoarthritis, Anne-Christine Bay-Jensen, PhD, said at the World Congress on Osteoarthritis.

[email protected]
 

LAS VEGAS – Serum matrix metalloproteinase-degraded C-reactive protein, or CRPM, may be the answer to two major unmet needs in the effort to develop the first disease-modifying treatments for osteoarthritis, Anne-Christine Bay-Jensen, PhD, said at the World Congress on Osteoarthritis.

[email protected]
 

The very-low-volume practice of surgeons performing no more than one open abdominal aortic aneurysm repair (OAR) or carotid endarterectomy (CEA) per year has persisted in New York State and was associated with worse postoperative outcomes and longer lengths of stay in a cohort study of statewide hospital data.

The study examined inpatient data on elective OARs and CEAs performed from 2000 to 2014 in every hospital in the state.

While the numbers and proportions of very-low-volume surgeons decreased (44.6%-23% for OAR and 35.2%-18.1% for CEA) and the number of procedures performed by these surgeons also decreased (QAR, 346-47; CEA, 395-90), the data are “concerning” and elucidate the “persistence” of very-low-volume practice in open vascular surgery, said Jialin Mao, MD, of Cornell University, New York, and associates (JAMA Surg. doi: 10:1001/jamasurg.2017.1100).

Very-low-volume surgeons were significantly less likely to be vascular surgeons, compared with higher-volume surgeons for both OAR (23.9% vs. 63.9%) and CEA (14.6% vs. 51.7%), they reported.

Compared with patients treated by higher-volume surgeons, those whose OAR was performed by very-low-volume surgeons had a twofold higher risk of postoperative death (6.7% vs. 3.5%) after adjusting for patient risk factors, surgeon specialty, and facility characteristics. Patients of very-low-volume surgeons also had significantly higher odds of sepsis or shock (odds ratio, 1.45), prolonged length of stay (OR, 1.37) and 30-day readmission (OR, 1.19), although the latter was not significant.

Similarly, patients whose CEA was performed by very-low-volume surgeons had a significant 1.8-fold higher odds of experiencing postoperative acute myocardial infarction (1.5% vs. 0.5%) and stroke (3.5% vs. 2.1%). They also were significantly more likely to have 30-day readmission (OR, 1.30).

With both procedures, patients treated by very-low-volume surgeons tended to be younger and healthier (less likely to have two or more comorbidities). They also were more likely to be nonwhite or insured by Medicaid.

“It is reasonable to speculate,” the researchers wrote, “that those treated by very-low-volume surgeons were more likely to be socioeconomically disadvantaged.”

Notably, 30% of the very-low-volume practice occurred in New York City, “where accessibility to high-volume practitioners should generally be higher,” they said.

The findings “indicate the need to eliminate this type of practice, to restrict the practice of these very-low-volume surgeons or to force referrals to higher-volume and specialized surgeons, and to improve disparity in access to high-quality care for all patients,” they said.

The study was funded in part by the U.S. Food and Drug Administration. The researchers reported having no relevant conflicts of interest.

The very-low-volume practice of surgeons performing no more than one open abdominal aortic aneurysm repair (OAR) or carotid endarterectomy (CEA) per year has persisted in New York State and was associated with worse postoperative outcomes and longer lengths of stay in a cohort study of statewide hospital data.

The study examined inpatient data on elective OARs and CEAs performed from 2000 to 2014 in every hospital in the state.

While the numbers and proportions of very-low-volume surgeons decreased (44.6%-23% for OAR and 35.2%-18.1% for CEA) and the number of procedures performed by these surgeons also decreased (QAR, 346-47; CEA, 395-90), the data are “concerning” and elucidate the “persistence” of very-low-volume practice in open vascular surgery, said Jialin Mao, MD, of Cornell University, New York, and associates (JAMA Surg. doi: 10:1001/jamasurg.2017.1100).

Very-low-volume surgeons were significantly less likely to be vascular surgeons, compared with higher-volume surgeons for both OAR (23.9% vs. 63.9%) and CEA (14.6% vs. 51.7%), they reported.

Compared with patients treated by higher-volume surgeons, those whose OAR was performed by very-low-volume surgeons had a twofold higher risk of postoperative death (6.7% vs. 3.5%) after adjusting for patient risk factors, surgeon specialty, and facility characteristics. Patients of very-low-volume surgeons also had significantly higher odds of sepsis or shock (odds ratio, 1.45), prolonged length of stay (OR, 1.37) and 30-day readmission (OR, 1.19), although the latter was not significant.

Similarly, patients whose CEA was performed by very-low-volume surgeons had a significant 1.8-fold higher odds of experiencing postoperative acute myocardial infarction (1.5% vs. 0.5%) and stroke (3.5% vs. 2.1%). They also were significantly more likely to have 30-day readmission (OR, 1.30).

With both procedures, patients treated by very-low-volume surgeons tended to be younger and healthier (less likely to have two or more comorbidities). They also were more likely to be nonwhite or insured by Medicaid.

“It is reasonable to speculate,” the researchers wrote, “that those treated by very-low-volume surgeons were more likely to be socioeconomically disadvantaged.”

Notably, 30% of the very-low-volume practice occurred in New York City, “where accessibility to high-volume practitioners should generally be higher,” they said.

The findings “indicate the need to eliminate this type of practice, to restrict the practice of these very-low-volume surgeons or to force referrals to higher-volume and specialized surgeons, and to improve disparity in access to high-quality care for all patients,” they said.

The study was funded in part by the U.S. Food and Drug Administration. The researchers reported having no relevant conflicts of interest.

The very-low-volume practice of surgeons performing no more than one open abdominal aortic aneurysm repair (OAR) or carotid endarterectomy (CEA) per year has persisted in New York State and was associated with worse postoperative outcomes and longer lengths of stay in a cohort study of statewide hospital data.

The study examined inpatient data on elective OARs and CEAs performed from 2000 to 2014 in every hospital in the state.

While the numbers and proportions of very-low-volume surgeons decreased (44.6%-23% for OAR and 35.2%-18.1% for CEA) and the number of procedures performed by these surgeons also decreased (QAR, 346-47; CEA, 395-90), the data are “concerning” and elucidate the “persistence” of very-low-volume practice in open vascular surgery, said Jialin Mao, MD, of Cornell University, New York, and associates (JAMA Surg. doi: 10:1001/jamasurg.2017.1100).

Very-low-volume surgeons were significantly less likely to be vascular surgeons, compared with higher-volume surgeons for both OAR (23.9% vs. 63.9%) and CEA (14.6% vs. 51.7%), they reported.

Compared with patients treated by higher-volume surgeons, those whose OAR was performed by very-low-volume surgeons had a twofold higher risk of postoperative death (6.7% vs. 3.5%) after adjusting for patient risk factors, surgeon specialty, and facility characteristics. Patients of very-low-volume surgeons also had significantly higher odds of sepsis or shock (odds ratio, 1.45), prolonged length of stay (OR, 1.37) and 30-day readmission (OR, 1.19), although the latter was not significant.

Similarly, patients whose CEA was performed by very-low-volume surgeons had a significant 1.8-fold higher odds of experiencing postoperative acute myocardial infarction (1.5% vs. 0.5%) and stroke (3.5% vs. 2.1%). They also were significantly more likely to have 30-day readmission (OR, 1.30).

With both procedures, patients treated by very-low-volume surgeons tended to be younger and healthier (less likely to have two or more comorbidities). They also were more likely to be nonwhite or insured by Medicaid.

“It is reasonable to speculate,” the researchers wrote, “that those treated by very-low-volume surgeons were more likely to be socioeconomically disadvantaged.”

Notably, 30% of the very-low-volume practice occurred in New York City, “where accessibility to high-volume practitioners should generally be higher,” they said.

The findings “indicate the need to eliminate this type of practice, to restrict the practice of these very-low-volume surgeons or to force referrals to higher-volume and specialized surgeons, and to improve disparity in access to high-quality care for all patients,” they said.

The study was funded in part by the U.S. Food and Drug Administration. The researchers reported having no relevant conflicts of interest.

NEW YORK – Repairing mitral valves in pediatric patients must overcome two issues: the wide variability in their anatomy and their growth. Using strategies and techniques common in adult mitral surgery can accomplish good mitral valve function in children, but some techniques in children differ, like using combined resorbable material with autologous tissue or transferring native chords instead of placing artificial chords to a malfunctioning leaflet.

Pedro del Nido, MD, of Boston Children’s Hospital, said the spectrum of mitral valve pathology in children goes from congenital mitral stenosis with a thick annulus with leaflet immobility to leaflet hypermobility that involves anterior leaflet prolapse and can involve a cleft that causes regurgitation. Dr. del Nido explained his surgical approaches for mitral valve disease in children at the 2017 Mitral Conclave, sponsored by the American Association of Thoracic Surgery.

NEW YORK – Repairing mitral valves in pediatric patients must overcome two issues: the wide variability in their anatomy and their growth. Using strategies and techniques common in adult mitral surgery can accomplish good mitral valve function in children, but some techniques in children differ, like using combined resorbable material with autologous tissue or transferring native chords instead of placing artificial chords to a malfunctioning leaflet.

Pedro del Nido, MD, of Boston Children’s Hospital, said the spectrum of mitral valve pathology in children goes from congenital mitral stenosis with a thick annulus with leaflet immobility to leaflet hypermobility that involves anterior leaflet prolapse and can involve a cleft that causes regurgitation. Dr. del Nido explained his surgical approaches for mitral valve disease in children at the 2017 Mitral Conclave, sponsored by the American Association of Thoracic Surgery.

NEW YORK – Repairing mitral valves in pediatric patients must overcome two issues: the wide variability in their anatomy and their growth. Using strategies and techniques common in adult mitral surgery can accomplish good mitral valve function in children, but some techniques in children differ, like using combined resorbable material with autologous tissue or transferring native chords instead of placing artificial chords to a malfunctioning leaflet.

Pedro del Nido, MD, of Boston Children’s Hospital, said the spectrum of mitral valve pathology in children goes from congenital mitral stenosis with a thick annulus with leaflet immobility to leaflet hypermobility that involves anterior leaflet prolapse and can involve a cleft that causes regurgitation. Dr. del Nido explained his surgical approaches for mitral valve disease in children at the 2017 Mitral Conclave, sponsored by the American Association of Thoracic Surgery.

CHICAGO – HER2-positive/HR-negative breast tumors may have a different biology than HER2+/HR+ tumors and may derive more benefit from dual HER2 blockade, according to 5-year results from the phase III ALTTO trial comparing 1 year of adjuvant anti-HER2 therapy with lapatinib and trastuzumab alone, sequentially, or in combination in patients with HER2-positive early breast cancer.

The hazard ratios for this preplanned updated analysis at a median of 6.9 years of follow-up (when all patients had reached 5 years of follow-up) are similar to those from the primary analysis reported at the 2014 ASCO annual meeting and published in the Journal of Clinical Oncology in 2015 (J Clin Oncol. 2015;34:1034-42) at a median clinical follow-up of 4.5 years, Alvaro Moreno-Aspitia, MD, reported at the annual meeting of the American Society of Clinical Oncology.

In the current analysis, the rate of disease-free survival was 85% with combined lapatinib and trastuzumab (L+T), 84% for sequential trastuzumab and lapatinib (T–L), and 82% with T (hazard ratio for disease-free survival was 0.86 for L+T vs. T and 0.93 for T–L vs. T alone,) said Dr. Moreno-Aspitia of Mayo Clinic, Jacksonville, Fla.

“So, at this time, as noted in the primary analysis, there’s no benefit on the primary endpoint in regard to dual HER2 blockade as provided in this clinical trial,” he said.

There also were no significant differences seen in disease-free survival based on chemotherapy timing, he said.

Notably, disease-free survival was similar across treatment groups among patients with HER2+/HR+ tumors (85% for L+T, 85% to T–L, and 83% for T; HRs, 0.91 and 0.90 vs. T, respectively), but, among those with HER2+/HR– tumors, the 6-year disease-free survival difference for L+T (84%) vs. T (80%) was slightly greater (HR, 0.80).

“This is a hypothesis generating observation that also holds that possibly these patients with hormone receptor–negative tumors may derive benefit from dual HER2 blockade,” Dr. Moreno-Aspitia said, noting that this has also been observed in several other trials.

The 6-year overall survival in ALTTO was 93%, 92%, and 91% for L+T, T–L, and T, respectively (HRs for overall survival, 0.86 for L+T vs. T and 0.88 for T–L).

“At this time, there is absolutely no [overall survival] benefit on dual HER2 blockade over single agent trastuzumab. However, it is very rewarding to see that over 90% of the patients who participated in this trial are alive at this longer-term follow-up,” he said.

As for cardiac events, the numbers remained low as in the primary ALTTO analysis, and no new safety signals had emerged.

ALTTO study subjects were 8,381 patients randomized from 946 sites in 44 countries between June 2007 and July 2011. Those in the L+T group received both agents together for 52 weeks; those in the sequential treatment group received T for 12 weeks followed by a 6-week wash-out period, followed by lapatinib for 34 weeks; and those in the trastuzumab arm (the control arm) and the lapatinib arm each received treatment for 52 weeks. In 2011 the lapatinib arm was closed because of futility, and results for that arm are not included in this analysis.

Long-term follow up of participants continues, a large number of correlative studies are ongoing, and final results will be reported when all patients have been followed for at least 10 years, Dr. Moreno-Aspitia said.

The ALTTO trial was sponsored by GlaxoSmithKline and Novartis. Dr. Moreno-Aspitia reported having no disclosures.

[email protected]

CHICAGO – HER2-positive/HR-negative breast tumors may have a different biology than HER2+/HR+ tumors and may derive more benefit from dual HER2 blockade, according to 5-year results from the phase III ALTTO trial comparing 1 year of adjuvant anti-HER2 therapy with lapatinib and trastuzumab alone, sequentially, or in combination in patients with HER2-positive early breast cancer.

The hazard ratios for this preplanned updated analysis at a median of 6.9 years of follow-up (when all patients had reached 5 years of follow-up) are similar to those from the primary analysis reported at the 2014 ASCO annual meeting and published in the Journal of Clinical Oncology in 2015 (J Clin Oncol. 2015;34:1034-42) at a median clinical follow-up of 4.5 years, Alvaro Moreno-Aspitia, MD, reported at the annual meeting of the American Society of Clinical Oncology.

In the current analysis, the rate of disease-free survival was 85% with combined lapatinib and trastuzumab (L+T), 84% for sequential trastuzumab and lapatinib (T–L), and 82% with T (hazard ratio for disease-free survival was 0.86 for L+T vs. T and 0.93 for T–L vs. T alone,) said Dr. Moreno-Aspitia of Mayo Clinic, Jacksonville, Fla.

“So, at this time, as noted in the primary analysis, there’s no benefit on the primary endpoint in regard to dual HER2 blockade as provided in this clinical trial,” he said.

There also were no significant differences seen in disease-free survival based on chemotherapy timing, he said.

Notably, disease-free survival was similar across treatment groups among patients with HER2+/HR+ tumors (85% for L+T, 85% to T–L, and 83% for T; HRs, 0.91 and 0.90 vs. T, respectively), but, among those with HER2+/HR– tumors, the 6-year disease-free survival difference for L+T (84%) vs. T (80%) was slightly greater (HR, 0.80).

“This is a hypothesis generating observation that also holds that possibly these patients with hormone receptor–negative tumors may derive benefit from dual HER2 blockade,” Dr. Moreno-Aspitia said, noting that this has also been observed in several other trials.

The 6-year overall survival in ALTTO was 93%, 92%, and 91% for L+T, T–L, and T, respectively (HRs for overall survival, 0.86 for L+T vs. T and 0.88 for T–L).

“At this time, there is absolutely no [overall survival] benefit on dual HER2 blockade over single agent trastuzumab. However, it is very rewarding to see that over 90% of the patients who participated in this trial are alive at this longer-term follow-up,” he said.

As for cardiac events, the numbers remained low as in the primary ALTTO analysis, and no new safety signals had emerged.

ALTTO study subjects were 8,381 patients randomized from 946 sites in 44 countries between June 2007 and July 2011. Those in the L+T group received both agents together for 52 weeks; those in the sequential treatment group received T for 12 weeks followed by a 6-week wash-out period, followed by lapatinib for 34 weeks; and those in the trastuzumab arm (the control arm) and the lapatinib arm each received treatment for 52 weeks. In 2011 the lapatinib arm was closed because of futility, and results for that arm are not included in this analysis.

Long-term follow up of participants continues, a large number of correlative studies are ongoing, and final results will be reported when all patients have been followed for at least 10 years, Dr. Moreno-Aspitia said.

The ALTTO trial was sponsored by GlaxoSmithKline and Novartis. Dr. Moreno-Aspitia reported having no disclosures.

[email protected]

CHICAGO – HER2-positive/HR-negative breast tumors may have a different biology than HER2+/HR+ tumors and may derive more benefit from dual HER2 blockade, according to 5-year results from the phase III ALTTO trial comparing 1 year of adjuvant anti-HER2 therapy with lapatinib and trastuzumab alone, sequentially, or in combination in patients with HER2-positive early breast cancer.

The hazard ratios for this preplanned updated analysis at a median of 6.9 years of follow-up (when all patients had reached 5 years of follow-up) are similar to those from the primary analysis reported at the 2014 ASCO annual meeting and published in the Journal of Clinical Oncology in 2015 (J Clin Oncol. 2015;34:1034-42) at a median clinical follow-up of 4.5 years, Alvaro Moreno-Aspitia, MD, reported at the annual meeting of the American Society of Clinical Oncology.

In the current analysis, the rate of disease-free survival was 85% with combined lapatinib and trastuzumab (L+T), 84% for sequential trastuzumab and lapatinib (T–L), and 82% with T (hazard ratio for disease-free survival was 0.86 for L+T vs. T and 0.93 for T–L vs. T alone,) said Dr. Moreno-Aspitia of Mayo Clinic, Jacksonville, Fla.

“So, at this time, as noted in the primary analysis, there’s no benefit on the primary endpoint in regard to dual HER2 blockade as provided in this clinical trial,” he said.

There also were no significant differences seen in disease-free survival based on chemotherapy timing, he said.

Notably, disease-free survival was similar across treatment groups among patients with HER2+/HR+ tumors (85% for L+T, 85% to T–L, and 83% for T; HRs, 0.91 and 0.90 vs. T, respectively), but, among those with HER2+/HR– tumors, the 6-year disease-free survival difference for L+T (84%) vs. T (80%) was slightly greater (HR, 0.80).

“This is a hypothesis generating observation that also holds that possibly these patients with hormone receptor–negative tumors may derive benefit from dual HER2 blockade,” Dr. Moreno-Aspitia said, noting that this has also been observed in several other trials.

The 6-year overall survival in ALTTO was 93%, 92%, and 91% for L+T, T–L, and T, respectively (HRs for overall survival, 0.86 for L+T vs. T and 0.88 for T–L).

“At this time, there is absolutely no [overall survival] benefit on dual HER2 blockade over single agent trastuzumab. However, it is very rewarding to see that over 90% of the patients who participated in this trial are alive at this longer-term follow-up,” he said.

As for cardiac events, the numbers remained low as in the primary ALTTO analysis, and no new safety signals had emerged.

ALTTO study subjects were 8,381 patients randomized from 946 sites in 44 countries between June 2007 and July 2011. Those in the L+T group received both agents together for 52 weeks; those in the sequential treatment group received T for 12 weeks followed by a 6-week wash-out period, followed by lapatinib for 34 weeks; and those in the trastuzumab arm (the control arm) and the lapatinib arm each received treatment for 52 weeks. In 2011 the lapatinib arm was closed because of futility, and results for that arm are not included in this analysis.

Long-term follow up of participants continues, a large number of correlative studies are ongoing, and final results will be reported when all patients have been followed for at least 10 years, Dr. Moreno-Aspitia said.

The ALTTO trial was sponsored by GlaxoSmithKline and Novartis. Dr. Moreno-Aspitia reported having no disclosures.

[email protected]

New Epilepsy Classification System

A patient’s epilepsy syndrome is the most important factor when choosing an AED, Dr. French said. According to a new epilepsy classification system published by the International League Against Epilepsy, generalized epilepsy may be further categorized as absence, myoclonic, atonic, tonic, and tonic–clonic. Focal epilepsy (formerly called partial epilepsy) may be categorized as focal aware (formerly simple partial), focal impaired awareness (formerly complex partial), and focal to bilateral tonic–clonic (formerly secondary generalized).

Combined generalized and focal epilepsy is a new category associated with epileptic encephalopathies, such as Dravet syndrome and Lennox-Gastaut syndrome. Finally, “seizures of unknown onset” describes cases where the clinician does not have enough information to determine whether the epilepsy is focal or generalized.

Narrow-spectrum drugs, including carbamazepine, oxcarbazepine, tiagabine, gabapentin, and pregabalin, should only be used in patients with focal epilepsy. “Narrow-spectrum drugs might make generalized seizures worse, or they fail to treat generalized seizures,” Dr. French said. “People with generalized epilepsy, generalized and focal epilepsy combined, or epilepsy of unknown onset should be on broad-spectrum agents—valproic acid, topiramate, lamotrigine, levetiracetam, zonisamide, and perampanel.”

Risk of Adverse Effects

“With any AED, the most common adverse events are dose-related,” Dr. French said. Some adverse events occur during titration and eventually resolve. Some drugs are associated with specific adverse events and therefore should be avoided in certain patient populations.

For instance, carbamazepine, oxcarbazepine, and eslicarbazepine may cause hyponatremia and should be given with caution to at-risk patients, such as the elderly. Likewise, drugs that may cause renal calculi, such as topiramate and zonisamide, should be given with caution to patients with that condition. Enzyme-inducing AEDs that increase cholesterol levels (eg, carbamazepine and phenytoin) should be avoided in patients with cardiovascular risk factors. For patients with weight problems or eating disorders, physicians should bear in mind that valproate, gabapentin, carbamazepine, pregabalin, ezogabine, and perampanel have been known to increase weight, while topiramate, zonisamide, and felbamate have been known to decrease weight.

AEDs that may worsen psychiatric function include levetiracetam, topiramate, zonisamide, tiagabine, phenobarbital, and perampanel. “Make sure that you ask patients when they are on levetiracetam whether they are experiencing increased irritability, although not everyone recognizes their mood changes,” Dr. French said. “Sometimes the spouse will complain, but the person will not.” On the other hand, carbamazepine, valproic acid, lamotrigine, and pregabalin have a tendency to improve psychiatric function—but not always. Psychiatric function “can go either way” with any of the AEDs, she said.

Some patients experience adverse drug effects as a result of add-on therapy. In some cases, a pharmacodynamic interaction between the new and old drugs may be responsible. Removing the add-on drug or the background drug may help. “Sometimes it is a better idea to take away the background drugs,” she said.

Older AEDs—carbamazepine, phenytoin, phenobarbital, and valproic acid—are associated with idiosyncratic adverse effects, including serious rash, liver failure, bone marrow failure, and pancreatitis. While some of the newer drugs also have such risks, the overall rate of idiosyncratic adverse reactions with their use is lower. Thus far, levetiracetam, brivaracetam, gabapentin, and pregabalin have not been associated with major idiosyncratic adverse effects, Dr. French noted.

Drug Initiation and Interactions

“The ability to initiate a drug rapidly is sometimes the driving characteristic that causes some doctors to pick one drug over another,” Dr. French said. Drugs that can be initiated at a therapeutic dose in a single day include phenytoin, levetiracetam, valproic acid, gabapentin, pregabalin, lacosamide, and brivaracetam. Other AEDs, such as carbamazepine, lamotrigine, perampanel, and oxcarbazepine, require gradual initiation over one to 10 weeks. Some drugs that take longer to initiate may be better tolerated overall, she said.

Generally, older AEDs are more likely to cause drug interactions, compared with newer drugs. Phenytoin, phenobarbital, and carbamazepine are enzyme inducers, which may cause problems for patients who are on statins. Valproic acid is a hepatic enzyme inhibitor, and phenytoin and valproic acid can have protein-binding interactions. Oral contraceptives reduce lamotrigine’s efficacy by doubling the clearance of the AED, Dr. French explained. “This can be problematic when women do not tell you when they are going on and off the contraceptive pill. They can have a breakthrough seizure, and it is only after the fact that you realize why that happened,” she said.

Interactions between oral contraceptive are common with other AEDs, as well. She cited a recent retrospective study involving 1,144 women with epilepsy ages 18 to 47 who provided demographic, epilepsy, AED, contraceptive, and pregnancy data. Survey results showed that 65% of their pregnancies were unintended. Oral forms of contraception had greater failure rates than nonoral forms, with intrauterine devices having the lowest failure rate.

—Adriene Marshall

Suggested Reading

Herzog AG, Mandle HB, Cahill KE, et al. Predictors of unintended pregnancy in women with epilepsy. Neurology. 2017;88(8):728-733.

Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512-521.

New Epilepsy Classification System

A patient’s epilepsy syndrome is the most important factor when choosing an AED, Dr. French said. According to a new epilepsy classification system published by the International League Against Epilepsy, generalized epilepsy may be further categorized as absence, myoclonic, atonic, tonic, and tonic–clonic. Focal epilepsy (formerly called partial epilepsy) may be categorized as focal aware (formerly simple partial), focal impaired awareness (formerly complex partial), and focal to bilateral tonic–clonic (formerly secondary generalized).

Combined generalized and focal epilepsy is a new category associated with epileptic encephalopathies, such as Dravet syndrome and Lennox-Gastaut syndrome. Finally, “seizures of unknown onset” describes cases where the clinician does not have enough information to determine whether the epilepsy is focal or generalized.

Narrow-spectrum drugs, including carbamazepine, oxcarbazepine, tiagabine, gabapentin, and pregabalin, should only be used in patients with focal epilepsy. “Narrow-spectrum drugs might make generalized seizures worse, or they fail to treat generalized seizures,” Dr. French said. “People with generalized epilepsy, generalized and focal epilepsy combined, or epilepsy of unknown onset should be on broad-spectrum agents—valproic acid, topiramate, lamotrigine, levetiracetam, zonisamide, and perampanel.”

Risk of Adverse Effects

“With any AED, the most common adverse events are dose-related,” Dr. French said. Some adverse events occur during titration and eventually resolve. Some drugs are associated with specific adverse events and therefore should be avoided in certain patient populations.

For instance, carbamazepine, oxcarbazepine, and eslicarbazepine may cause hyponatremia and should be given with caution to at-risk patients, such as the elderly. Likewise, drugs that may cause renal calculi, such as topiramate and zonisamide, should be given with caution to patients with that condition. Enzyme-inducing AEDs that increase cholesterol levels (eg, carbamazepine and phenytoin) should be avoided in patients with cardiovascular risk factors. For patients with weight problems or eating disorders, physicians should bear in mind that valproate, gabapentin, carbamazepine, pregabalin, ezogabine, and perampanel have been known to increase weight, while topiramate, zonisamide, and felbamate have been known to decrease weight.

AEDs that may worsen psychiatric function include levetiracetam, topiramate, zonisamide, tiagabine, phenobarbital, and perampanel. “Make sure that you ask patients when they are on levetiracetam whether they are experiencing increased irritability, although not everyone recognizes their mood changes,” Dr. French said. “Sometimes the spouse will complain, but the person will not.” On the other hand, carbamazepine, valproic acid, lamotrigine, and pregabalin have a tendency to improve psychiatric function—but not always. Psychiatric function “can go either way” with any of the AEDs, she said.

Some patients experience adverse drug effects as a result of add-on therapy. In some cases, a pharmacodynamic interaction between the new and old drugs may be responsible. Removing the add-on drug or the background drug may help. “Sometimes it is a better idea to take away the background drugs,” she said.

Older AEDs—carbamazepine, phenytoin, phenobarbital, and valproic acid—are associated with idiosyncratic adverse effects, including serious rash, liver failure, bone marrow failure, and pancreatitis. While some of the newer drugs also have such risks, the overall rate of idiosyncratic adverse reactions with their use is lower. Thus far, levetiracetam, brivaracetam, gabapentin, and pregabalin have not been associated with major idiosyncratic adverse effects, Dr. French noted.

Drug Initiation and Interactions

“The ability to initiate a drug rapidly is sometimes the driving characteristic that causes some doctors to pick one drug over another,” Dr. French said. Drugs that can be initiated at a therapeutic dose in a single day include phenytoin, levetiracetam, valproic acid, gabapentin, pregabalin, lacosamide, and brivaracetam. Other AEDs, such as carbamazepine, lamotrigine, perampanel, and oxcarbazepine, require gradual initiation over one to 10 weeks. Some drugs that take longer to initiate may be better tolerated overall, she said.

Generally, older AEDs are more likely to cause drug interactions, compared with newer drugs. Phenytoin, phenobarbital, and carbamazepine are enzyme inducers, which may cause problems for patients who are on statins. Valproic acid is a hepatic enzyme inhibitor, and phenytoin and valproic acid can have protein-binding interactions. Oral contraceptives reduce lamotrigine’s efficacy by doubling the clearance of the AED, Dr. French explained. “This can be problematic when women do not tell you when they are going on and off the contraceptive pill. They can have a breakthrough seizure, and it is only after the fact that you realize why that happened,” she said.

Interactions between oral contraceptive are common with other AEDs, as well. She cited a recent retrospective study involving 1,144 women with epilepsy ages 18 to 47 who provided demographic, epilepsy, AED, contraceptive, and pregnancy data. Survey results showed that 65% of their pregnancies were unintended. Oral forms of contraception had greater failure rates than nonoral forms, with intrauterine devices having the lowest failure rate.

—Adriene Marshall

Suggested Reading

Herzog AG, Mandle HB, Cahill KE, et al. Predictors of unintended pregnancy in women with epilepsy. Neurology. 2017;88(8):728-733.

Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512-521.

New Epilepsy Classification System

A patient’s epilepsy syndrome is the most important factor when choosing an AED, Dr. French said. According to a new epilepsy classification system published by the International League Against Epilepsy, generalized epilepsy may be further categorized as absence, myoclonic, atonic, tonic, and tonic–clonic. Focal epilepsy (formerly called partial epilepsy) may be categorized as focal aware (formerly simple partial), focal impaired awareness (formerly complex partial), and focal to bilateral tonic–clonic (formerly secondary generalized).

Combined generalized and focal epilepsy is a new category associated with epileptic encephalopathies, such as Dravet syndrome and Lennox-Gastaut syndrome. Finally, “seizures of unknown onset” describes cases where the clinician does not have enough information to determine whether the epilepsy is focal or generalized.

Narrow-spectrum drugs, including carbamazepine, oxcarbazepine, tiagabine, gabapentin, and pregabalin, should only be used in patients with focal epilepsy. “Narrow-spectrum drugs might make generalized seizures worse, or they fail to treat generalized seizures,” Dr. French said. “People with generalized epilepsy, generalized and focal epilepsy combined, or epilepsy of unknown onset should be on broad-spectrum agents—valproic acid, topiramate, lamotrigine, levetiracetam, zonisamide, and perampanel.”

Risk of Adverse Effects

“With any AED, the most common adverse events are dose-related,” Dr. French said. Some adverse events occur during titration and eventually resolve. Some drugs are associated with specific adverse events and therefore should be avoided in certain patient populations.

For instance, carbamazepine, oxcarbazepine, and eslicarbazepine may cause hyponatremia and should be given with caution to at-risk patients, such as the elderly. Likewise, drugs that may cause renal calculi, such as topiramate and zonisamide, should be given with caution to patients with that condition. Enzyme-inducing AEDs that increase cholesterol levels (eg, carbamazepine and phenytoin) should be avoided in patients with cardiovascular risk factors. For patients with weight problems or eating disorders, physicians should bear in mind that valproate, gabapentin, carbamazepine, pregabalin, ezogabine, and perampanel have been known to increase weight, while topiramate, zonisamide, and felbamate have been known to decrease weight.

AEDs that may worsen psychiatric function include levetiracetam, topiramate, zonisamide, tiagabine, phenobarbital, and perampanel. “Make sure that you ask patients when they are on levetiracetam whether they are experiencing increased irritability, although not everyone recognizes their mood changes,” Dr. French said. “Sometimes the spouse will complain, but the person will not.” On the other hand, carbamazepine, valproic acid, lamotrigine, and pregabalin have a tendency to improve psychiatric function—but not always. Psychiatric function “can go either way” with any of the AEDs, she said.

Some patients experience adverse drug effects as a result of add-on therapy. In some cases, a pharmacodynamic interaction between the new and old drugs may be responsible. Removing the add-on drug or the background drug may help. “Sometimes it is a better idea to take away the background drugs,” she said.

Older AEDs—carbamazepine, phenytoin, phenobarbital, and valproic acid—are associated with idiosyncratic adverse effects, including serious rash, liver failure, bone marrow failure, and pancreatitis. While some of the newer drugs also have such risks, the overall rate of idiosyncratic adverse reactions with their use is lower. Thus far, levetiracetam, brivaracetam, gabapentin, and pregabalin have not been associated with major idiosyncratic adverse effects, Dr. French noted.

Drug Initiation and Interactions

“The ability to initiate a drug rapidly is sometimes the driving characteristic that causes some doctors to pick one drug over another,” Dr. French said. Drugs that can be initiated at a therapeutic dose in a single day include phenytoin, levetiracetam, valproic acid, gabapentin, pregabalin, lacosamide, and brivaracetam. Other AEDs, such as carbamazepine, lamotrigine, perampanel, and oxcarbazepine, require gradual initiation over one to 10 weeks. Some drugs that take longer to initiate may be better tolerated overall, she said.

Generally, older AEDs are more likely to cause drug interactions, compared with newer drugs. Phenytoin, phenobarbital, and carbamazepine are enzyme inducers, which may cause problems for patients who are on statins. Valproic acid is a hepatic enzyme inhibitor, and phenytoin and valproic acid can have protein-binding interactions. Oral contraceptives reduce lamotrigine’s efficacy by doubling the clearance of the AED, Dr. French explained. “This can be problematic when women do not tell you when they are going on and off the contraceptive pill. They can have a breakthrough seizure, and it is only after the fact that you realize why that happened,” she said.

Interactions between oral contraceptive are common with other AEDs, as well. She cited a recent retrospective study involving 1,144 women with epilepsy ages 18 to 47 who provided demographic, epilepsy, AED, contraceptive, and pregnancy data. Survey results showed that 65% of their pregnancies were unintended. Oral forms of contraception had greater failure rates than nonoral forms, with intrauterine devices having the lowest failure rate.

—Adriene Marshall

Suggested Reading

Herzog AG, Mandle HB, Cahill KE, et al. Predictors of unintended pregnancy in women with epilepsy. Neurology. 2017;88(8):728-733.

Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512-521.

Device Helps Patients Move Paralyzed Hands After Stroke

Patients with stroke who learn to use their minds to open and close a device fitted over their paralyzed hands gain some control over their hands, according to a study published online ahead of print May 26 in Stroke. Ten survivors of chronic hemiparetic stroke with moderate-to-severe upper-limb motor impairment used a powered exoskeleton that opened and closed the affected hand using spectral power from EEG signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. At 12 weeks, participants had a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in brain–computer interface control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved.

Bundy DT, Souders L, Baranyai K, et al. Contralesional brain-computer interface control of a powered exoskeleton for motor recovery in chronic stroke survivors. Stroke. 2017 May 26 [Epub ahead of print].

Pyrimethamine Lowers Levels of ALS Biomarker

Pyrimethamine is safe and well tolerated in amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print May 8 in Annals of Neurology. Participants underwent a multicenter, open-label, nine-month dose-ranging study to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in patients with SOD1 mutations linked to familial ALS. The study included 32 patients with various SOD1 genetic mutations linked to ALS. Participants had three lumbar punctures, blood studies, and a clinical assessment of strength, motor function, quality of life, and potential adverse effects. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit six, with a mean reduction of 13.5%, and at visit nine, with a mean reduction of 10.5%.

Lange DJ, Shahbazi M, Silani V, et al. Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations. Ann Neurol. 2017 May 8 [Epub ahead of print].

Statin Use Linked to Higher Risk of Parkinson’s Disease

Statins, especially lipophilic statins, are associated with higher risk of Parkinson’s disease, according to a study published in the June issue of Movement Disorders. The association is stronger with initial use, which suggests a facilitating effect, said the investigators. Researchers performed a retrospective case–control analysis and identified 2,322 people with incident Parkinson’s disease who had been enrolled in a claims database for at least 2.5 years before diagnosis or prescription of antiparkinson medication. They matched the cases with 2,322 controls by age, gender, and a follow-up window. Statin use was significantly associated with Parkinson’s disease risk. The strongest associations were for lipophilic statins (odds ratio [OR], 1.58) versus hydrophilic statins (OR, 1.19), statins plus nonstatins (OR, 1.95), and for the initial period after starting statins.

Liu G, Sterling NW, Kong L, et al. Statins may facilitate Parkinson’s disease: insight gained from a large, national claims database. Mov Disord. 2017;32(6):913-917.

Is Moderate Drinking Associated With Cognitive Decline?

Moderate alcohol consumption is associated with adverse brain outcomes, including hippocampal atrophy, according to a study published online ahead of print June 6 in BMJ. The study included 550 men and women with a mean age of 43 at study baseline. No patient had alcohol dependence, and all underwent brain MRI at follow-up. Higher alcohol consumption over the 30-year follow-up was associated with increased odds of hippocampal atrophy in a dose-dependent fashion. People consuming more than 30 units/week of alcohol were at the highest risk, compared with abstainers. People who drank moderately had three times the odds of right-sided hippocampal atrophy. There was no protective effect of light drinking over abstinence. Higher alcohol use also was associated with differences in corpus callosum microstructure and faster decline in lexical fluency.

Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017 Jun 6 [Epub ahead of print].

Consuming Low-Fat Dairy May Increase Risk for Parkinson’s Disease

Frequently consuming low-fat dairy products may be associated with an increased risk of Parkinson’s disease, according to a study published online ahead of print June 8 in Neurology. This study is based on data from 80,736 participants in the Nurses’ Health Study and 48,610 participants in the Health Professionals Follow-Up Study, with 26 and 24 years of follow-up, respectively. Both US-based studies were conducted through mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Total dairy intake was not significantly associated with Parkinson’s disease risk, but intake of low-fat dairy foods was associated with Parkinson’s disease risk. This association appeared to result from an increased risk of Parkinson’s disease associated with skim and low-fat milk.

Hughes KC, Gao X, Kim IY, et al. Intake of dairy foods and risk of Parkinson disease. Neurology. 2017 Jun 8 [Epub ahead of print].

Elevated Brain Amyloid Increases Likelihood of Cognitive Decline

Elevated baseline brain amyloid level, compared with normal brain amyloid level, is associated with higher likelihood of cognitive decline, according to a study published June 13 in JAMA. Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal people. Participants were classified at baseline as having normal or elevated brain amyloid using PET amyloid imaging or a CSF assay of amyloid β. Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC), Mini-Mental State Examination (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-SOB), and Logical Memory Delayed Recall. Compared with the group with normal amyloid, people with elevated amyloid had worse mean scores at four years on the PACC, MMSE, and CDR-SOB. For Logical Memory Delayed Recall, between-group scores were not significantly different at four years.

Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317(22):2305-2316.

Seven Risk Genes for Insomnia Found

Researchers have found seven risk genes for insomnia, according to a study published online ahead of print June 12 in Nature Genetics. To identify genetic factors for insomnia complaints, investigators performed a genome-wide association study and a genome-wide gene-based association study in 113,006 participants. The authors identified three loci and seven genes, including MEIS1, associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample. Sex-specific analyses suggest that the sexes have different genetic architectures, in addition to shared genetic factors. The researchers also found a substantial positive genetic correlation between insomnia complaints and internalizing personality traits and metabolic traits. There was a negative correlation with subjective well-being and educational attainment.

Hammerschlag AR, Stringer S, de Leeuw CA, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet. 2017 Jun 12 [Epub ahead of print].

Is Telemedicine for Headache as Effective as In-Person Visit?

In people with headache, a video consultation with a neurologist for treatment may be as effective as an in-person visit, according to a study published online ahead of print June 14 in Neurology. Researchers randomized, allocated, and consulted patients with nonacute headache via telemedicine or in a traditional manner in a noninferiority trial. Efficacy end points assessed by questionnaires at three and 12 months included change from baseline in Headache Impact Test-6 (HIT-6) and pain intensity. The primary safety end point was presence of secondary headache within 12 months after consultation. There were no differences between telemedicine and traditional consultations in HIT-6 or pain intensity over three periods. The absolute difference in HIT-6 from baseline was 0.3 at three months and 0.2 at 12 months.

Müller KI, Alstadhaug KB, Bekkelund SI. A randomized trial of telemedicine efficacy and safety for nonacute headaches. Neurology. 2017 Jun 14 [Epub ahead of print].

Minocycline Reduces Risk of Conversion From CIS to MS

The risk of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) is significantly lower with minocycline than with placebo over six months, but not over 24 months, according to a study published June 1 in the New England Journal of Medicine. This study included 142 participants who had had their first demyelinating symptoms within the previous 180 days. At 12 Canadian MS clinics, researchers randomly assigned participants to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of MS was established or until 24 months after randomization. The unadjusted risk of conversion to MS within six months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group.

Metz LM, Li DKB, Traboulsee AL, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med. 2017;376(22):2122-2133.

Can Gene Mutation Speed Memory Loss in Alzheimer’s Disease?

In a middle-aged cohort with Alzheimer’s disease risk, the BDNF Met allele is associated with steeper decline in episodic memory and executive function, according to a study published online ahead of print May 3 in Neurology. One thousand twenty-three adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention underwent BDNF genotyping and cognitive assessment at as many as five time points. A subset of participants underwent Pittsburgh compound B scanning. Compared with BDNF Val/Val homozygotes, Met carriers had steeper decline in verbal learning and memory, and in speed and flexibility. In addition, amyloid β burden moderated the relationship between BDNF and verbal learning and memory, such that Met carriers with greater amyloid β burden showed even steeper cognitive decline.

Boots EA, Schultz SA, Clark LR, et al. BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer’s Prevention. Neurology. 2017 May 3 [Epub ahead of print].

Support From Children Reduces Risk of Dementia

Positive social support from children is associated with reduced risk of dementia, whereas negative social support from children and other immediate family increases the risk, according to a study published in the Journal of Alzheimer’s Disease. Researchers analyzed 10-year follow-up data in 10,055 cognitively normal participants age 50 and older from the English Longitudinal Study of Aging. Incidence of dementia was identified from participant- or informant-reported physician diagnosed dementia or overall score of informant-completed IQCODE questionnaire. Positive social support from children significantly reduced the risk of dementia (hazard ratio, 0.83). Negative support from family and friends was significantly associated with increased risk of dementia. The causal mechanisms that create these associations require further research, said the researchers.

Khondoker M, Rafnsson SB, Morris S, et al. Positive and negative experiences of social support and risk of dementia in later life: an investigation using the English Longitudinal Study of Ageing. J Alzheimers Dis. 2017;58(1):99-108.

—Kimberly Williams

Device Helps Patients Move Paralyzed Hands After Stroke

Patients with stroke who learn to use their minds to open and close a device fitted over their paralyzed hands gain some control over their hands, according to a study published online ahead of print May 26 in Stroke. Ten survivors of chronic hemiparetic stroke with moderate-to-severe upper-limb motor impairment used a powered exoskeleton that opened and closed the affected hand using spectral power from EEG signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. At 12 weeks, participants had a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in brain–computer interface control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved.

Bundy DT, Souders L, Baranyai K, et al. Contralesional brain-computer interface control of a powered exoskeleton for motor recovery in chronic stroke survivors. Stroke. 2017 May 26 [Epub ahead of print].

Pyrimethamine Lowers Levels of ALS Biomarker

Pyrimethamine is safe and well tolerated in amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print May 8 in Annals of Neurology. Participants underwent a multicenter, open-label, nine-month dose-ranging study to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in patients with SOD1 mutations linked to familial ALS. The study included 32 patients with various SOD1 genetic mutations linked to ALS. Participants had three lumbar punctures, blood studies, and a clinical assessment of strength, motor function, quality of life, and potential adverse effects. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit six, with a mean reduction of 13.5%, and at visit nine, with a mean reduction of 10.5%.

Lange DJ, Shahbazi M, Silani V, et al. Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations. Ann Neurol. 2017 May 8 [Epub ahead of print].

Statin Use Linked to Higher Risk of Parkinson’s Disease

Statins, especially lipophilic statins, are associated with higher risk of Parkinson’s disease, according to a study published in the June issue of Movement Disorders. The association is stronger with initial use, which suggests a facilitating effect, said the investigators. Researchers performed a retrospective case–control analysis and identified 2,322 people with incident Parkinson’s disease who had been enrolled in a claims database for at least 2.5 years before diagnosis or prescription of antiparkinson medication. They matched the cases with 2,322 controls by age, gender, and a follow-up window. Statin use was significantly associated with Parkinson’s disease risk. The strongest associations were for lipophilic statins (odds ratio [OR], 1.58) versus hydrophilic statins (OR, 1.19), statins plus nonstatins (OR, 1.95), and for the initial period after starting statins.

Liu G, Sterling NW, Kong L, et al. Statins may facilitate Parkinson’s disease: insight gained from a large, national claims database. Mov Disord. 2017;32(6):913-917.

Is Moderate Drinking Associated With Cognitive Decline?

Moderate alcohol consumption is associated with adverse brain outcomes, including hippocampal atrophy, according to a study published online ahead of print June 6 in BMJ. The study included 550 men and women with a mean age of 43 at study baseline. No patient had alcohol dependence, and all underwent brain MRI at follow-up. Higher alcohol consumption over the 30-year follow-up was associated with increased odds of hippocampal atrophy in a dose-dependent fashion. People consuming more than 30 units/week of alcohol were at the highest risk, compared with abstainers. People who drank moderately had three times the odds of right-sided hippocampal atrophy. There was no protective effect of light drinking over abstinence. Higher alcohol use also was associated with differences in corpus callosum microstructure and faster decline in lexical fluency.

Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017 Jun 6 [Epub ahead of print].

Consuming Low-Fat Dairy May Increase Risk for Parkinson’s Disease

Frequently consuming low-fat dairy products may be associated with an increased risk of Parkinson’s disease, according to a study published online ahead of print June 8 in Neurology. This study is based on data from 80,736 participants in the Nurses’ Health Study and 48,610 participants in the Health Professionals Follow-Up Study, with 26 and 24 years of follow-up, respectively. Both US-based studies were conducted through mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Total dairy intake was not significantly associated with Parkinson’s disease risk, but intake of low-fat dairy foods was associated with Parkinson’s disease risk. This association appeared to result from an increased risk of Parkinson’s disease associated with skim and low-fat milk.

Hughes KC, Gao X, Kim IY, et al. Intake of dairy foods and risk of Parkinson disease. Neurology. 2017 Jun 8 [Epub ahead of print].

Elevated Brain Amyloid Increases Likelihood of Cognitive Decline

Elevated baseline brain amyloid level, compared with normal brain amyloid level, is associated with higher likelihood of cognitive decline, according to a study published June 13 in JAMA. Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal people. Participants were classified at baseline as having normal or elevated brain amyloid using PET amyloid imaging or a CSF assay of amyloid β. Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC), Mini-Mental State Examination (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-SOB), and Logical Memory Delayed Recall. Compared with the group with normal amyloid, people with elevated amyloid had worse mean scores at four years on the PACC, MMSE, and CDR-SOB. For Logical Memory Delayed Recall, between-group scores were not significantly different at four years.

Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317(22):2305-2316.

Seven Risk Genes for Insomnia Found

Researchers have found seven risk genes for insomnia, according to a study published online ahead of print June 12 in Nature Genetics. To identify genetic factors for insomnia complaints, investigators performed a genome-wide association study and a genome-wide gene-based association study in 113,006 participants. The authors identified three loci and seven genes, including MEIS1, associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample. Sex-specific analyses suggest that the sexes have different genetic architectures, in addition to shared genetic factors. The researchers also found a substantial positive genetic correlation between insomnia complaints and internalizing personality traits and metabolic traits. There was a negative correlation with subjective well-being and educational attainment.

Hammerschlag AR, Stringer S, de Leeuw CA, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet. 2017 Jun 12 [Epub ahead of print].

Is Telemedicine for Headache as Effective as In-Person Visit?

In people with headache, a video consultation with a neurologist for treatment may be as effective as an in-person visit, according to a study published online ahead of print June 14 in Neurology. Researchers randomized, allocated, and consulted patients with nonacute headache via telemedicine or in a traditional manner in a noninferiority trial. Efficacy end points assessed by questionnaires at three and 12 months included change from baseline in Headache Impact Test-6 (HIT-6) and pain intensity. The primary safety end point was presence of secondary headache within 12 months after consultation. There were no differences between telemedicine and traditional consultations in HIT-6 or pain intensity over three periods. The absolute difference in HIT-6 from baseline was 0.3 at three months and 0.2 at 12 months.

Müller KI, Alstadhaug KB, Bekkelund SI. A randomized trial of telemedicine efficacy and safety for nonacute headaches. Neurology. 2017 Jun 14 [Epub ahead of print].

Minocycline Reduces Risk of Conversion From CIS to MS

The risk of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) is significantly lower with minocycline than with placebo over six months, but not over 24 months, according to a study published June 1 in the New England Journal of Medicine. This study included 142 participants who had had their first demyelinating symptoms within the previous 180 days. At 12 Canadian MS clinics, researchers randomly assigned participants to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of MS was established or until 24 months after randomization. The unadjusted risk of conversion to MS within six months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group.

Metz LM, Li DKB, Traboulsee AL, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med. 2017;376(22):2122-2133.

Can Gene Mutation Speed Memory Loss in Alzheimer’s Disease?

In a middle-aged cohort with Alzheimer’s disease risk, the BDNF Met allele is associated with steeper decline in episodic memory and executive function, according to a study published online ahead of print May 3 in Neurology. One thousand twenty-three adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention underwent BDNF genotyping and cognitive assessment at as many as five time points. A subset of participants underwent Pittsburgh compound B scanning. Compared with BDNF Val/Val homozygotes, Met carriers had steeper decline in verbal learning and memory, and in speed and flexibility. In addition, amyloid β burden moderated the relationship between BDNF and verbal learning and memory, such that Met carriers with greater amyloid β burden showed even steeper cognitive decline.

Boots EA, Schultz SA, Clark LR, et al. BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer’s Prevention. Neurology. 2017 May 3 [Epub ahead of print].

Support From Children Reduces Risk of Dementia

Positive social support from children is associated with reduced risk of dementia, whereas negative social support from children and other immediate family increases the risk, according to a study published in the Journal of Alzheimer’s Disease. Researchers analyzed 10-year follow-up data in 10,055 cognitively normal participants age 50 and older from the English Longitudinal Study of Aging. Incidence of dementia was identified from participant- or informant-reported physician diagnosed dementia or overall score of informant-completed IQCODE questionnaire. Positive social support from children significantly reduced the risk of dementia (hazard ratio, 0.83). Negative support from family and friends was significantly associated with increased risk of dementia. The causal mechanisms that create these associations require further research, said the researchers.

Khondoker M, Rafnsson SB, Morris S, et al. Positive and negative experiences of social support and risk of dementia in later life: an investigation using the English Longitudinal Study of Ageing. J Alzheimers Dis. 2017;58(1):99-108.

—Kimberly Williams

Device Helps Patients Move Paralyzed Hands After Stroke

Patients with stroke who learn to use their minds to open and close a device fitted over their paralyzed hands gain some control over their hands, according to a study published online ahead of print May 26 in Stroke. Ten survivors of chronic hemiparetic stroke with moderate-to-severe upper-limb motor impairment used a powered exoskeleton that opened and closed the affected hand using spectral power from EEG signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. At 12 weeks, participants had a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in brain–computer interface control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved.

Bundy DT, Souders L, Baranyai K, et al. Contralesional brain-computer interface control of a powered exoskeleton for motor recovery in chronic stroke survivors. Stroke. 2017 May 26 [Epub ahead of print].

Pyrimethamine Lowers Levels of ALS Biomarker

Pyrimethamine is safe and well tolerated in amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print May 8 in Annals of Neurology. Participants underwent a multicenter, open-label, nine-month dose-ranging study to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in patients with SOD1 mutations linked to familial ALS. The study included 32 patients with various SOD1 genetic mutations linked to ALS. Participants had three lumbar punctures, blood studies, and a clinical assessment of strength, motor function, quality of life, and potential adverse effects. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit six, with a mean reduction of 13.5%, and at visit nine, with a mean reduction of 10.5%.

Lange DJ, Shahbazi M, Silani V, et al. Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations. Ann Neurol. 2017 May 8 [Epub ahead of print].

Statin Use Linked to Higher Risk of Parkinson’s Disease

Statins, especially lipophilic statins, are associated with higher risk of Parkinson’s disease, according to a study published in the June issue of Movement Disorders. The association is stronger with initial use, which suggests a facilitating effect, said the investigators. Researchers performed a retrospective case–control analysis and identified 2,322 people with incident Parkinson’s disease who had been enrolled in a claims database for at least 2.5 years before diagnosis or prescription of antiparkinson medication. They matched the cases with 2,322 controls by age, gender, and a follow-up window. Statin use was significantly associated with Parkinson’s disease risk. The strongest associations were for lipophilic statins (odds ratio [OR], 1.58) versus hydrophilic statins (OR, 1.19), statins plus nonstatins (OR, 1.95), and for the initial period after starting statins.

Liu G, Sterling NW, Kong L, et al. Statins may facilitate Parkinson’s disease: insight gained from a large, national claims database. Mov Disord. 2017;32(6):913-917.

Is Moderate Drinking Associated With Cognitive Decline?

Moderate alcohol consumption is associated with adverse brain outcomes, including hippocampal atrophy, according to a study published online ahead of print June 6 in BMJ. The study included 550 men and women with a mean age of 43 at study baseline. No patient had alcohol dependence, and all underwent brain MRI at follow-up. Higher alcohol consumption over the 30-year follow-up was associated with increased odds of hippocampal atrophy in a dose-dependent fashion. People consuming more than 30 units/week of alcohol were at the highest risk, compared with abstainers. People who drank moderately had three times the odds of right-sided hippocampal atrophy. There was no protective effect of light drinking over abstinence. Higher alcohol use also was associated with differences in corpus callosum microstructure and faster decline in lexical fluency.

Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017 Jun 6 [Epub ahead of print].

Consuming Low-Fat Dairy May Increase Risk for Parkinson’s Disease

Frequently consuming low-fat dairy products may be associated with an increased risk of Parkinson’s disease, according to a study published online ahead of print June 8 in Neurology. This study is based on data from 80,736 participants in the Nurses’ Health Study and 48,610 participants in the Health Professionals Follow-Up Study, with 26 and 24 years of follow-up, respectively. Both US-based studies were conducted through mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Total dairy intake was not significantly associated with Parkinson’s disease risk, but intake of low-fat dairy foods was associated with Parkinson’s disease risk. This association appeared to result from an increased risk of Parkinson’s disease associated with skim and low-fat milk.

Hughes KC, Gao X, Kim IY, et al. Intake of dairy foods and risk of Parkinson disease. Neurology. 2017 Jun 8 [Epub ahead of print].

Elevated Brain Amyloid Increases Likelihood of Cognitive Decline

Elevated baseline brain amyloid level, compared with normal brain amyloid level, is associated with higher likelihood of cognitive decline, according to a study published June 13 in JAMA. Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal people. Participants were classified at baseline as having normal or elevated brain amyloid using PET amyloid imaging or a CSF assay of amyloid β. Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC), Mini-Mental State Examination (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-SOB), and Logical Memory Delayed Recall. Compared with the group with normal amyloid, people with elevated amyloid had worse mean scores at four years on the PACC, MMSE, and CDR-SOB. For Logical Memory Delayed Recall, between-group scores were not significantly different at four years.

Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317(22):2305-2316.

Seven Risk Genes for Insomnia Found

Researchers have found seven risk genes for insomnia, according to a study published online ahead of print June 12 in Nature Genetics. To identify genetic factors for insomnia complaints, investigators performed a genome-wide association study and a genome-wide gene-based association study in 113,006 participants. The authors identified three loci and seven genes, including MEIS1, associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample. Sex-specific analyses suggest that the sexes have different genetic architectures, in addition to shared genetic factors. The researchers also found a substantial positive genetic correlation between insomnia complaints and internalizing personality traits and metabolic traits. There was a negative correlation with subjective well-being and educational attainment.

Hammerschlag AR, Stringer S, de Leeuw CA, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet. 2017 Jun 12 [Epub ahead of print].

Is Telemedicine for Headache as Effective as In-Person Visit?

In people with headache, a video consultation with a neurologist for treatment may be as effective as an in-person visit, according to a study published online ahead of print June 14 in Neurology. Researchers randomized, allocated, and consulted patients with nonacute headache via telemedicine or in a traditional manner in a noninferiority trial. Efficacy end points assessed by questionnaires at three and 12 months included change from baseline in Headache Impact Test-6 (HIT-6) and pain intensity. The primary safety end point was presence of secondary headache within 12 months after consultation. There were no differences between telemedicine and traditional consultations in HIT-6 or pain intensity over three periods. The absolute difference in HIT-6 from baseline was 0.3 at three months and 0.2 at 12 months.

Müller KI, Alstadhaug KB, Bekkelund SI. A randomized trial of telemedicine efficacy and safety for nonacute headaches. Neurology. 2017 Jun 14 [Epub ahead of print].

Minocycline Reduces Risk of Conversion From CIS to MS

The risk of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) is significantly lower with minocycline than with placebo over six months, but not over 24 months, according to a study published June 1 in the New England Journal of Medicine. This study included 142 participants who had had their first demyelinating symptoms within the previous 180 days. At 12 Canadian MS clinics, researchers randomly assigned participants to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of MS was established or until 24 months after randomization. The unadjusted risk of conversion to MS within six months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group.

Metz LM, Li DKB, Traboulsee AL, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med. 2017;376(22):2122-2133.

Can Gene Mutation Speed Memory Loss in Alzheimer’s Disease?

In a middle-aged cohort with Alzheimer’s disease risk, the BDNF Met allele is associated with steeper decline in episodic memory and executive function, according to a study published online ahead of print May 3 in Neurology. One thousand twenty-three adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention underwent BDNF genotyping and cognitive assessment at as many as five time points. A subset of participants underwent Pittsburgh compound B scanning. Compared with BDNF Val/Val homozygotes, Met carriers had steeper decline in verbal learning and memory, and in speed and flexibility. In addition, amyloid β burden moderated the relationship between BDNF and verbal learning and memory, such that Met carriers with greater amyloid β burden showed even steeper cognitive decline.

Boots EA, Schultz SA, Clark LR, et al. BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer’s Prevention. Neurology. 2017 May 3 [Epub ahead of print].

Support From Children Reduces Risk of Dementia

Positive social support from children is associated with reduced risk of dementia, whereas negative social support from children and other immediate family increases the risk, according to a study published in the Journal of Alzheimer’s Disease. Researchers analyzed 10-year follow-up data in 10,055 cognitively normal participants age 50 and older from the English Longitudinal Study of Aging. Incidence of dementia was identified from participant- or informant-reported physician diagnosed dementia or overall score of informant-completed IQCODE questionnaire. Positive social support from children significantly reduced the risk of dementia (hazard ratio, 0.83). Negative support from family and friends was significantly associated with increased risk of dementia. The causal mechanisms that create these associations require further research, said the researchers.

Khondoker M, Rafnsson SB, Morris S, et al. Positive and negative experiences of social support and risk of dementia in later life: an investigation using the English Longitudinal Study of Ageing. J Alzheimers Dis. 2017;58(1):99-108.

—Kimberly Williams