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Noninvasive EEG may speed diagnosis of West syndrome
BANGKOK – , Hiroki Nariai, MD, reported at the International Epilepsy Congress.
Among the most promising of these potential EEG biomarkers for development of epilepsy are ictal or interictal high-frequency oscillations (HFOs) at 80 Hz or more, along with cross-frequency coupling of HFOs and delta wave activity, according to Dr. Nariai, a pediatric neurologist at the University of California, Los Angeles.
West syndrome, the most common epileptic encephalopathy during the first 2 years of life, has diverse etiologies. For example, in 250 infants with West syndrome enrolled in the United Kingdom National Infantile Spasms Consortium, a cause was identified in 64%. The etiology was genetic in 14% of subjects, a structural-congenital anomaly in 11%, tuberous sclerosis – a genetic-structural abnormality – in 10%, stroke in 22%, a metabolic defect in 5%, and infection in 2% (Epilepsia. 2015 Apr;56[4]:617-25).
West syndrome is rare, with an estimated prevalence of roughly 1 per 6,000 live births, but the associated mortality is high: 31% on average. And West syndrome often brings severe neurodevelopmental morbidity, with normal or near-normal intelligence present in only 25% of survivors.
An intensive search is on for an objective, reliable diagnostic biomarker – be it electroencephalographic, biochemical, or perhaps a neuroimaging finding – because the clinical diagnosis of West syndrome is highly subjective. It relies upon the triad of epileptic spasms, developmental regression or psychomotor delay, and hypsarrhythmia, which is a chaotic, disorganized, patternless form of brain electrical activity. And while that description makes hypsarrhythmia sound as if it should be easily recognizable, in fact that’s often not the case: Interrater reliability was poor in a study of six pediatric EEG experts at four centers who viewed 5-minute-long EEG samples obtained from 22 patients with infantile spasms (Epilepsia. 2015 Jan;56[1]:77-81), Dr. Nariai noted at the congress, sponsored by the International League Against Epilepsy.
“The clinical trial is maybe not so useful,” he observed.
The hunt for a reliable biomarker is further fueled by evidence that early diagnosis and treatment of West syndrome and other etiologies of infantile spasms makes a real difference. Indeed, investigators found in the United Kingdom Infantile Spasms Study that increasing lag time from onset of spasms to initiation of treatment was associated in stepwise fashion with significantly lower IQ at 4 years of age. While infants who started treatment within 7 days of onset of the seizure disorder had a mean IQ of 76.2 at age 4 years, those with an 8- to 14-day lag time between symptom onset and treatment averaged an additional 3.9-point decrement in IQ. A 15- to 30-day delay was associated with a 7.8-point reduction in IQ, compared with the reference group, while the decrease in IQ averaged 11.7 points in infants with a 1- to 2-month lag time and 15.6 points in those with a lag time of more than 2 months (Epilepsia. 2011 Jul;52[7]:1359-64).
At the start of the decade, Dr. Nariai and other investigators demonstrated that pathologic HFOs recorded during invasive EEG monitoring in conjunction with epilepsy surgery served as a reliable biomarker of epilepsy. While this was an important observation, a biomarker obtained through invasive monitoring during brain surgery clearly has very limited clinical applicability. But more recently, Dr. Nariai and his coinvestigators in the Tuberous Sclerosis Complex Autism Center of Excellence Network reported that noninvasive detection of interictal HFO fast ripples in the 250-500 Hz range via scalp EEG showed promise as a biomarker of epilepsy. Sensitivity of this far more practical approach to the detection of fast ripples was excellent, whether analyzed visually or by automatic detector (Clin Neurophysiol. 2018 Jul;129[7]:1458-66).
Moreover, in a recent, not-yet published study that Dr. Nariai and coworkers conducted in 24 infants with active epileptic spasms and 6 controls, noninvasive objective measurement of HFO rate using scalp EEG had an 83% sensitivity and 100% specificity for active epileptic spasms, while the modulation index of HFO and delta coupling in the 3-4 Hz range showed 74% sensitivity and 86% specificity.
If future studies validate the utility of detection of HFOs above a defined threshold or another noninvasively obtained EEG biomarker for diagnosis of epilepsy, the same strategy would presumably also be applicable for monitoring response to antiepileptic therapies, thereby eliminating the traditional trial-and-error approach to treatment. This would be a particularly important application in patients with West syndrome, where it’s believed that the electrical activity itself is contributing to the progressive – and often rapid – loss of cognitive function and behavioral disturbances. Thus, unlike in most other forms of epilepsy, the treatment goal isn’t merely to suppress the seizures, but also to achieve disease modification by eliminating the underlying subclinical EEG abnormalities, he explained.
A reliable biomarker would also be a boon in selecting the best participants for clinical trials of new antiseizure therapies.
Dr. Nariai reported having no financial conflicts regarding his presentation. His work is funded by research foundations and the National Institutes of Health.
BANGKOK – , Hiroki Nariai, MD, reported at the International Epilepsy Congress.
Among the most promising of these potential EEG biomarkers for development of epilepsy are ictal or interictal high-frequency oscillations (HFOs) at 80 Hz or more, along with cross-frequency coupling of HFOs and delta wave activity, according to Dr. Nariai, a pediatric neurologist at the University of California, Los Angeles.
West syndrome, the most common epileptic encephalopathy during the first 2 years of life, has diverse etiologies. For example, in 250 infants with West syndrome enrolled in the United Kingdom National Infantile Spasms Consortium, a cause was identified in 64%. The etiology was genetic in 14% of subjects, a structural-congenital anomaly in 11%, tuberous sclerosis – a genetic-structural abnormality – in 10%, stroke in 22%, a metabolic defect in 5%, and infection in 2% (Epilepsia. 2015 Apr;56[4]:617-25).
West syndrome is rare, with an estimated prevalence of roughly 1 per 6,000 live births, but the associated mortality is high: 31% on average. And West syndrome often brings severe neurodevelopmental morbidity, with normal or near-normal intelligence present in only 25% of survivors.
An intensive search is on for an objective, reliable diagnostic biomarker – be it electroencephalographic, biochemical, or perhaps a neuroimaging finding – because the clinical diagnosis of West syndrome is highly subjective. It relies upon the triad of epileptic spasms, developmental regression or psychomotor delay, and hypsarrhythmia, which is a chaotic, disorganized, patternless form of brain electrical activity. And while that description makes hypsarrhythmia sound as if it should be easily recognizable, in fact that’s often not the case: Interrater reliability was poor in a study of six pediatric EEG experts at four centers who viewed 5-minute-long EEG samples obtained from 22 patients with infantile spasms (Epilepsia. 2015 Jan;56[1]:77-81), Dr. Nariai noted at the congress, sponsored by the International League Against Epilepsy.
“The clinical trial is maybe not so useful,” he observed.
The hunt for a reliable biomarker is further fueled by evidence that early diagnosis and treatment of West syndrome and other etiologies of infantile spasms makes a real difference. Indeed, investigators found in the United Kingdom Infantile Spasms Study that increasing lag time from onset of spasms to initiation of treatment was associated in stepwise fashion with significantly lower IQ at 4 years of age. While infants who started treatment within 7 days of onset of the seizure disorder had a mean IQ of 76.2 at age 4 years, those with an 8- to 14-day lag time between symptom onset and treatment averaged an additional 3.9-point decrement in IQ. A 15- to 30-day delay was associated with a 7.8-point reduction in IQ, compared with the reference group, while the decrease in IQ averaged 11.7 points in infants with a 1- to 2-month lag time and 15.6 points in those with a lag time of more than 2 months (Epilepsia. 2011 Jul;52[7]:1359-64).
At the start of the decade, Dr. Nariai and other investigators demonstrated that pathologic HFOs recorded during invasive EEG monitoring in conjunction with epilepsy surgery served as a reliable biomarker of epilepsy. While this was an important observation, a biomarker obtained through invasive monitoring during brain surgery clearly has very limited clinical applicability. But more recently, Dr. Nariai and his coinvestigators in the Tuberous Sclerosis Complex Autism Center of Excellence Network reported that noninvasive detection of interictal HFO fast ripples in the 250-500 Hz range via scalp EEG showed promise as a biomarker of epilepsy. Sensitivity of this far more practical approach to the detection of fast ripples was excellent, whether analyzed visually or by automatic detector (Clin Neurophysiol. 2018 Jul;129[7]:1458-66).
Moreover, in a recent, not-yet published study that Dr. Nariai and coworkers conducted in 24 infants with active epileptic spasms and 6 controls, noninvasive objective measurement of HFO rate using scalp EEG had an 83% sensitivity and 100% specificity for active epileptic spasms, while the modulation index of HFO and delta coupling in the 3-4 Hz range showed 74% sensitivity and 86% specificity.
If future studies validate the utility of detection of HFOs above a defined threshold or another noninvasively obtained EEG biomarker for diagnosis of epilepsy, the same strategy would presumably also be applicable for monitoring response to antiepileptic therapies, thereby eliminating the traditional trial-and-error approach to treatment. This would be a particularly important application in patients with West syndrome, where it’s believed that the electrical activity itself is contributing to the progressive – and often rapid – loss of cognitive function and behavioral disturbances. Thus, unlike in most other forms of epilepsy, the treatment goal isn’t merely to suppress the seizures, but also to achieve disease modification by eliminating the underlying subclinical EEG abnormalities, he explained.
A reliable biomarker would also be a boon in selecting the best participants for clinical trials of new antiseizure therapies.
Dr. Nariai reported having no financial conflicts regarding his presentation. His work is funded by research foundations and the National Institutes of Health.
BANGKOK – , Hiroki Nariai, MD, reported at the International Epilepsy Congress.
Among the most promising of these potential EEG biomarkers for development of epilepsy are ictal or interictal high-frequency oscillations (HFOs) at 80 Hz or more, along with cross-frequency coupling of HFOs and delta wave activity, according to Dr. Nariai, a pediatric neurologist at the University of California, Los Angeles.
West syndrome, the most common epileptic encephalopathy during the first 2 years of life, has diverse etiologies. For example, in 250 infants with West syndrome enrolled in the United Kingdom National Infantile Spasms Consortium, a cause was identified in 64%. The etiology was genetic in 14% of subjects, a structural-congenital anomaly in 11%, tuberous sclerosis – a genetic-structural abnormality – in 10%, stroke in 22%, a metabolic defect in 5%, and infection in 2% (Epilepsia. 2015 Apr;56[4]:617-25).
West syndrome is rare, with an estimated prevalence of roughly 1 per 6,000 live births, but the associated mortality is high: 31% on average. And West syndrome often brings severe neurodevelopmental morbidity, with normal or near-normal intelligence present in only 25% of survivors.
An intensive search is on for an objective, reliable diagnostic biomarker – be it electroencephalographic, biochemical, or perhaps a neuroimaging finding – because the clinical diagnosis of West syndrome is highly subjective. It relies upon the triad of epileptic spasms, developmental regression or psychomotor delay, and hypsarrhythmia, which is a chaotic, disorganized, patternless form of brain electrical activity. And while that description makes hypsarrhythmia sound as if it should be easily recognizable, in fact that’s often not the case: Interrater reliability was poor in a study of six pediatric EEG experts at four centers who viewed 5-minute-long EEG samples obtained from 22 patients with infantile spasms (Epilepsia. 2015 Jan;56[1]:77-81), Dr. Nariai noted at the congress, sponsored by the International League Against Epilepsy.
“The clinical trial is maybe not so useful,” he observed.
The hunt for a reliable biomarker is further fueled by evidence that early diagnosis and treatment of West syndrome and other etiologies of infantile spasms makes a real difference. Indeed, investigators found in the United Kingdom Infantile Spasms Study that increasing lag time from onset of spasms to initiation of treatment was associated in stepwise fashion with significantly lower IQ at 4 years of age. While infants who started treatment within 7 days of onset of the seizure disorder had a mean IQ of 76.2 at age 4 years, those with an 8- to 14-day lag time between symptom onset and treatment averaged an additional 3.9-point decrement in IQ. A 15- to 30-day delay was associated with a 7.8-point reduction in IQ, compared with the reference group, while the decrease in IQ averaged 11.7 points in infants with a 1- to 2-month lag time and 15.6 points in those with a lag time of more than 2 months (Epilepsia. 2011 Jul;52[7]:1359-64).
At the start of the decade, Dr. Nariai and other investigators demonstrated that pathologic HFOs recorded during invasive EEG monitoring in conjunction with epilepsy surgery served as a reliable biomarker of epilepsy. While this was an important observation, a biomarker obtained through invasive monitoring during brain surgery clearly has very limited clinical applicability. But more recently, Dr. Nariai and his coinvestigators in the Tuberous Sclerosis Complex Autism Center of Excellence Network reported that noninvasive detection of interictal HFO fast ripples in the 250-500 Hz range via scalp EEG showed promise as a biomarker of epilepsy. Sensitivity of this far more practical approach to the detection of fast ripples was excellent, whether analyzed visually or by automatic detector (Clin Neurophysiol. 2018 Jul;129[7]:1458-66).
Moreover, in a recent, not-yet published study that Dr. Nariai and coworkers conducted in 24 infants with active epileptic spasms and 6 controls, noninvasive objective measurement of HFO rate using scalp EEG had an 83% sensitivity and 100% specificity for active epileptic spasms, while the modulation index of HFO and delta coupling in the 3-4 Hz range showed 74% sensitivity and 86% specificity.
If future studies validate the utility of detection of HFOs above a defined threshold or another noninvasively obtained EEG biomarker for diagnosis of epilepsy, the same strategy would presumably also be applicable for monitoring response to antiepileptic therapies, thereby eliminating the traditional trial-and-error approach to treatment. This would be a particularly important application in patients with West syndrome, where it’s believed that the electrical activity itself is contributing to the progressive – and often rapid – loss of cognitive function and behavioral disturbances. Thus, unlike in most other forms of epilepsy, the treatment goal isn’t merely to suppress the seizures, but also to achieve disease modification by eliminating the underlying subclinical EEG abnormalities, he explained.
A reliable biomarker would also be a boon in selecting the best participants for clinical trials of new antiseizure therapies.
Dr. Nariai reported having no financial conflicts regarding his presentation. His work is funded by research foundations and the National Institutes of Health.
REPORTING FROM IEC 2019
Cutaneous reaction to AEDs? Think autoimmune epilepsy
BANGKOK – Cutaneous reactions to antiepileptic drugs in patients with chronic epilepsy suggest increased likelihood of an autoimmune element to their seizure disorder, Fernando Cendes, MD, PhD, reported at the International Epilepsy Congress.
“My recommendation based on our findings is that if you have a patient who has a history of skin reactions to AEDs [antiepileptic drugs], or who has psychosis, or who has a very strange response to antiepileptic medication – meaning that at some points they are refractory and at other points they are very well controlled – I think those patients are probably at risk for having an autoantibody,” he said at the congress sponsored by the International League Against Epilepsy.
Screening for autoantibodies in such patients is appropriate. However, there’s a caveat: “The thing is, we don’t have evidence that treating these autoantibodies with immunotherapy will have any benefit on seizure control in these patients. We don’t have that data yet, but we are looking into it,” according to Dr. Cendes, professor of neurology at the State University of Campinas (Brazil).
He presented a study of 221 consecutive adults with severe chronic refractory epilepsy as evidenced by a mean disease duration of nearly 29 years, with an average of 5.93 seizures per month. A total of 77% had a structural etiology for their epilepsy, in most cases hippocampal sclerosis. In 19% of patients, the etiology was unknown. Overall, 95% of subjects had focal epilepsy, and the remainder had generalized epilepsy. All underwent serum testing for a variety of antibodies against neuronal surface antigens that have been implicated in encephalitis, seizures, and/or psychosis. Those who tested positive then underwent confirmatory testing of their cerebrospinal fluid.
The impetus for this study, the neurologist explained, is that although it’s now well established that seizures are a common clinical expression of acute- and subacute-phase autoimmune encephalitis marked by neuronal autoantibodies, little is known about the relationship between chronic epilepsy and such antibodies.
Only five Brazilian patients with chronic epilepsy, or 2.2%, tested positive for autoantibodies, all of whom had mesial temporal lobe epilepsy with hippocampal sclerosis. This suggests a possible autoimmune etiology for hippocampal sclerosis. Three of the five patients had anti-N-methyl-D-aspartate receptor antibodies (anti-NMDA) and two had antiglutamic acid decarboxylate antibodies (anti-GAD). No one was positive for anti–leucine-rich glioma-inactivated 1 antibodies (anti-LGI1), anti–contactin-associated proteinlike 2 (anti-caspr2), anti-glutamate receptor antibodies (anti-AMPAr), or anti–gamma-aminobutyric acid receptor antibodies (anti-GABAr).
The autoantibody-negative and the much smaller autoantibody-positive groups didn’t differ significantly in terms of demographics, seizure frequency, disease duration, drug resistance, cognitive impairment, comorbid autoimmune conditions, or history of status epilepticus. Indeed, only two between-group differences were found: fluctuation in seizure control was an issue in 10.6% of autoantibody-negative and 40% of autoantibody-positive patients, and cutaneous adverse reactions to antiepileptic drugs were noted in 10.6% of antibody-negative and 60% of antibody-positive patients. Psychiatric comorbidities were present in 49.5% of autoantibody-negative patients as compared with 80% – that is, four of five – who were autoantibody-positive, a trend that didn’t achieve statistical significance.
Asked if he thinks the autoantibodies found in a small subset of patients with chronic epilepsy were a cause or an effect of repeated seizures for so long, Dr. Cendes replied, “That’s a very interesting question, and I don’t have an answer, actually. But if seizures trigger development of these antibodies – and remember, this population we’re talking about had many, many seizures over the years – I would expect antibodies to be more frequent than the figure we found.”
He reported having no financial conflicts regarding his study.
SOURCE: Watanabe N et al. IEC 2019, Abstract P004.
BANGKOK – Cutaneous reactions to antiepileptic drugs in patients with chronic epilepsy suggest increased likelihood of an autoimmune element to their seizure disorder, Fernando Cendes, MD, PhD, reported at the International Epilepsy Congress.
“My recommendation based on our findings is that if you have a patient who has a history of skin reactions to AEDs [antiepileptic drugs], or who has psychosis, or who has a very strange response to antiepileptic medication – meaning that at some points they are refractory and at other points they are very well controlled – I think those patients are probably at risk for having an autoantibody,” he said at the congress sponsored by the International League Against Epilepsy.
Screening for autoantibodies in such patients is appropriate. However, there’s a caveat: “The thing is, we don’t have evidence that treating these autoantibodies with immunotherapy will have any benefit on seizure control in these patients. We don’t have that data yet, but we are looking into it,” according to Dr. Cendes, professor of neurology at the State University of Campinas (Brazil).
He presented a study of 221 consecutive adults with severe chronic refractory epilepsy as evidenced by a mean disease duration of nearly 29 years, with an average of 5.93 seizures per month. A total of 77% had a structural etiology for their epilepsy, in most cases hippocampal sclerosis. In 19% of patients, the etiology was unknown. Overall, 95% of subjects had focal epilepsy, and the remainder had generalized epilepsy. All underwent serum testing for a variety of antibodies against neuronal surface antigens that have been implicated in encephalitis, seizures, and/or psychosis. Those who tested positive then underwent confirmatory testing of their cerebrospinal fluid.
The impetus for this study, the neurologist explained, is that although it’s now well established that seizures are a common clinical expression of acute- and subacute-phase autoimmune encephalitis marked by neuronal autoantibodies, little is known about the relationship between chronic epilepsy and such antibodies.
Only five Brazilian patients with chronic epilepsy, or 2.2%, tested positive for autoantibodies, all of whom had mesial temporal lobe epilepsy with hippocampal sclerosis. This suggests a possible autoimmune etiology for hippocampal sclerosis. Three of the five patients had anti-N-methyl-D-aspartate receptor antibodies (anti-NMDA) and two had antiglutamic acid decarboxylate antibodies (anti-GAD). No one was positive for anti–leucine-rich glioma-inactivated 1 antibodies (anti-LGI1), anti–contactin-associated proteinlike 2 (anti-caspr2), anti-glutamate receptor antibodies (anti-AMPAr), or anti–gamma-aminobutyric acid receptor antibodies (anti-GABAr).
The autoantibody-negative and the much smaller autoantibody-positive groups didn’t differ significantly in terms of demographics, seizure frequency, disease duration, drug resistance, cognitive impairment, comorbid autoimmune conditions, or history of status epilepticus. Indeed, only two between-group differences were found: fluctuation in seizure control was an issue in 10.6% of autoantibody-negative and 40% of autoantibody-positive patients, and cutaneous adverse reactions to antiepileptic drugs were noted in 10.6% of antibody-negative and 60% of antibody-positive patients. Psychiatric comorbidities were present in 49.5% of autoantibody-negative patients as compared with 80% – that is, four of five – who were autoantibody-positive, a trend that didn’t achieve statistical significance.
Asked if he thinks the autoantibodies found in a small subset of patients with chronic epilepsy were a cause or an effect of repeated seizures for so long, Dr. Cendes replied, “That’s a very interesting question, and I don’t have an answer, actually. But if seizures trigger development of these antibodies – and remember, this population we’re talking about had many, many seizures over the years – I would expect antibodies to be more frequent than the figure we found.”
He reported having no financial conflicts regarding his study.
SOURCE: Watanabe N et al. IEC 2019, Abstract P004.
BANGKOK – Cutaneous reactions to antiepileptic drugs in patients with chronic epilepsy suggest increased likelihood of an autoimmune element to their seizure disorder, Fernando Cendes, MD, PhD, reported at the International Epilepsy Congress.
“My recommendation based on our findings is that if you have a patient who has a history of skin reactions to AEDs [antiepileptic drugs], or who has psychosis, or who has a very strange response to antiepileptic medication – meaning that at some points they are refractory and at other points they are very well controlled – I think those patients are probably at risk for having an autoantibody,” he said at the congress sponsored by the International League Against Epilepsy.
Screening for autoantibodies in such patients is appropriate. However, there’s a caveat: “The thing is, we don’t have evidence that treating these autoantibodies with immunotherapy will have any benefit on seizure control in these patients. We don’t have that data yet, but we are looking into it,” according to Dr. Cendes, professor of neurology at the State University of Campinas (Brazil).
He presented a study of 221 consecutive adults with severe chronic refractory epilepsy as evidenced by a mean disease duration of nearly 29 years, with an average of 5.93 seizures per month. A total of 77% had a structural etiology for their epilepsy, in most cases hippocampal sclerosis. In 19% of patients, the etiology was unknown. Overall, 95% of subjects had focal epilepsy, and the remainder had generalized epilepsy. All underwent serum testing for a variety of antibodies against neuronal surface antigens that have been implicated in encephalitis, seizures, and/or psychosis. Those who tested positive then underwent confirmatory testing of their cerebrospinal fluid.
The impetus for this study, the neurologist explained, is that although it’s now well established that seizures are a common clinical expression of acute- and subacute-phase autoimmune encephalitis marked by neuronal autoantibodies, little is known about the relationship between chronic epilepsy and such antibodies.
Only five Brazilian patients with chronic epilepsy, or 2.2%, tested positive for autoantibodies, all of whom had mesial temporal lobe epilepsy with hippocampal sclerosis. This suggests a possible autoimmune etiology for hippocampal sclerosis. Three of the five patients had anti-N-methyl-D-aspartate receptor antibodies (anti-NMDA) and two had antiglutamic acid decarboxylate antibodies (anti-GAD). No one was positive for anti–leucine-rich glioma-inactivated 1 antibodies (anti-LGI1), anti–contactin-associated proteinlike 2 (anti-caspr2), anti-glutamate receptor antibodies (anti-AMPAr), or anti–gamma-aminobutyric acid receptor antibodies (anti-GABAr).
The autoantibody-negative and the much smaller autoantibody-positive groups didn’t differ significantly in terms of demographics, seizure frequency, disease duration, drug resistance, cognitive impairment, comorbid autoimmune conditions, or history of status epilepticus. Indeed, only two between-group differences were found: fluctuation in seizure control was an issue in 10.6% of autoantibody-negative and 40% of autoantibody-positive patients, and cutaneous adverse reactions to antiepileptic drugs were noted in 10.6% of antibody-negative and 60% of antibody-positive patients. Psychiatric comorbidities were present in 49.5% of autoantibody-negative patients as compared with 80% – that is, four of five – who were autoantibody-positive, a trend that didn’t achieve statistical significance.
Asked if he thinks the autoantibodies found in a small subset of patients with chronic epilepsy were a cause or an effect of repeated seizures for so long, Dr. Cendes replied, “That’s a very interesting question, and I don’t have an answer, actually. But if seizures trigger development of these antibodies – and remember, this population we’re talking about had many, many seizures over the years – I would expect antibodies to be more frequent than the figure we found.”
He reported having no financial conflicts regarding his study.
SOURCE: Watanabe N et al. IEC 2019, Abstract P004.
REPORTING FROM IEC 2019
Discovery of peer review and patient safety reports
Question: A patient died unexpectedly during hospitalization for a diabetic foot infection. The autopsy revealed the presence of a large saddle pulmonary embolus. The hospital’s peer review committee met to determine if care was suboptimal and whether prophylactic anticoagulation should have been used. When the attending doctor was subsequently sued for malpractice, the plaintiff’s attorney sought to subpoena all of the medical records, including the minutes of the peer review committee. Given this hypothetical scenario, which of the following can occur?
A. “Discovery” is the legal term given to the process during the pretrial phase for amassing relevant documents and other information.
B. A subpoena duces tecum, which is a court order for the production of relevant documents and one that should normally be obeyed, may be issued.
C. The hospital declines to hand over certain types of hospital records, such as peer review minutes, which in this case are statutorily protected from discovery.
D. The plaintiff attorney goes to the judge for an order to compel production and may or may not be successful.
E. All are correct.
Answer: E. Physicians and other participants regularly meet, under strict confidential conditions, to discuss adverse events that occur in their institution. Such records are protected from “discovery,” which is a pretrial procedure for collecting evidence in preparation for trial. The rationale for keeping these records beyond the reach of the discovery process is to encourage participants to engage in candid and free-rein analysis of adverse medical events so as to avoid future mishaps. If the content and nature of these discussions were freely available to parties in litigation, there would be a natural reluctance to express one’s viewpoints in a forthright manner.
Any given state’s statute on discovery requires careful reading because it could differ from another state’s directive – with important legal consequences. As an example, Hawaii’s statute1 contains several inclusions and exclusions and reads in part: “... the information and data protected shall include proceedings and records of a peer review committee, hospital quality assurance committee, or health care review organization that include recordings, transcripts, minutes, and summaries of meetings, conversations, notes, materials, or reports created for, by, or at the direction of a peer review committee, quality assurance committee, or a health care review organization when related to a medical error reporting system. ... Information and data protected from discovery shall not include incident reports, occurrence reports, statements, or similar reports that state facts concerning a specific situation and shall not include records made in the regular course of business by a hospital ... including patient medical records. Original sources of information ... shall not be construed as being immune from discovery ... merely because they were reviewed ... or were in fact submitted to, a health care review organization.”
Predictably, plaintiff attorneys in a medical malpractice lawsuit will attempt to discover information regarding adverse events, hoping to learn about potential errors and judgment lapses, and thus gain an advantage over the defendant doctor and/or hospital. Several recent court cases highlight the contentious nature regarding whether a particular hospital report is to be deemed discoverable. Organized medicine, led by the American Medical Association, has mounted a vigorous response in arguing against the release of peer review and patient safety documents.
The AMA2 recently weighed in on the case of Daley v. Teruel and Ingalls Memorial Hospital. In 2013, a renal failure patient died in an Illinois hospital from injuries that arose from prolonged hypoglycemia. She had received insulin, but when her blood glucose dropped to 16 mg/dl, the treatment team was not alerted and she was later found unresponsive with irreversible brain damage. The issue was whether incident reports from the case that were submitted to a certified PSO (patient safety organization) could be discovered. The Federal Patient Safety and Quality Improvement Act (PSQIA) had created PSOs to aggregate data from multiple sources to reduce adverse events and errors and improve medication safety.
An Illinois lower court ruled that, as part of the discovery process, the hospital had to turn over the report. However, the Illinois Appellate Court ruled in favor of the hospital, holding that the PSQIA protects the report because it is a “patient safety work product.”3 The AMA amicus brief had emphasized that Congress created a safeguarded patient safety process under the PSQIA to encourage hospitals to submit patient safety outcomes without fear of increased liability risk and that “these voluntarily created materials should be used for their intended purpose, not as a roadmap for litigation.”
New Jersey has also ruled against the discovery of a hospital’s self-critical report of a patient’s care, prepared in accordance with New Jersey’s Patient Safety Act.4 The plaintiff alleged that, when she reported to the emergency room at Chilton Medical Center complaining of persistent abdominal pain, fever, body aches, weakness, and a phlegmatic cough, she was incorrectly diagnosed as having pneumonia. In fact, she had appendicitis and a pelvic abscess. The New Jersey Supreme Court affirmed the panel’s order shielding the redacted document from discovery, but it reversed the judgment to the extent it ended the defendants’ discovery obligation with respect to this dispute, requiring instead that the lower court address, through current discovery rules, the proper balancing of interests between requesting and responding parties.
In a recent Michigan case,5 the trial court had earlier ruled that peer review documents at issue were in fact discoverable. Like similar statutes elsewhere, Michigan’s peer review privileges serve to encourage participation to improve on patient morbidity and mortality. The case centered on a court order compelling a Michigan hospital to release a physician’s credentialing file in a medical liability lawsuit on the narrow basis that the nondiscoverability privilege applied only to peer review deliberations and was inapplicable in the case. The trial judge had opined that, if all materials viewed by peer review committees were deemed undiscoverable, a hospital could never be held accountable for any negligent act within the purview of the committee. In its amicus brief in support of the hospital, the AMA argued that Michigan’s peer review privilege has historically spanned the bounds of the actual peer review process, and it countered that hospitals can be held liable – and are regularly held liable – without opening up these documents and that plaintiffs can use the same discovery mechanisms generally available to plaintiffs in other lawsuits.6 The case is currently under appeal.
In contrast, at least two state supreme courts have ruled to limit protections from discovery. The Florida Supreme Court has held that the federal law was intended to improve overall health care rather than to act as a shield to providers. In a case of alleged malpractice with severe neurological injuries, the court took a restrictive interpretation of the PSQIA as it relates to Florida’s risk-management and discovery laws, holding that patient safety work and related reports, when required by state law, do not come under the definition of patient safety work product and were therefore discoverable.7
The Pennsylvania Supreme Court has likewise ruled that documents generated by a hospital’s outside contractor are not protected from discovery under the state’s Peer Review Protection Act. It agreed with a lower-court ruling that Monongahela Valley Hospital could not claim privilege for a performance file on an emergency department physician employed by the hospital’s contractor University of Pittsburgh Medical Center Emergency Medicine.8 The case alleged that the plaintiff’s chest and back pain was misdiagnosed as reflux disease when in fact it was a myocardial infarct.
Dr. Tan is professor of medicine and former adjunct professor of law at the University of Hawaii. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at siang@hawaii.edu.
References
1. Hawaii Revised Statutes §624-25.5 (2012).
2. AMA fights to protect patient-safety work from legal discovery. AMA Morning Rounds. 2018 Aug 1.
3. Daley v. Teruel and Ingalls Memorial Hospital, 2018 Ill. App. LEXIS 440 (Ill. App. Ct. 2018).
4. Brugaletta v. Garcia, 190 A.3d 419 (NJ. 2018).
5. Dwyer v. Ascension Crittenton Hospital. Michigan Supreme Court SC: 158668, 919 N.W.2d 407 (Mi. 2018).
6. Appellate court case puts peer-review protections in danger. AMA Morning Rounds. 2019 Mar 29.
7. Charles v. Southern Baptist Hospital of Florida, Inc., 2017 Fla. LEXIS 231 (Fla. Jan. 31, 2017).
8. Reginelli v. Boggs, 2018 Pa. LEXIS 1503 (Pa. 2018).
Question: A patient died unexpectedly during hospitalization for a diabetic foot infection. The autopsy revealed the presence of a large saddle pulmonary embolus. The hospital’s peer review committee met to determine if care was suboptimal and whether prophylactic anticoagulation should have been used. When the attending doctor was subsequently sued for malpractice, the plaintiff’s attorney sought to subpoena all of the medical records, including the minutes of the peer review committee. Given this hypothetical scenario, which of the following can occur?
A. “Discovery” is the legal term given to the process during the pretrial phase for amassing relevant documents and other information.
B. A subpoena duces tecum, which is a court order for the production of relevant documents and one that should normally be obeyed, may be issued.
C. The hospital declines to hand over certain types of hospital records, such as peer review minutes, which in this case are statutorily protected from discovery.
D. The plaintiff attorney goes to the judge for an order to compel production and may or may not be successful.
E. All are correct.
Answer: E. Physicians and other participants regularly meet, under strict confidential conditions, to discuss adverse events that occur in their institution. Such records are protected from “discovery,” which is a pretrial procedure for collecting evidence in preparation for trial. The rationale for keeping these records beyond the reach of the discovery process is to encourage participants to engage in candid and free-rein analysis of adverse medical events so as to avoid future mishaps. If the content and nature of these discussions were freely available to parties in litigation, there would be a natural reluctance to express one’s viewpoints in a forthright manner.
Any given state’s statute on discovery requires careful reading because it could differ from another state’s directive – with important legal consequences. As an example, Hawaii’s statute1 contains several inclusions and exclusions and reads in part: “... the information and data protected shall include proceedings and records of a peer review committee, hospital quality assurance committee, or health care review organization that include recordings, transcripts, minutes, and summaries of meetings, conversations, notes, materials, or reports created for, by, or at the direction of a peer review committee, quality assurance committee, or a health care review organization when related to a medical error reporting system. ... Information and data protected from discovery shall not include incident reports, occurrence reports, statements, or similar reports that state facts concerning a specific situation and shall not include records made in the regular course of business by a hospital ... including patient medical records. Original sources of information ... shall not be construed as being immune from discovery ... merely because they were reviewed ... or were in fact submitted to, a health care review organization.”
Predictably, plaintiff attorneys in a medical malpractice lawsuit will attempt to discover information regarding adverse events, hoping to learn about potential errors and judgment lapses, and thus gain an advantage over the defendant doctor and/or hospital. Several recent court cases highlight the contentious nature regarding whether a particular hospital report is to be deemed discoverable. Organized medicine, led by the American Medical Association, has mounted a vigorous response in arguing against the release of peer review and patient safety documents.
The AMA2 recently weighed in on the case of Daley v. Teruel and Ingalls Memorial Hospital. In 2013, a renal failure patient died in an Illinois hospital from injuries that arose from prolonged hypoglycemia. She had received insulin, but when her blood glucose dropped to 16 mg/dl, the treatment team was not alerted and she was later found unresponsive with irreversible brain damage. The issue was whether incident reports from the case that were submitted to a certified PSO (patient safety organization) could be discovered. The Federal Patient Safety and Quality Improvement Act (PSQIA) had created PSOs to aggregate data from multiple sources to reduce adverse events and errors and improve medication safety.
An Illinois lower court ruled that, as part of the discovery process, the hospital had to turn over the report. However, the Illinois Appellate Court ruled in favor of the hospital, holding that the PSQIA protects the report because it is a “patient safety work product.”3 The AMA amicus brief had emphasized that Congress created a safeguarded patient safety process under the PSQIA to encourage hospitals to submit patient safety outcomes without fear of increased liability risk and that “these voluntarily created materials should be used for their intended purpose, not as a roadmap for litigation.”
New Jersey has also ruled against the discovery of a hospital’s self-critical report of a patient’s care, prepared in accordance with New Jersey’s Patient Safety Act.4 The plaintiff alleged that, when she reported to the emergency room at Chilton Medical Center complaining of persistent abdominal pain, fever, body aches, weakness, and a phlegmatic cough, she was incorrectly diagnosed as having pneumonia. In fact, she had appendicitis and a pelvic abscess. The New Jersey Supreme Court affirmed the panel’s order shielding the redacted document from discovery, but it reversed the judgment to the extent it ended the defendants’ discovery obligation with respect to this dispute, requiring instead that the lower court address, through current discovery rules, the proper balancing of interests between requesting and responding parties.
In a recent Michigan case,5 the trial court had earlier ruled that peer review documents at issue were in fact discoverable. Like similar statutes elsewhere, Michigan’s peer review privileges serve to encourage participation to improve on patient morbidity and mortality. The case centered on a court order compelling a Michigan hospital to release a physician’s credentialing file in a medical liability lawsuit on the narrow basis that the nondiscoverability privilege applied only to peer review deliberations and was inapplicable in the case. The trial judge had opined that, if all materials viewed by peer review committees were deemed undiscoverable, a hospital could never be held accountable for any negligent act within the purview of the committee. In its amicus brief in support of the hospital, the AMA argued that Michigan’s peer review privilege has historically spanned the bounds of the actual peer review process, and it countered that hospitals can be held liable – and are regularly held liable – without opening up these documents and that plaintiffs can use the same discovery mechanisms generally available to plaintiffs in other lawsuits.6 The case is currently under appeal.
In contrast, at least two state supreme courts have ruled to limit protections from discovery. The Florida Supreme Court has held that the federal law was intended to improve overall health care rather than to act as a shield to providers. In a case of alleged malpractice with severe neurological injuries, the court took a restrictive interpretation of the PSQIA as it relates to Florida’s risk-management and discovery laws, holding that patient safety work and related reports, when required by state law, do not come under the definition of patient safety work product and were therefore discoverable.7
The Pennsylvania Supreme Court has likewise ruled that documents generated by a hospital’s outside contractor are not protected from discovery under the state’s Peer Review Protection Act. It agreed with a lower-court ruling that Monongahela Valley Hospital could not claim privilege for a performance file on an emergency department physician employed by the hospital’s contractor University of Pittsburgh Medical Center Emergency Medicine.8 The case alleged that the plaintiff’s chest and back pain was misdiagnosed as reflux disease when in fact it was a myocardial infarct.
Dr. Tan is professor of medicine and former adjunct professor of law at the University of Hawaii. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at siang@hawaii.edu.
References
1. Hawaii Revised Statutes §624-25.5 (2012).
2. AMA fights to protect patient-safety work from legal discovery. AMA Morning Rounds. 2018 Aug 1.
3. Daley v. Teruel and Ingalls Memorial Hospital, 2018 Ill. App. LEXIS 440 (Ill. App. Ct. 2018).
4. Brugaletta v. Garcia, 190 A.3d 419 (NJ. 2018).
5. Dwyer v. Ascension Crittenton Hospital. Michigan Supreme Court SC: 158668, 919 N.W.2d 407 (Mi. 2018).
6. Appellate court case puts peer-review protections in danger. AMA Morning Rounds. 2019 Mar 29.
7. Charles v. Southern Baptist Hospital of Florida, Inc., 2017 Fla. LEXIS 231 (Fla. Jan. 31, 2017).
8. Reginelli v. Boggs, 2018 Pa. LEXIS 1503 (Pa. 2018).
Question: A patient died unexpectedly during hospitalization for a diabetic foot infection. The autopsy revealed the presence of a large saddle pulmonary embolus. The hospital’s peer review committee met to determine if care was suboptimal and whether prophylactic anticoagulation should have been used. When the attending doctor was subsequently sued for malpractice, the plaintiff’s attorney sought to subpoena all of the medical records, including the minutes of the peer review committee. Given this hypothetical scenario, which of the following can occur?
A. “Discovery” is the legal term given to the process during the pretrial phase for amassing relevant documents and other information.
B. A subpoena duces tecum, which is a court order for the production of relevant documents and one that should normally be obeyed, may be issued.
C. The hospital declines to hand over certain types of hospital records, such as peer review minutes, which in this case are statutorily protected from discovery.
D. The plaintiff attorney goes to the judge for an order to compel production and may or may not be successful.
E. All are correct.
Answer: E. Physicians and other participants regularly meet, under strict confidential conditions, to discuss adverse events that occur in their institution. Such records are protected from “discovery,” which is a pretrial procedure for collecting evidence in preparation for trial. The rationale for keeping these records beyond the reach of the discovery process is to encourage participants to engage in candid and free-rein analysis of adverse medical events so as to avoid future mishaps. If the content and nature of these discussions were freely available to parties in litigation, there would be a natural reluctance to express one’s viewpoints in a forthright manner.
Any given state’s statute on discovery requires careful reading because it could differ from another state’s directive – with important legal consequences. As an example, Hawaii’s statute1 contains several inclusions and exclusions and reads in part: “... the information and data protected shall include proceedings and records of a peer review committee, hospital quality assurance committee, or health care review organization that include recordings, transcripts, minutes, and summaries of meetings, conversations, notes, materials, or reports created for, by, or at the direction of a peer review committee, quality assurance committee, or a health care review organization when related to a medical error reporting system. ... Information and data protected from discovery shall not include incident reports, occurrence reports, statements, or similar reports that state facts concerning a specific situation and shall not include records made in the regular course of business by a hospital ... including patient medical records. Original sources of information ... shall not be construed as being immune from discovery ... merely because they were reviewed ... or were in fact submitted to, a health care review organization.”
Predictably, plaintiff attorneys in a medical malpractice lawsuit will attempt to discover information regarding adverse events, hoping to learn about potential errors and judgment lapses, and thus gain an advantage over the defendant doctor and/or hospital. Several recent court cases highlight the contentious nature regarding whether a particular hospital report is to be deemed discoverable. Organized medicine, led by the American Medical Association, has mounted a vigorous response in arguing against the release of peer review and patient safety documents.
The AMA2 recently weighed in on the case of Daley v. Teruel and Ingalls Memorial Hospital. In 2013, a renal failure patient died in an Illinois hospital from injuries that arose from prolonged hypoglycemia. She had received insulin, but when her blood glucose dropped to 16 mg/dl, the treatment team was not alerted and she was later found unresponsive with irreversible brain damage. The issue was whether incident reports from the case that were submitted to a certified PSO (patient safety organization) could be discovered. The Federal Patient Safety and Quality Improvement Act (PSQIA) had created PSOs to aggregate data from multiple sources to reduce adverse events and errors and improve medication safety.
An Illinois lower court ruled that, as part of the discovery process, the hospital had to turn over the report. However, the Illinois Appellate Court ruled in favor of the hospital, holding that the PSQIA protects the report because it is a “patient safety work product.”3 The AMA amicus brief had emphasized that Congress created a safeguarded patient safety process under the PSQIA to encourage hospitals to submit patient safety outcomes without fear of increased liability risk and that “these voluntarily created materials should be used for their intended purpose, not as a roadmap for litigation.”
New Jersey has also ruled against the discovery of a hospital’s self-critical report of a patient’s care, prepared in accordance with New Jersey’s Patient Safety Act.4 The plaintiff alleged that, when she reported to the emergency room at Chilton Medical Center complaining of persistent abdominal pain, fever, body aches, weakness, and a phlegmatic cough, she was incorrectly diagnosed as having pneumonia. In fact, she had appendicitis and a pelvic abscess. The New Jersey Supreme Court affirmed the panel’s order shielding the redacted document from discovery, but it reversed the judgment to the extent it ended the defendants’ discovery obligation with respect to this dispute, requiring instead that the lower court address, through current discovery rules, the proper balancing of interests between requesting and responding parties.
In a recent Michigan case,5 the trial court had earlier ruled that peer review documents at issue were in fact discoverable. Like similar statutes elsewhere, Michigan’s peer review privileges serve to encourage participation to improve on patient morbidity and mortality. The case centered on a court order compelling a Michigan hospital to release a physician’s credentialing file in a medical liability lawsuit on the narrow basis that the nondiscoverability privilege applied only to peer review deliberations and was inapplicable in the case. The trial judge had opined that, if all materials viewed by peer review committees were deemed undiscoverable, a hospital could never be held accountable for any negligent act within the purview of the committee. In its amicus brief in support of the hospital, the AMA argued that Michigan’s peer review privilege has historically spanned the bounds of the actual peer review process, and it countered that hospitals can be held liable – and are regularly held liable – without opening up these documents and that plaintiffs can use the same discovery mechanisms generally available to plaintiffs in other lawsuits.6 The case is currently under appeal.
In contrast, at least two state supreme courts have ruled to limit protections from discovery. The Florida Supreme Court has held that the federal law was intended to improve overall health care rather than to act as a shield to providers. In a case of alleged malpractice with severe neurological injuries, the court took a restrictive interpretation of the PSQIA as it relates to Florida’s risk-management and discovery laws, holding that patient safety work and related reports, when required by state law, do not come under the definition of patient safety work product and were therefore discoverable.7
The Pennsylvania Supreme Court has likewise ruled that documents generated by a hospital’s outside contractor are not protected from discovery under the state’s Peer Review Protection Act. It agreed with a lower-court ruling that Monongahela Valley Hospital could not claim privilege for a performance file on an emergency department physician employed by the hospital’s contractor University of Pittsburgh Medical Center Emergency Medicine.8 The case alleged that the plaintiff’s chest and back pain was misdiagnosed as reflux disease when in fact it was a myocardial infarct.
Dr. Tan is professor of medicine and former adjunct professor of law at the University of Hawaii. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at siang@hawaii.edu.
References
1. Hawaii Revised Statutes §624-25.5 (2012).
2. AMA fights to protect patient-safety work from legal discovery. AMA Morning Rounds. 2018 Aug 1.
3. Daley v. Teruel and Ingalls Memorial Hospital, 2018 Ill. App. LEXIS 440 (Ill. App. Ct. 2018).
4. Brugaletta v. Garcia, 190 A.3d 419 (NJ. 2018).
5. Dwyer v. Ascension Crittenton Hospital. Michigan Supreme Court SC: 158668, 919 N.W.2d 407 (Mi. 2018).
6. Appellate court case puts peer-review protections in danger. AMA Morning Rounds. 2019 Mar 29.
7. Charles v. Southern Baptist Hospital of Florida, Inc., 2017 Fla. LEXIS 231 (Fla. Jan. 31, 2017).
8. Reginelli v. Boggs, 2018 Pa. LEXIS 1503 (Pa. 2018).
Hypertension, white matter hyperintensities, and dementia: What’s the link?
LOS ANGELES – While uncontrolled hypertension is an established risk factor for dementias including Alzheimer’s disease, the pathways by which it might lead to dementia remain poorly understood.
In research presented at the Alzheimer’s Association International Conference, Jérémie Lespinasse, PharmD, an investigator with the University of Bordeaux and INSERM U1219 in Bordeaux, France, presented data showing that hypertension-linked increases in the brain’s load of white matter hyperintensities – an imaging biomarker linked to small-vessel disease – was associated with cognitive decline independent of amyloid cascade biomarkers.
“We know that hypertension is related to cognitive decline and dementia, including Alzheimer’s dementia,” Carole Dufouil, PhD, the study’s last author and the research director at INSERM U1219, said in an interview. “But we didn’t know the pathway. It could go through what’s more typical of vascular pathology or it could go through what’s more typical of AD – and that’s what we wanted to test.”
The researchers found that the impact of hypertension on cognition doesn’t “go through amyloid,” Dr. Dufouil said, but rather a typically vascular pathway of white matter hyperintensities and neurodegeneration. “This is a big difference from other brain markers for which you know they exist, but you don’t know how to treat them,” she said. “This one is treatable.”
For their research, Dr. Lespinasse, Dr. Dufouil, and colleagues used a cross-sectional sample of data from the MEMENTO study, a 5-year observational cohort of 2,323 patients recruited at 26 memory centers in France between 2011 and 2014. Of the patients in MEMENTO, 62% were women, and the mean age was 71. All patients were deemed free of dementia and had isolated cognitive complaints or mild cognitive impairment at baseline. A total of 60% had hypertension, and 17% had uncontrolled hypertension defined as above 140/90 mm Hg despite treatment. Cognitive testing and MRI was conducted on all patients, while 60% also had 18F-fluorodeoxyglucose PET scanning and a minority, 18%, had cerebrospinal fluid samples.
The investigators found in using a structural equation model that the uncontrolled hypertension subjects had significantly lower cognition when compared against those without (P = .001). About half of the harmful effect of uncontrolled hypertension on brain functions was mediated by white matter hyperintensities load (P = .021) and neurodegeneration (P = .024) but not by cerebrospinal fluid biomarkers for amyloid-beta 42/40 ratio or tau.
The study’s main limitation was its use of cross-sectional data, the investigators said, while its strength was in a multifactorial model that allowed for a more integrative look at the relationships among hypertension, Alzheimer’s biomarkers, white matter hyperintensities, and cognition.
The investigators stressed the importance of controlling hypertension generally – and for all clinicians to be more aware of its cognitive impacts. Dr. Dufouil said that memory clinics should make blood pressure monitoring a key part of their workups, and should ensure that people are well controlled. “Up until recently it hasn’t been obvious” that control of hypertension has a key role in dementia prevention.
“It’s now obvious,” she said.
Dr. Lespinasse and Dr. Dufouil disclosed no industry relationships.
LOS ANGELES – While uncontrolled hypertension is an established risk factor for dementias including Alzheimer’s disease, the pathways by which it might lead to dementia remain poorly understood.
In research presented at the Alzheimer’s Association International Conference, Jérémie Lespinasse, PharmD, an investigator with the University of Bordeaux and INSERM U1219 in Bordeaux, France, presented data showing that hypertension-linked increases in the brain’s load of white matter hyperintensities – an imaging biomarker linked to small-vessel disease – was associated with cognitive decline independent of amyloid cascade biomarkers.
“We know that hypertension is related to cognitive decline and dementia, including Alzheimer’s dementia,” Carole Dufouil, PhD, the study’s last author and the research director at INSERM U1219, said in an interview. “But we didn’t know the pathway. It could go through what’s more typical of vascular pathology or it could go through what’s more typical of AD – and that’s what we wanted to test.”
The researchers found that the impact of hypertension on cognition doesn’t “go through amyloid,” Dr. Dufouil said, but rather a typically vascular pathway of white matter hyperintensities and neurodegeneration. “This is a big difference from other brain markers for which you know they exist, but you don’t know how to treat them,” she said. “This one is treatable.”
For their research, Dr. Lespinasse, Dr. Dufouil, and colleagues used a cross-sectional sample of data from the MEMENTO study, a 5-year observational cohort of 2,323 patients recruited at 26 memory centers in France between 2011 and 2014. Of the patients in MEMENTO, 62% were women, and the mean age was 71. All patients were deemed free of dementia and had isolated cognitive complaints or mild cognitive impairment at baseline. A total of 60% had hypertension, and 17% had uncontrolled hypertension defined as above 140/90 mm Hg despite treatment. Cognitive testing and MRI was conducted on all patients, while 60% also had 18F-fluorodeoxyglucose PET scanning and a minority, 18%, had cerebrospinal fluid samples.
The investigators found in using a structural equation model that the uncontrolled hypertension subjects had significantly lower cognition when compared against those without (P = .001). About half of the harmful effect of uncontrolled hypertension on brain functions was mediated by white matter hyperintensities load (P = .021) and neurodegeneration (P = .024) but not by cerebrospinal fluid biomarkers for amyloid-beta 42/40 ratio or tau.
The study’s main limitation was its use of cross-sectional data, the investigators said, while its strength was in a multifactorial model that allowed for a more integrative look at the relationships among hypertension, Alzheimer’s biomarkers, white matter hyperintensities, and cognition.
The investigators stressed the importance of controlling hypertension generally – and for all clinicians to be more aware of its cognitive impacts. Dr. Dufouil said that memory clinics should make blood pressure monitoring a key part of their workups, and should ensure that people are well controlled. “Up until recently it hasn’t been obvious” that control of hypertension has a key role in dementia prevention.
“It’s now obvious,” she said.
Dr. Lespinasse and Dr. Dufouil disclosed no industry relationships.
LOS ANGELES – While uncontrolled hypertension is an established risk factor for dementias including Alzheimer’s disease, the pathways by which it might lead to dementia remain poorly understood.
In research presented at the Alzheimer’s Association International Conference, Jérémie Lespinasse, PharmD, an investigator with the University of Bordeaux and INSERM U1219 in Bordeaux, France, presented data showing that hypertension-linked increases in the brain’s load of white matter hyperintensities – an imaging biomarker linked to small-vessel disease – was associated with cognitive decline independent of amyloid cascade biomarkers.
“We know that hypertension is related to cognitive decline and dementia, including Alzheimer’s dementia,” Carole Dufouil, PhD, the study’s last author and the research director at INSERM U1219, said in an interview. “But we didn’t know the pathway. It could go through what’s more typical of vascular pathology or it could go through what’s more typical of AD – and that’s what we wanted to test.”
The researchers found that the impact of hypertension on cognition doesn’t “go through amyloid,” Dr. Dufouil said, but rather a typically vascular pathway of white matter hyperintensities and neurodegeneration. “This is a big difference from other brain markers for which you know they exist, but you don’t know how to treat them,” she said. “This one is treatable.”
For their research, Dr. Lespinasse, Dr. Dufouil, and colleagues used a cross-sectional sample of data from the MEMENTO study, a 5-year observational cohort of 2,323 patients recruited at 26 memory centers in France between 2011 and 2014. Of the patients in MEMENTO, 62% were women, and the mean age was 71. All patients were deemed free of dementia and had isolated cognitive complaints or mild cognitive impairment at baseline. A total of 60% had hypertension, and 17% had uncontrolled hypertension defined as above 140/90 mm Hg despite treatment. Cognitive testing and MRI was conducted on all patients, while 60% also had 18F-fluorodeoxyglucose PET scanning and a minority, 18%, had cerebrospinal fluid samples.
The investigators found in using a structural equation model that the uncontrolled hypertension subjects had significantly lower cognition when compared against those without (P = .001). About half of the harmful effect of uncontrolled hypertension on brain functions was mediated by white matter hyperintensities load (P = .021) and neurodegeneration (P = .024) but not by cerebrospinal fluid biomarkers for amyloid-beta 42/40 ratio or tau.
The study’s main limitation was its use of cross-sectional data, the investigators said, while its strength was in a multifactorial model that allowed for a more integrative look at the relationships among hypertension, Alzheimer’s biomarkers, white matter hyperintensities, and cognition.
The investigators stressed the importance of controlling hypertension generally – and for all clinicians to be more aware of its cognitive impacts. Dr. Dufouil said that memory clinics should make blood pressure monitoring a key part of their workups, and should ensure that people are well controlled. “Up until recently it hasn’t been obvious” that control of hypertension has a key role in dementia prevention.
“It’s now obvious,” she said.
Dr. Lespinasse and Dr. Dufouil disclosed no industry relationships.
REPORTING FROM AAIC 2019
Nearly 20% of migraineurs use opioids for migraine
PHILADELPHIA – People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.
Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.
To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.
The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.
“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.
Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.
There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.
Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.
Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.
PHILADELPHIA – People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.
Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.
To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.
The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.
“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.
Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.
There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.
Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.
Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.
PHILADELPHIA – People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.
Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.
To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.
The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.
“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.
Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.
There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.
Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.
Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.
EXPERT ANALYSIS FROM AHS 2019
A plurality of migraineurs seeks care from primary care physicians
PHILADELPHIA – according to an investigation presented at the annual meeting of the American Headache Society.
The largest group of these patients consults primary care physicians. The acute and preventive migraine treatment that these patients receive vary according to the type of provider that they see. Nevertheless, treatment is generally suboptimal, compared with the standards of current guidelines, said the investigators.
Migraine is underdiagnosed and undertreated, said Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine, New York, and colleagues. Recent changes in health care policy and the expanded array of treatments for migraine warrant an investigation of the current state of migraine care, they added. They examined survey data to understand where patients with migraine in the United States seek care, which characteristics are associated with seeking care in the previous 12 months, and which treatments are prescribed.
Dr. Buse and colleagues analyzed data from the OVERCOME (Observational Survey of the Epidemiology, Treatment, and Care of Migraine) study. These data were obtained in 2018 using a Web-based survey of a representative U.S. sample of 21,143 patients with migraine. The investigators focused on care seeking and medication use in a subsample of 8,844 patients with 4 or more migraine headache days per month to better understand those with the greatest care needs.
The mean age of this subsample was 42.0 years. Approximately 78% of participants were female, and 74.8% were white. In the preceding 12 months, 61.1% of the patients sought care for migraine; 38.3% sought care from more than two types of provider. Provider types included primary care physicians (45.5%), neurologists (20.2%), emergency medicine clinicians (19.2%), urgent care providers (14.4%), pain specialists (12.8%), headache specialists (12.0%), and retail (nonurgent) clinics (10.4%).
Dr. Buse and colleagues found that sociodemographic factors such as age, sex, education, income, and health insurance type influenced participants’ likelihood of seeking care. Seeking care was positively associated with the number of headache days, pain severity, allodynia, aura, and prodrome. When the researchers examined migraine characteristics, they found that nausea and vomiting (68.8%) was more likely to prompt a patient to seek care, compared with phonophobia and photophobia (64.3%). Participants who sought care from a headache specialist (55.0%) or a neurologist (50.1%) were most likely to be using migraine preventive medication. More than 20% of migraineurs seeking care from primary care, urgent care, or retail clinic professionals were undiagnosed.
Primary care doctors were most likely to prescribe triptans, followed by opioids and preventive medications. Neurologists and headache specialists were most likely to prescribe preventive medications and unlikely to prescribe opioids.
Eli Lilly funds the OVERCOME study. Dr. Buse consults for Lilly on this study, but she and her coauthors who do not work in the industry did not receive any funding for any work related to writing, publishing, or presenting any abstracts, posters, platforms, or manuscripts.
PHILADELPHIA – according to an investigation presented at the annual meeting of the American Headache Society.
The largest group of these patients consults primary care physicians. The acute and preventive migraine treatment that these patients receive vary according to the type of provider that they see. Nevertheless, treatment is generally suboptimal, compared with the standards of current guidelines, said the investigators.
Migraine is underdiagnosed and undertreated, said Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine, New York, and colleagues. Recent changes in health care policy and the expanded array of treatments for migraine warrant an investigation of the current state of migraine care, they added. They examined survey data to understand where patients with migraine in the United States seek care, which characteristics are associated with seeking care in the previous 12 months, and which treatments are prescribed.
Dr. Buse and colleagues analyzed data from the OVERCOME (Observational Survey of the Epidemiology, Treatment, and Care of Migraine) study. These data were obtained in 2018 using a Web-based survey of a representative U.S. sample of 21,143 patients with migraine. The investigators focused on care seeking and medication use in a subsample of 8,844 patients with 4 or more migraine headache days per month to better understand those with the greatest care needs.
The mean age of this subsample was 42.0 years. Approximately 78% of participants were female, and 74.8% were white. In the preceding 12 months, 61.1% of the patients sought care for migraine; 38.3% sought care from more than two types of provider. Provider types included primary care physicians (45.5%), neurologists (20.2%), emergency medicine clinicians (19.2%), urgent care providers (14.4%), pain specialists (12.8%), headache specialists (12.0%), and retail (nonurgent) clinics (10.4%).
Dr. Buse and colleagues found that sociodemographic factors such as age, sex, education, income, and health insurance type influenced participants’ likelihood of seeking care. Seeking care was positively associated with the number of headache days, pain severity, allodynia, aura, and prodrome. When the researchers examined migraine characteristics, they found that nausea and vomiting (68.8%) was more likely to prompt a patient to seek care, compared with phonophobia and photophobia (64.3%). Participants who sought care from a headache specialist (55.0%) or a neurologist (50.1%) were most likely to be using migraine preventive medication. More than 20% of migraineurs seeking care from primary care, urgent care, or retail clinic professionals were undiagnosed.
Primary care doctors were most likely to prescribe triptans, followed by opioids and preventive medications. Neurologists and headache specialists were most likely to prescribe preventive medications and unlikely to prescribe opioids.
Eli Lilly funds the OVERCOME study. Dr. Buse consults for Lilly on this study, but she and her coauthors who do not work in the industry did not receive any funding for any work related to writing, publishing, or presenting any abstracts, posters, platforms, or manuscripts.
PHILADELPHIA – according to an investigation presented at the annual meeting of the American Headache Society.
The largest group of these patients consults primary care physicians. The acute and preventive migraine treatment that these patients receive vary according to the type of provider that they see. Nevertheless, treatment is generally suboptimal, compared with the standards of current guidelines, said the investigators.
Migraine is underdiagnosed and undertreated, said Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine, New York, and colleagues. Recent changes in health care policy and the expanded array of treatments for migraine warrant an investigation of the current state of migraine care, they added. They examined survey data to understand where patients with migraine in the United States seek care, which characteristics are associated with seeking care in the previous 12 months, and which treatments are prescribed.
Dr. Buse and colleagues analyzed data from the OVERCOME (Observational Survey of the Epidemiology, Treatment, and Care of Migraine) study. These data were obtained in 2018 using a Web-based survey of a representative U.S. sample of 21,143 patients with migraine. The investigators focused on care seeking and medication use in a subsample of 8,844 patients with 4 or more migraine headache days per month to better understand those with the greatest care needs.
The mean age of this subsample was 42.0 years. Approximately 78% of participants were female, and 74.8% were white. In the preceding 12 months, 61.1% of the patients sought care for migraine; 38.3% sought care from more than two types of provider. Provider types included primary care physicians (45.5%), neurologists (20.2%), emergency medicine clinicians (19.2%), urgent care providers (14.4%), pain specialists (12.8%), headache specialists (12.0%), and retail (nonurgent) clinics (10.4%).
Dr. Buse and colleagues found that sociodemographic factors such as age, sex, education, income, and health insurance type influenced participants’ likelihood of seeking care. Seeking care was positively associated with the number of headache days, pain severity, allodynia, aura, and prodrome. When the researchers examined migraine characteristics, they found that nausea and vomiting (68.8%) was more likely to prompt a patient to seek care, compared with phonophobia and photophobia (64.3%). Participants who sought care from a headache specialist (55.0%) or a neurologist (50.1%) were most likely to be using migraine preventive medication. More than 20% of migraineurs seeking care from primary care, urgent care, or retail clinic professionals were undiagnosed.
Primary care doctors were most likely to prescribe triptans, followed by opioids and preventive medications. Neurologists and headache specialists were most likely to prescribe preventive medications and unlikely to prescribe opioids.
Eli Lilly funds the OVERCOME study. Dr. Buse consults for Lilly on this study, but she and her coauthors who do not work in the industry did not receive any funding for any work related to writing, publishing, or presenting any abstracts, posters, platforms, or manuscripts.
REPORTING FROM AHS 2019
Alzheimer’s disease raises risk for recurrent seizures
LOS ANGELES – Seizures are not uncommon among patients with Alzheimer’s disease – particularly as patients live longer with the disease – and are often associated with worse cognitive and functional performance, according to research findings presented at the Alzheimer’s Association International Conference.
Jonathan Vöglein, MD, of the German Center for Neurodegenerative Diseases and Ludwig-Maximilian University in Munich presented results from a cohort of 9,127 patients with Alzheimer’s disease (AD), of whom 287 had experienced a seizure, and more than 10,000 non-AD control subjects recruited at clinics during 2005-2016.
Dr. Vöglein and colleagues found that seizure risk increased with duration of disease, from 1.5% of patients at 4.8 years with the disease to 5.4% at 11 years, with likelihood of a seizure increasing steadily over time.
Moreover, 70% of AD patients who experienced a seizure had a second one within 7.5 months. People who had seizures fared worse on cognitive and functional tests: a mean 16.6 on the Mini Mental State Examination, compared with 19.6 for patients without seizures. On a severity rating scale, the Clinical Dementia Rating Sum of Boxes, patients with seizures also fared worse, with scores of 9.3, compared with 6.8 for patients without seizures (P less than .0001 for all, with results adjusted for age and disease duration).
“The data of our study show that there’s an association of seizures with worse cognitive and functional performance,” Dr. Vöglein said in an interview.
“It’s important for clinicians to know that Alzheimer’s patients are at an increased risk for seizures,” Dr. Vöglein said. “In my clinical care experience, seizures are rarely the main complaint of patients with Alzheimer’s disease.” Detailed interviews with the patient and a proxy are important, he added, because patients with Alzheimer’s disease may not always remember events that could be a seizure.
Dr. Vöglein noted that, to his knowledge, there are no reliable data showing that treating seizures with antiepileptic drugs slows cognitive decline. “The results of our study suggest that an antiepileptic treatment after a first seizure in patients with Alzheimer’s dementia may be considered,” he said.
Also at the conference, researcher Ruby Castilla-Puentes, MD, DrPH, of Janssen Pharmaceuticals in Hopewell, N.J., along with Miguel Habeych, MD, MPH, of the University of Cincinnati presented findings on dementia and seizure risk from a large U.S. national managed care database of nearly 3 million people aged 60 years and older, of whom 56% were women.
The researchers analyzed this cohort during 2005-2014 and identified 80,000 people (2.8% of the cohort) as having any dementia diagnosis. The overall incidence of new-onset seizures in patients with dementia was 12.3% per year. In general, all subtypes of seizures and epileptic disorders (partial, generalized, or undifferentiated) occurred more frequently in patients with dementia, compared against patients without dementia (P less than .0001).
People with dementia had more than six times greater risk for experiencing recurring epileptic seizures than did people without dementia (95% confidence interval, 4.4-9.5). They were at six times higher risk for partial seizures (95% CI, 5.5-6.6); fivefold higher risk for generalized (95% CI, 4.9-5.5) and undifferentiated epilepsy (95% CI, 4.8-5.2); and 4.75 times higher risk for generalized seizures (95% CI, 4.5-5.0) and partial epilepsy (95% CI, 4.4-5.1).
“Although there are limitations with the use of administrative claims databases to calculate incidence rates, this analysis suggests that patients of 60 years of age or older have higher risks of new-onset seizures associated with a dementia diagnosis,” Dr. Castilla-Puentes commented.
The findings, she said, reinforce the need for clinicians to monitor for seizures to ensure that patients with dementia receive appropriate treatment.
Dr. Vöglein disclosed no financial conflicts of interest. Dr. Castilla-Puentes disclosed being an employee of Janssen, which funded her study.
LOS ANGELES – Seizures are not uncommon among patients with Alzheimer’s disease – particularly as patients live longer with the disease – and are often associated with worse cognitive and functional performance, according to research findings presented at the Alzheimer’s Association International Conference.
Jonathan Vöglein, MD, of the German Center for Neurodegenerative Diseases and Ludwig-Maximilian University in Munich presented results from a cohort of 9,127 patients with Alzheimer’s disease (AD), of whom 287 had experienced a seizure, and more than 10,000 non-AD control subjects recruited at clinics during 2005-2016.
Dr. Vöglein and colleagues found that seizure risk increased with duration of disease, from 1.5% of patients at 4.8 years with the disease to 5.4% at 11 years, with likelihood of a seizure increasing steadily over time.
Moreover, 70% of AD patients who experienced a seizure had a second one within 7.5 months. People who had seizures fared worse on cognitive and functional tests: a mean 16.6 on the Mini Mental State Examination, compared with 19.6 for patients without seizures. On a severity rating scale, the Clinical Dementia Rating Sum of Boxes, patients with seizures also fared worse, with scores of 9.3, compared with 6.8 for patients without seizures (P less than .0001 for all, with results adjusted for age and disease duration).
“The data of our study show that there’s an association of seizures with worse cognitive and functional performance,” Dr. Vöglein said in an interview.
“It’s important for clinicians to know that Alzheimer’s patients are at an increased risk for seizures,” Dr. Vöglein said. “In my clinical care experience, seizures are rarely the main complaint of patients with Alzheimer’s disease.” Detailed interviews with the patient and a proxy are important, he added, because patients with Alzheimer’s disease may not always remember events that could be a seizure.
Dr. Vöglein noted that, to his knowledge, there are no reliable data showing that treating seizures with antiepileptic drugs slows cognitive decline. “The results of our study suggest that an antiepileptic treatment after a first seizure in patients with Alzheimer’s dementia may be considered,” he said.
Also at the conference, researcher Ruby Castilla-Puentes, MD, DrPH, of Janssen Pharmaceuticals in Hopewell, N.J., along with Miguel Habeych, MD, MPH, of the University of Cincinnati presented findings on dementia and seizure risk from a large U.S. national managed care database of nearly 3 million people aged 60 years and older, of whom 56% were women.
The researchers analyzed this cohort during 2005-2014 and identified 80,000 people (2.8% of the cohort) as having any dementia diagnosis. The overall incidence of new-onset seizures in patients with dementia was 12.3% per year. In general, all subtypes of seizures and epileptic disorders (partial, generalized, or undifferentiated) occurred more frequently in patients with dementia, compared against patients without dementia (P less than .0001).
People with dementia had more than six times greater risk for experiencing recurring epileptic seizures than did people without dementia (95% confidence interval, 4.4-9.5). They were at six times higher risk for partial seizures (95% CI, 5.5-6.6); fivefold higher risk for generalized (95% CI, 4.9-5.5) and undifferentiated epilepsy (95% CI, 4.8-5.2); and 4.75 times higher risk for generalized seizures (95% CI, 4.5-5.0) and partial epilepsy (95% CI, 4.4-5.1).
“Although there are limitations with the use of administrative claims databases to calculate incidence rates, this analysis suggests that patients of 60 years of age or older have higher risks of new-onset seizures associated with a dementia diagnosis,” Dr. Castilla-Puentes commented.
The findings, she said, reinforce the need for clinicians to monitor for seizures to ensure that patients with dementia receive appropriate treatment.
Dr. Vöglein disclosed no financial conflicts of interest. Dr. Castilla-Puentes disclosed being an employee of Janssen, which funded her study.
LOS ANGELES – Seizures are not uncommon among patients with Alzheimer’s disease – particularly as patients live longer with the disease – and are often associated with worse cognitive and functional performance, according to research findings presented at the Alzheimer’s Association International Conference.
Jonathan Vöglein, MD, of the German Center for Neurodegenerative Diseases and Ludwig-Maximilian University in Munich presented results from a cohort of 9,127 patients with Alzheimer’s disease (AD), of whom 287 had experienced a seizure, and more than 10,000 non-AD control subjects recruited at clinics during 2005-2016.
Dr. Vöglein and colleagues found that seizure risk increased with duration of disease, from 1.5% of patients at 4.8 years with the disease to 5.4% at 11 years, with likelihood of a seizure increasing steadily over time.
Moreover, 70% of AD patients who experienced a seizure had a second one within 7.5 months. People who had seizures fared worse on cognitive and functional tests: a mean 16.6 on the Mini Mental State Examination, compared with 19.6 for patients without seizures. On a severity rating scale, the Clinical Dementia Rating Sum of Boxes, patients with seizures also fared worse, with scores of 9.3, compared with 6.8 for patients without seizures (P less than .0001 for all, with results adjusted for age and disease duration).
“The data of our study show that there’s an association of seizures with worse cognitive and functional performance,” Dr. Vöglein said in an interview.
“It’s important for clinicians to know that Alzheimer’s patients are at an increased risk for seizures,” Dr. Vöglein said. “In my clinical care experience, seizures are rarely the main complaint of patients with Alzheimer’s disease.” Detailed interviews with the patient and a proxy are important, he added, because patients with Alzheimer’s disease may not always remember events that could be a seizure.
Dr. Vöglein noted that, to his knowledge, there are no reliable data showing that treating seizures with antiepileptic drugs slows cognitive decline. “The results of our study suggest that an antiepileptic treatment after a first seizure in patients with Alzheimer’s dementia may be considered,” he said.
Also at the conference, researcher Ruby Castilla-Puentes, MD, DrPH, of Janssen Pharmaceuticals in Hopewell, N.J., along with Miguel Habeych, MD, MPH, of the University of Cincinnati presented findings on dementia and seizure risk from a large U.S. national managed care database of nearly 3 million people aged 60 years and older, of whom 56% were women.
The researchers analyzed this cohort during 2005-2014 and identified 80,000 people (2.8% of the cohort) as having any dementia diagnosis. The overall incidence of new-onset seizures in patients with dementia was 12.3% per year. In general, all subtypes of seizures and epileptic disorders (partial, generalized, or undifferentiated) occurred more frequently in patients with dementia, compared against patients without dementia (P less than .0001).
People with dementia had more than six times greater risk for experiencing recurring epileptic seizures than did people without dementia (95% confidence interval, 4.4-9.5). They were at six times higher risk for partial seizures (95% CI, 5.5-6.6); fivefold higher risk for generalized (95% CI, 4.9-5.5) and undifferentiated epilepsy (95% CI, 4.8-5.2); and 4.75 times higher risk for generalized seizures (95% CI, 4.5-5.0) and partial epilepsy (95% CI, 4.4-5.1).
“Although there are limitations with the use of administrative claims databases to calculate incidence rates, this analysis suggests that patients of 60 years of age or older have higher risks of new-onset seizures associated with a dementia diagnosis,” Dr. Castilla-Puentes commented.
The findings, she said, reinforce the need for clinicians to monitor for seizures to ensure that patients with dementia receive appropriate treatment.
Dr. Vöglein disclosed no financial conflicts of interest. Dr. Castilla-Puentes disclosed being an employee of Janssen, which funded her study.
REPORTING FROM AAIC 2019
The expert trap
When you fly as a physician, there’s always a chance you’ll get a free drink. It’s not free, of course. For at least a few minutes, you worked. “Is there a physician onboard? – Ah, just how badly do you want that vodka tonic?
I ring my call button, as I’m sure you do. (It’s worth it to see the flight attendant’s face when I reply: “I’m a dermatologist.”) Last time it was for a 68-year-old man who was vomiting. There was no rash.
I responded along with a pediatrician and an ER nurse – gratitude is an ER nurse at 38,000 feet. The patient had chemotherapy-induced nausea. We three managed to get him well enough to finish the flight. Our ER nurse team member ran the show; she was excellent. She asked all the right questions and helped us all make good decisions. Unlike in clinic, I wasn’t an expert here despite my MD.
Several weeks ago, I saw a patient in the office with severe psoriasis. She stood before me erythrodermic. As I was adjusting her orders, I stepped out of the office to call one of my partners for her opinion. She examined the patient and declared: “I don’t think it’s psoriasis. Despite that biopsy, I think this is chronic eczema.” Brilliant.
In contrast to the former story, I was an expert in my office. And yet, success depended in both instances on my recognizing a cognitive bias: I don’t know everything, and worse, I sometimes don’t realize what I don’t know.
. It’s a common mistake and manifests as overconfidence in our own abilities. For example, what decade did Hawaii join the union? Who is on the 20-dollar bill? Which is the farthest planet? You might be 90% confident of your answers, but most of us are more confident than we ought to be. Chances are you’ll be wrong on one. Recognizing this is hard. And yet, it’s what separates the good from the great clinicians.
Short of having your medical assistant whisper in your ear each day “Memento stultus” (remember you’re stupid), avoiding this bias is difficult. Signs that you might be trapped in an expert mindset are: 1. You believe your patients’ failure to improve is due to lack of adherence to your plan. 2. You cannot recall the last time you tried a new treatment. 3. You never ask others for second opinions. 4. Your colleagues stop asking for your opinion. 5. A flight attendant asks if you would mind returning to your seat rather than help with a medical situation.
If you want to be a better doctor, try working on your sense of self-importance. Remember your limitations and those of medicine. Be methodical in questioning your assumptions. Could you be wrong? Could the data you have be misleading? What are you missing? Ask a colleague to review some of your charts or spend time with you during procedures. Join (or start!) a journal club. Share your difficult cases with others and take note of how their advice differs from your approach.
By recognizing when you might be wrong and humbly stepping aside or taking the time to learn, you might just earn that free drink.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
When you fly as a physician, there’s always a chance you’ll get a free drink. It’s not free, of course. For at least a few minutes, you worked. “Is there a physician onboard? – Ah, just how badly do you want that vodka tonic?
I ring my call button, as I’m sure you do. (It’s worth it to see the flight attendant’s face when I reply: “I’m a dermatologist.”) Last time it was for a 68-year-old man who was vomiting. There was no rash.
I responded along with a pediatrician and an ER nurse – gratitude is an ER nurse at 38,000 feet. The patient had chemotherapy-induced nausea. We three managed to get him well enough to finish the flight. Our ER nurse team member ran the show; she was excellent. She asked all the right questions and helped us all make good decisions. Unlike in clinic, I wasn’t an expert here despite my MD.
Several weeks ago, I saw a patient in the office with severe psoriasis. She stood before me erythrodermic. As I was adjusting her orders, I stepped out of the office to call one of my partners for her opinion. She examined the patient and declared: “I don’t think it’s psoriasis. Despite that biopsy, I think this is chronic eczema.” Brilliant.
In contrast to the former story, I was an expert in my office. And yet, success depended in both instances on my recognizing a cognitive bias: I don’t know everything, and worse, I sometimes don’t realize what I don’t know.
. It’s a common mistake and manifests as overconfidence in our own abilities. For example, what decade did Hawaii join the union? Who is on the 20-dollar bill? Which is the farthest planet? You might be 90% confident of your answers, but most of us are more confident than we ought to be. Chances are you’ll be wrong on one. Recognizing this is hard. And yet, it’s what separates the good from the great clinicians.
Short of having your medical assistant whisper in your ear each day “Memento stultus” (remember you’re stupid), avoiding this bias is difficult. Signs that you might be trapped in an expert mindset are: 1. You believe your patients’ failure to improve is due to lack of adherence to your plan. 2. You cannot recall the last time you tried a new treatment. 3. You never ask others for second opinions. 4. Your colleagues stop asking for your opinion. 5. A flight attendant asks if you would mind returning to your seat rather than help with a medical situation.
If you want to be a better doctor, try working on your sense of self-importance. Remember your limitations and those of medicine. Be methodical in questioning your assumptions. Could you be wrong? Could the data you have be misleading? What are you missing? Ask a colleague to review some of your charts or spend time with you during procedures. Join (or start!) a journal club. Share your difficult cases with others and take note of how their advice differs from your approach.
By recognizing when you might be wrong and humbly stepping aside or taking the time to learn, you might just earn that free drink.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
When you fly as a physician, there’s always a chance you’ll get a free drink. It’s not free, of course. For at least a few minutes, you worked. “Is there a physician onboard? – Ah, just how badly do you want that vodka tonic?
I ring my call button, as I’m sure you do. (It’s worth it to see the flight attendant’s face when I reply: “I’m a dermatologist.”) Last time it was for a 68-year-old man who was vomiting. There was no rash.
I responded along with a pediatrician and an ER nurse – gratitude is an ER nurse at 38,000 feet. The patient had chemotherapy-induced nausea. We three managed to get him well enough to finish the flight. Our ER nurse team member ran the show; she was excellent. She asked all the right questions and helped us all make good decisions. Unlike in clinic, I wasn’t an expert here despite my MD.
Several weeks ago, I saw a patient in the office with severe psoriasis. She stood before me erythrodermic. As I was adjusting her orders, I stepped out of the office to call one of my partners for her opinion. She examined the patient and declared: “I don’t think it’s psoriasis. Despite that biopsy, I think this is chronic eczema.” Brilliant.
In contrast to the former story, I was an expert in my office. And yet, success depended in both instances on my recognizing a cognitive bias: I don’t know everything, and worse, I sometimes don’t realize what I don’t know.
. It’s a common mistake and manifests as overconfidence in our own abilities. For example, what decade did Hawaii join the union? Who is on the 20-dollar bill? Which is the farthest planet? You might be 90% confident of your answers, but most of us are more confident than we ought to be. Chances are you’ll be wrong on one. Recognizing this is hard. And yet, it’s what separates the good from the great clinicians.
Short of having your medical assistant whisper in your ear each day “Memento stultus” (remember you’re stupid), avoiding this bias is difficult. Signs that you might be trapped in an expert mindset are: 1. You believe your patients’ failure to improve is due to lack of adherence to your plan. 2. You cannot recall the last time you tried a new treatment. 3. You never ask others for second opinions. 4. Your colleagues stop asking for your opinion. 5. A flight attendant asks if you would mind returning to your seat rather than help with a medical situation.
If you want to be a better doctor, try working on your sense of self-importance. Remember your limitations and those of medicine. Be methodical in questioning your assumptions. Could you be wrong? Could the data you have be misleading? What are you missing? Ask a colleague to review some of your charts or spend time with you during procedures. Join (or start!) a journal club. Share your difficult cases with others and take note of how their advice differs from your approach.
By recognizing when you might be wrong and humbly stepping aside or taking the time to learn, you might just earn that free drink.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
Changes in sleep-wake timing accompany cerebral glucose hypometabolism and cognitive function
LOS ANGELES – Dysregulated sleep-wake cycles may be linked to cerebral glucose hypometabolism and subtle cognitive changes, both of which are early signs of Alzheimer’s disease–like neurodegeneration, according to a 2-year study of older Korean adults.
The association was particularly strong in subjects who experienced delayed acrophase, the peak of the normal sleep-wake cycle, So-Yeon Jeon, MD, said at the Alzheimer’s Association International Conference. It’s not yet clear whether the changes are a risk factor for dementia or a prodromal sign of neurodegeneration, but even without full elucidation, the findings could have value as a signal of impending neurodegeneration, said Dr. Jeon of Seoul (South Korea) National University.
“Our findings suggest that delayed acrophase may be used as a predictor for the progression of Alzheimer’s-type neurodegeneration and cognitive decline in the near future in old individuals with diverse cognitive status,” she said. “But the relationship between circadian phases and neurodegeneration is complex and not yet well understood.”
The 24-month study comprised 215 elderly adults enrolled in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). They were a mean of 70 years old at baseline; 143 were cognitively normal, 40 had mild cognitive impairment, and 32 had Alzheimer’s dementia. Both at baseline and 2 years, everyone underwent a comprehensive neuropsychological assessment, amyloid PET brain imaging with Pittsburgh compound B, and an [18F]-fluorodeoxyglucose PET scan to determine brain glucose metabolic rate.
Before each assessment, the investigators measured sleep and circadian rhythms with 8 days of actigraphy. This assessed sleep variables (total sleep time, sleep latency, sleep efficiency, and wakefulness after sleep); rest-activity rhythm variables (midline estimated statistic of rhythm, amplitude, and acrophase), and some nonparametric values including interdaily stability, intradaily variability, and relative amplitude of sleep cycles. Subjects also completed sleep diaries during these periods.
The study’s main outcomes were 2-year changes in the Mini Mental State Exam (MMSE) score and in Alzheimer’s imaging biomarkers, including glucose metabolism and amyloid deposition. All analyses controlled for age, sex, Clinical Dementia Rating score, apolipoprotein E allele status, and baseline cognition.
At baseline, lower total sleep time was significantly associated with hypometabolism in areas associated with Alzheimer’s pathology as well as lower mean MMSE scores. Circadian variables showed no significant associations with these characteristics. However, the relative amplitude of circadian rhythm was significantly associated with hypometabolism and with lower MMSE score. There were no associations with brain amyloid load.
At 2 years, acrophase was associated with declines in cerebral glucose metabolism and further changes in the MMSE, even after the researchers controlled for the potential confounders. Delayed acrophase, although not associated with either metabolic rate or cognition at baseline, did significantly influence both at 2 years, suggesting a rapidly eroding clinical picture.
“Neurodegeneration over 2 years means the disease is progressing rapidly and subjects are likely to have tauopathies or other proteinopathy,” Dr. Jeon said. “These pathologies may either be resulting in delayed acrophase followed by neurodegeneration, or they may be prodromal symptoms of impending neurodegeneration. Whether they are early symptoms or early risk factors is not currently known, however. Two years is too short of a follow-up to determine these questions.”
Dr. Jeon had no financial declarations.
SOURCE: Jeon SY et al. AAIC 2019, abstract 33543.
LOS ANGELES – Dysregulated sleep-wake cycles may be linked to cerebral glucose hypometabolism and subtle cognitive changes, both of which are early signs of Alzheimer’s disease–like neurodegeneration, according to a 2-year study of older Korean adults.
The association was particularly strong in subjects who experienced delayed acrophase, the peak of the normal sleep-wake cycle, So-Yeon Jeon, MD, said at the Alzheimer’s Association International Conference. It’s not yet clear whether the changes are a risk factor for dementia or a prodromal sign of neurodegeneration, but even without full elucidation, the findings could have value as a signal of impending neurodegeneration, said Dr. Jeon of Seoul (South Korea) National University.
“Our findings suggest that delayed acrophase may be used as a predictor for the progression of Alzheimer’s-type neurodegeneration and cognitive decline in the near future in old individuals with diverse cognitive status,” she said. “But the relationship between circadian phases and neurodegeneration is complex and not yet well understood.”
The 24-month study comprised 215 elderly adults enrolled in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). They were a mean of 70 years old at baseline; 143 were cognitively normal, 40 had mild cognitive impairment, and 32 had Alzheimer’s dementia. Both at baseline and 2 years, everyone underwent a comprehensive neuropsychological assessment, amyloid PET brain imaging with Pittsburgh compound B, and an [18F]-fluorodeoxyglucose PET scan to determine brain glucose metabolic rate.
Before each assessment, the investigators measured sleep and circadian rhythms with 8 days of actigraphy. This assessed sleep variables (total sleep time, sleep latency, sleep efficiency, and wakefulness after sleep); rest-activity rhythm variables (midline estimated statistic of rhythm, amplitude, and acrophase), and some nonparametric values including interdaily stability, intradaily variability, and relative amplitude of sleep cycles. Subjects also completed sleep diaries during these periods.
The study’s main outcomes were 2-year changes in the Mini Mental State Exam (MMSE) score and in Alzheimer’s imaging biomarkers, including glucose metabolism and amyloid deposition. All analyses controlled for age, sex, Clinical Dementia Rating score, apolipoprotein E allele status, and baseline cognition.
At baseline, lower total sleep time was significantly associated with hypometabolism in areas associated with Alzheimer’s pathology as well as lower mean MMSE scores. Circadian variables showed no significant associations with these characteristics. However, the relative amplitude of circadian rhythm was significantly associated with hypometabolism and with lower MMSE score. There were no associations with brain amyloid load.
At 2 years, acrophase was associated with declines in cerebral glucose metabolism and further changes in the MMSE, even after the researchers controlled for the potential confounders. Delayed acrophase, although not associated with either metabolic rate or cognition at baseline, did significantly influence both at 2 years, suggesting a rapidly eroding clinical picture.
“Neurodegeneration over 2 years means the disease is progressing rapidly and subjects are likely to have tauopathies or other proteinopathy,” Dr. Jeon said. “These pathologies may either be resulting in delayed acrophase followed by neurodegeneration, or they may be prodromal symptoms of impending neurodegeneration. Whether they are early symptoms or early risk factors is not currently known, however. Two years is too short of a follow-up to determine these questions.”
Dr. Jeon had no financial declarations.
SOURCE: Jeon SY et al. AAIC 2019, abstract 33543.
LOS ANGELES – Dysregulated sleep-wake cycles may be linked to cerebral glucose hypometabolism and subtle cognitive changes, both of which are early signs of Alzheimer’s disease–like neurodegeneration, according to a 2-year study of older Korean adults.
The association was particularly strong in subjects who experienced delayed acrophase, the peak of the normal sleep-wake cycle, So-Yeon Jeon, MD, said at the Alzheimer’s Association International Conference. It’s not yet clear whether the changes are a risk factor for dementia or a prodromal sign of neurodegeneration, but even without full elucidation, the findings could have value as a signal of impending neurodegeneration, said Dr. Jeon of Seoul (South Korea) National University.
“Our findings suggest that delayed acrophase may be used as a predictor for the progression of Alzheimer’s-type neurodegeneration and cognitive decline in the near future in old individuals with diverse cognitive status,” she said. “But the relationship between circadian phases and neurodegeneration is complex and not yet well understood.”
The 24-month study comprised 215 elderly adults enrolled in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). They were a mean of 70 years old at baseline; 143 were cognitively normal, 40 had mild cognitive impairment, and 32 had Alzheimer’s dementia. Both at baseline and 2 years, everyone underwent a comprehensive neuropsychological assessment, amyloid PET brain imaging with Pittsburgh compound B, and an [18F]-fluorodeoxyglucose PET scan to determine brain glucose metabolic rate.
Before each assessment, the investigators measured sleep and circadian rhythms with 8 days of actigraphy. This assessed sleep variables (total sleep time, sleep latency, sleep efficiency, and wakefulness after sleep); rest-activity rhythm variables (midline estimated statistic of rhythm, amplitude, and acrophase), and some nonparametric values including interdaily stability, intradaily variability, and relative amplitude of sleep cycles. Subjects also completed sleep diaries during these periods.
The study’s main outcomes were 2-year changes in the Mini Mental State Exam (MMSE) score and in Alzheimer’s imaging biomarkers, including glucose metabolism and amyloid deposition. All analyses controlled for age, sex, Clinical Dementia Rating score, apolipoprotein E allele status, and baseline cognition.
At baseline, lower total sleep time was significantly associated with hypometabolism in areas associated with Alzheimer’s pathology as well as lower mean MMSE scores. Circadian variables showed no significant associations with these characteristics. However, the relative amplitude of circadian rhythm was significantly associated with hypometabolism and with lower MMSE score. There were no associations with brain amyloid load.
At 2 years, acrophase was associated with declines in cerebral glucose metabolism and further changes in the MMSE, even after the researchers controlled for the potential confounders. Delayed acrophase, although not associated with either metabolic rate or cognition at baseline, did significantly influence both at 2 years, suggesting a rapidly eroding clinical picture.
“Neurodegeneration over 2 years means the disease is progressing rapidly and subjects are likely to have tauopathies or other proteinopathy,” Dr. Jeon said. “These pathologies may either be resulting in delayed acrophase followed by neurodegeneration, or they may be prodromal symptoms of impending neurodegeneration. Whether they are early symptoms or early risk factors is not currently known, however. Two years is too short of a follow-up to determine these questions.”
Dr. Jeon had no financial declarations.
SOURCE: Jeon SY et al. AAIC 2019, abstract 33543.
REPORTING FROM AAIC 2019
Huntington’s symptom domains correlate with structural differences
Differences in the prominence of motor, cognitive, and psychiatric symptoms of Huntington’s disease among individuals can be attributed to differences in gray and white matter structural alterations, according to a neuroimaging study of 43 Huntington’s disease gene carriers conducted by Clara Garcia-Gorro, PhD, of the Bellvitge Institute for Biomedical Research and Bellvitge Hospital, Barcelona, and colleagues.
Their work detected a common neurobiological basis for the carriers’ cognitive and motor symptoms in patterns of reductions in gray matter, cortical thickness, and white matter integrity in cognitive and motor networks. They also found that depressive symptoms were associated with imaging findings primarily characterized by reduced cortical thickness in limbic and paralimbic regions.
“These results are relevant in the context of clinical trials, since they could be used to define specific biomarkers for each symptom profile, even before clinical signs appear. Having more homogeneous groups would potentially increase the likelihood of detecting successful interventions and help to find individualized treatments that target specific cognitive, motor, and psychiatric disturbances,” the authors concluded.
SOURCE: Garcia-Gorro C et al. Neuroimage Clin. 2019 Jun 15. doi: 10.1016/j.nicl.2019.101900.
Differences in the prominence of motor, cognitive, and psychiatric symptoms of Huntington’s disease among individuals can be attributed to differences in gray and white matter structural alterations, according to a neuroimaging study of 43 Huntington’s disease gene carriers conducted by Clara Garcia-Gorro, PhD, of the Bellvitge Institute for Biomedical Research and Bellvitge Hospital, Barcelona, and colleagues.
Their work detected a common neurobiological basis for the carriers’ cognitive and motor symptoms in patterns of reductions in gray matter, cortical thickness, and white matter integrity in cognitive and motor networks. They also found that depressive symptoms were associated with imaging findings primarily characterized by reduced cortical thickness in limbic and paralimbic regions.
“These results are relevant in the context of clinical trials, since they could be used to define specific biomarkers for each symptom profile, even before clinical signs appear. Having more homogeneous groups would potentially increase the likelihood of detecting successful interventions and help to find individualized treatments that target specific cognitive, motor, and psychiatric disturbances,” the authors concluded.
SOURCE: Garcia-Gorro C et al. Neuroimage Clin. 2019 Jun 15. doi: 10.1016/j.nicl.2019.101900.
Differences in the prominence of motor, cognitive, and psychiatric symptoms of Huntington’s disease among individuals can be attributed to differences in gray and white matter structural alterations, according to a neuroimaging study of 43 Huntington’s disease gene carriers conducted by Clara Garcia-Gorro, PhD, of the Bellvitge Institute for Biomedical Research and Bellvitge Hospital, Barcelona, and colleagues.
Their work detected a common neurobiological basis for the carriers’ cognitive and motor symptoms in patterns of reductions in gray matter, cortical thickness, and white matter integrity in cognitive and motor networks. They also found that depressive symptoms were associated with imaging findings primarily characterized by reduced cortical thickness in limbic and paralimbic regions.
“These results are relevant in the context of clinical trials, since they could be used to define specific biomarkers for each symptom profile, even before clinical signs appear. Having more homogeneous groups would potentially increase the likelihood of detecting successful interventions and help to find individualized treatments that target specific cognitive, motor, and psychiatric disturbances,” the authors concluded.
SOURCE: Garcia-Gorro C et al. Neuroimage Clin. 2019 Jun 15. doi: 10.1016/j.nicl.2019.101900.
FROM NEUROIMAGE: CLINICAL