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Multiple Factors May Influence Outcomes for Patients With Epilepsy

WASHINGTON, DC—The ability to provide an accurate prognosis for a patient with new-onset epilepsy is crucial for offering him or her the appropriate counseling, according to an overview presented at the 67th Annual Meeting of the American Epilepsy Society.

“Probably the number one question in any patient’s mind is, ‘Am I going to be OK? What’s the chance that this is going to be fine and I’m not really going to have to worry about this?’” said Scott Mintzer, MD, Associate Professor of Neurology at Thomas Jefferson University in Philadelphia.

Scott Mintzer, MD

The literature can offer neurologists guidance in this regard. Despite differing inclusion criteria, lengths of follow-up, and locations, various studies indicate that approximately 68% of patients with epilepsy are in remission at any given time. In addition, two studies found that approximately 60% of patients with epilepsy have permanent remission and that between 20% and 25% of patients are treatment resistant, said Dr. Mintzer. Both of the latter investigations found that between 15% and 20% of patients have a relapsing-remitting course of epilepsy, and approximately half of these people are faring well at any given time.

Epilepsy Syndrome May Influence Prognosis
A patient’s prognosis may depend on his or her epilepsy syndrome. Childhood absence epilepsy “has a reputation for being well controlled,” and the overall outcome for these patients is “excellent,” said Dr. Mintzer. Three studies that examined long-term seizure outcome in patients with childhood absence epilepsy showed that between 72% and 93% of such patients were seizure-free.

The prognosis for patients with juvenile absence epilepsy may not be quite as good, however. Three long-term studies indicate that the rate of seizure freedom among patients with juvenile absence epilepsy ranges between 40% and 60%. All three of the investigations were conducted in Europe and analyzed two-year remission rates.

Two recent studies found that approximately 67% of patients with juvenile myoclonic epilepsy were seizure-free for long periods of time. “I’ve been accustomed to telling people [with juvenile myoclonic epilepsy], ‘You’re not going to be able to come off drugs,’” said Dr. Mintzer. The investigators found, however, that from 10% to 20% of patients could cease their medications.

The prognosis for children with symptomatic generalized epilepsy may be better than has been assumed. In one study, 42% of children with symptomatic generalized epilepsy had a two-year remission. A Finnish study found that two of 14 patients (14%) with symptomatic generalized epilepsy had five-year remission. In another study, 28% of patients with symptomatic generalized epilepsy had five-year remission. On the other hand, the mortality rate for these patients is approximately 24%.

Focal epilepsy syndromes are not always well defined, said Dr. Mintzer. Patients with benign rolandic epilepsy “seem to have an outstanding prognosis,” he added, citing data suggesting that nearly 100% of these patients are seizure-free at five years. Mesial temporal sclerosis generally is considered to require surgery, but several studies indicate that between 25% and 40% of patients with the disease have remission with medication. A recent investigation of cryptogenic focal epilepsy found that 23% of patients with the disease had five-year remission. More data are required “to verify whether that group of patients … is actually that resistant to treatment,” said Dr. Mintzer.

Age at Presentation May Predict Outcome
Clinical factors also appear to predict a patient’s outcome. Investigators in the United Kingdom found that age and the number of seizures at presentation were strong predictive factors. The older the patient was, the less likely he or she was to have problems with seizure control. In addition, the more seizures a patient had at the time of treatment, the less likely he or she was to have remission. “The number of seizures that you have at that point seems to be a strong marker for whether you have bad disease or good disease,” said Dr. Mintzer.

The number of drugs a patient has failed also may predict his or her outcome. Patients who present with new-onset epilepsy and rapidly fail several drugs generally have a low likelihood of becoming seizure-free, said Dr. Mintzer. Recent data suggest that the probability of becoming seizure-free decreases substantially as a patient switches from his or her first drug to his or her fourth drug.

One “curious finding” is that 42% of men and 31% of women achieved the best category of outcome, said Dr. Mintzer. Autoimmune epilepsy could be responsible for this discrepancy, but “we need to see more studies to see if that actually holds up,” he added.

Switching AEDs May Increase Risk of Relapse
Even if a patient becomes seizure-free after beginning treatment with a particular medication, he or she ultimately may need to change medications because of side effects, cost, or, for a female patient, a desire to become pregnant. Researchers have not analyzed whether a patient who is seizure-free on one drug will remain seizure-free after switching to a second drug.

 

 

In an attempt to answer this question, Dr. Mintzer and colleagues examined patients with focal epilepsy who were switched from an enzyme inducer to levetiracetam, lamotrigine, or topiramate. Eligible patients had taken their first drug for at least six months, and the researchers categorized them as being seizure-free or not. Each patient was matched with two control participants who had the same seizure status as the intervention patient but who remained on their original antiepileptic drugs (AEDs). The investigators performed a consecutive, retrospective chart review.

The rate of relapse at six months was 21.7% among patients who were seizure-free at baseline and who subsequently switched AEDs, compared with 4.3% among controls who were seizure-free at baseline and who continued taking their original AEDs. Therefore, switching medication for a seizure-free patient entails an approximately 17% excess risk of recurrent seizure, said Dr. Mintzer.

Among patients who were not seizure-free at baseline and who switched to a new AED, 30% became seizure-free at six months. Among patients who were not seizure-free at baseline and who continued their original AED, 20% became seizure-free at six months. The result indicates that “not everything that happens may be due to drug changes,” said Dr. Mintzer.

The investigators performed statistical comparison adjustment to compensate for differences in the number of drugs failed between the case and control participants. After adjustment, patients who were seizure-free and who switched AEDs had 6.5 times greater odds of relapsing than patients who continued to take the same drug. The result fell short of statistical significance but was “a pretty strong trend,” said Dr. Mintzer. “In the nonseizure-free patients, we were able to demonstrate, as we’d shown in other studies, that the more AEDs you fail, the worse your outcome is likely to be,” he concluded.

—Erik Greb

References

Suggested Reading
Brodie MJ, Barry SJ, Bamagous GA, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78(20):1548-1554.

Kwan P, Brodie MJ. Epilepsy after the first drug fails: substitution or add-on? Seizure. 2000;9(7):464-468.

Luciano AL, Shorvon SD. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol. 2007;62(4):375-381.

Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1000-1015.

Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1016-1026.

Sillanpää M, Shinnar S. Long-term mortality in childhood-onset epilepsy. N Engl J Med. 2010;363(26):2522-2529.

Wang SP, Mintzer S, Skidmore CT, et al. Seizure recurrence and remission after switching antiepileptic drugs. Epilepsia. 2013;54(1):187-193.

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WASHINGTON, DC—The ability to provide an accurate prognosis for a patient with new-onset epilepsy is crucial for offering him or her the appropriate counseling, according to an overview presented at the 67th Annual Meeting of the American Epilepsy Society.

“Probably the number one question in any patient’s mind is, ‘Am I going to be OK? What’s the chance that this is going to be fine and I’m not really going to have to worry about this?’” said Scott Mintzer, MD, Associate Professor of Neurology at Thomas Jefferson University in Philadelphia.

Scott Mintzer, MD

The literature can offer neurologists guidance in this regard. Despite differing inclusion criteria, lengths of follow-up, and locations, various studies indicate that approximately 68% of patients with epilepsy are in remission at any given time. In addition, two studies found that approximately 60% of patients with epilepsy have permanent remission and that between 20% and 25% of patients are treatment resistant, said Dr. Mintzer. Both of the latter investigations found that between 15% and 20% of patients have a relapsing-remitting course of epilepsy, and approximately half of these people are faring well at any given time.

Epilepsy Syndrome May Influence Prognosis
A patient’s prognosis may depend on his or her epilepsy syndrome. Childhood absence epilepsy “has a reputation for being well controlled,” and the overall outcome for these patients is “excellent,” said Dr. Mintzer. Three studies that examined long-term seizure outcome in patients with childhood absence epilepsy showed that between 72% and 93% of such patients were seizure-free.

The prognosis for patients with juvenile absence epilepsy may not be quite as good, however. Three long-term studies indicate that the rate of seizure freedom among patients with juvenile absence epilepsy ranges between 40% and 60%. All three of the investigations were conducted in Europe and analyzed two-year remission rates.

Two recent studies found that approximately 67% of patients with juvenile myoclonic epilepsy were seizure-free for long periods of time. “I’ve been accustomed to telling people [with juvenile myoclonic epilepsy], ‘You’re not going to be able to come off drugs,’” said Dr. Mintzer. The investigators found, however, that from 10% to 20% of patients could cease their medications.

The prognosis for children with symptomatic generalized epilepsy may be better than has been assumed. In one study, 42% of children with symptomatic generalized epilepsy had a two-year remission. A Finnish study found that two of 14 patients (14%) with symptomatic generalized epilepsy had five-year remission. In another study, 28% of patients with symptomatic generalized epilepsy had five-year remission. On the other hand, the mortality rate for these patients is approximately 24%.

Focal epilepsy syndromes are not always well defined, said Dr. Mintzer. Patients with benign rolandic epilepsy “seem to have an outstanding prognosis,” he added, citing data suggesting that nearly 100% of these patients are seizure-free at five years. Mesial temporal sclerosis generally is considered to require surgery, but several studies indicate that between 25% and 40% of patients with the disease have remission with medication. A recent investigation of cryptogenic focal epilepsy found that 23% of patients with the disease had five-year remission. More data are required “to verify whether that group of patients … is actually that resistant to treatment,” said Dr. Mintzer.

Age at Presentation May Predict Outcome
Clinical factors also appear to predict a patient’s outcome. Investigators in the United Kingdom found that age and the number of seizures at presentation were strong predictive factors. The older the patient was, the less likely he or she was to have problems with seizure control. In addition, the more seizures a patient had at the time of treatment, the less likely he or she was to have remission. “The number of seizures that you have at that point seems to be a strong marker for whether you have bad disease or good disease,” said Dr. Mintzer.

The number of drugs a patient has failed also may predict his or her outcome. Patients who present with new-onset epilepsy and rapidly fail several drugs generally have a low likelihood of becoming seizure-free, said Dr. Mintzer. Recent data suggest that the probability of becoming seizure-free decreases substantially as a patient switches from his or her first drug to his or her fourth drug.

One “curious finding” is that 42% of men and 31% of women achieved the best category of outcome, said Dr. Mintzer. Autoimmune epilepsy could be responsible for this discrepancy, but “we need to see more studies to see if that actually holds up,” he added.

Switching AEDs May Increase Risk of Relapse
Even if a patient becomes seizure-free after beginning treatment with a particular medication, he or she ultimately may need to change medications because of side effects, cost, or, for a female patient, a desire to become pregnant. Researchers have not analyzed whether a patient who is seizure-free on one drug will remain seizure-free after switching to a second drug.

 

 

In an attempt to answer this question, Dr. Mintzer and colleagues examined patients with focal epilepsy who were switched from an enzyme inducer to levetiracetam, lamotrigine, or topiramate. Eligible patients had taken their first drug for at least six months, and the researchers categorized them as being seizure-free or not. Each patient was matched with two control participants who had the same seizure status as the intervention patient but who remained on their original antiepileptic drugs (AEDs). The investigators performed a consecutive, retrospective chart review.

The rate of relapse at six months was 21.7% among patients who were seizure-free at baseline and who subsequently switched AEDs, compared with 4.3% among controls who were seizure-free at baseline and who continued taking their original AEDs. Therefore, switching medication for a seizure-free patient entails an approximately 17% excess risk of recurrent seizure, said Dr. Mintzer.

Among patients who were not seizure-free at baseline and who switched to a new AED, 30% became seizure-free at six months. Among patients who were not seizure-free at baseline and who continued their original AED, 20% became seizure-free at six months. The result indicates that “not everything that happens may be due to drug changes,” said Dr. Mintzer.

The investigators performed statistical comparison adjustment to compensate for differences in the number of drugs failed between the case and control participants. After adjustment, patients who were seizure-free and who switched AEDs had 6.5 times greater odds of relapsing than patients who continued to take the same drug. The result fell short of statistical significance but was “a pretty strong trend,” said Dr. Mintzer. “In the nonseizure-free patients, we were able to demonstrate, as we’d shown in other studies, that the more AEDs you fail, the worse your outcome is likely to be,” he concluded.

—Erik Greb

WASHINGTON, DC—The ability to provide an accurate prognosis for a patient with new-onset epilepsy is crucial for offering him or her the appropriate counseling, according to an overview presented at the 67th Annual Meeting of the American Epilepsy Society.

“Probably the number one question in any patient’s mind is, ‘Am I going to be OK? What’s the chance that this is going to be fine and I’m not really going to have to worry about this?’” said Scott Mintzer, MD, Associate Professor of Neurology at Thomas Jefferson University in Philadelphia.

Scott Mintzer, MD

The literature can offer neurologists guidance in this regard. Despite differing inclusion criteria, lengths of follow-up, and locations, various studies indicate that approximately 68% of patients with epilepsy are in remission at any given time. In addition, two studies found that approximately 60% of patients with epilepsy have permanent remission and that between 20% and 25% of patients are treatment resistant, said Dr. Mintzer. Both of the latter investigations found that between 15% and 20% of patients have a relapsing-remitting course of epilepsy, and approximately half of these people are faring well at any given time.

Epilepsy Syndrome May Influence Prognosis
A patient’s prognosis may depend on his or her epilepsy syndrome. Childhood absence epilepsy “has a reputation for being well controlled,” and the overall outcome for these patients is “excellent,” said Dr. Mintzer. Three studies that examined long-term seizure outcome in patients with childhood absence epilepsy showed that between 72% and 93% of such patients were seizure-free.

The prognosis for patients with juvenile absence epilepsy may not be quite as good, however. Three long-term studies indicate that the rate of seizure freedom among patients with juvenile absence epilepsy ranges between 40% and 60%. All three of the investigations were conducted in Europe and analyzed two-year remission rates.

Two recent studies found that approximately 67% of patients with juvenile myoclonic epilepsy were seizure-free for long periods of time. “I’ve been accustomed to telling people [with juvenile myoclonic epilepsy], ‘You’re not going to be able to come off drugs,’” said Dr. Mintzer. The investigators found, however, that from 10% to 20% of patients could cease their medications.

The prognosis for children with symptomatic generalized epilepsy may be better than has been assumed. In one study, 42% of children with symptomatic generalized epilepsy had a two-year remission. A Finnish study found that two of 14 patients (14%) with symptomatic generalized epilepsy had five-year remission. In another study, 28% of patients with symptomatic generalized epilepsy had five-year remission. On the other hand, the mortality rate for these patients is approximately 24%.

Focal epilepsy syndromes are not always well defined, said Dr. Mintzer. Patients with benign rolandic epilepsy “seem to have an outstanding prognosis,” he added, citing data suggesting that nearly 100% of these patients are seizure-free at five years. Mesial temporal sclerosis generally is considered to require surgery, but several studies indicate that between 25% and 40% of patients with the disease have remission with medication. A recent investigation of cryptogenic focal epilepsy found that 23% of patients with the disease had five-year remission. More data are required “to verify whether that group of patients … is actually that resistant to treatment,” said Dr. Mintzer.

Age at Presentation May Predict Outcome
Clinical factors also appear to predict a patient’s outcome. Investigators in the United Kingdom found that age and the number of seizures at presentation were strong predictive factors. The older the patient was, the less likely he or she was to have problems with seizure control. In addition, the more seizures a patient had at the time of treatment, the less likely he or she was to have remission. “The number of seizures that you have at that point seems to be a strong marker for whether you have bad disease or good disease,” said Dr. Mintzer.

The number of drugs a patient has failed also may predict his or her outcome. Patients who present with new-onset epilepsy and rapidly fail several drugs generally have a low likelihood of becoming seizure-free, said Dr. Mintzer. Recent data suggest that the probability of becoming seizure-free decreases substantially as a patient switches from his or her first drug to his or her fourth drug.

One “curious finding” is that 42% of men and 31% of women achieved the best category of outcome, said Dr. Mintzer. Autoimmune epilepsy could be responsible for this discrepancy, but “we need to see more studies to see if that actually holds up,” he added.

Switching AEDs May Increase Risk of Relapse
Even if a patient becomes seizure-free after beginning treatment with a particular medication, he or she ultimately may need to change medications because of side effects, cost, or, for a female patient, a desire to become pregnant. Researchers have not analyzed whether a patient who is seizure-free on one drug will remain seizure-free after switching to a second drug.

 

 

In an attempt to answer this question, Dr. Mintzer and colleagues examined patients with focal epilepsy who were switched from an enzyme inducer to levetiracetam, lamotrigine, or topiramate. Eligible patients had taken their first drug for at least six months, and the researchers categorized them as being seizure-free or not. Each patient was matched with two control participants who had the same seizure status as the intervention patient but who remained on their original antiepileptic drugs (AEDs). The investigators performed a consecutive, retrospective chart review.

The rate of relapse at six months was 21.7% among patients who were seizure-free at baseline and who subsequently switched AEDs, compared with 4.3% among controls who were seizure-free at baseline and who continued taking their original AEDs. Therefore, switching medication for a seizure-free patient entails an approximately 17% excess risk of recurrent seizure, said Dr. Mintzer.

Among patients who were not seizure-free at baseline and who switched to a new AED, 30% became seizure-free at six months. Among patients who were not seizure-free at baseline and who continued their original AED, 20% became seizure-free at six months. The result indicates that “not everything that happens may be due to drug changes,” said Dr. Mintzer.

The investigators performed statistical comparison adjustment to compensate for differences in the number of drugs failed between the case and control participants. After adjustment, patients who were seizure-free and who switched AEDs had 6.5 times greater odds of relapsing than patients who continued to take the same drug. The result fell short of statistical significance but was “a pretty strong trend,” said Dr. Mintzer. “In the nonseizure-free patients, we were able to demonstrate, as we’d shown in other studies, that the more AEDs you fail, the worse your outcome is likely to be,” he concluded.

—Erik Greb

References

Suggested Reading
Brodie MJ, Barry SJ, Bamagous GA, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78(20):1548-1554.

Kwan P, Brodie MJ. Epilepsy after the first drug fails: substitution or add-on? Seizure. 2000;9(7):464-468.

Luciano AL, Shorvon SD. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol. 2007;62(4):375-381.

Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1000-1015.

Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1016-1026.

Sillanpää M, Shinnar S. Long-term mortality in childhood-onset epilepsy. N Engl J Med. 2010;363(26):2522-2529.

Wang SP, Mintzer S, Skidmore CT, et al. Seizure recurrence and remission after switching antiepileptic drugs. Epilepsia. 2013;54(1):187-193.

References

Suggested Reading
Brodie MJ, Barry SJ, Bamagous GA, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78(20):1548-1554.

Kwan P, Brodie MJ. Epilepsy after the first drug fails: substitution or add-on? Seizure. 2000;9(7):464-468.

Luciano AL, Shorvon SD. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol. 2007;62(4):375-381.

Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1000-1015.

Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1016-1026.

Sillanpää M, Shinnar S. Long-term mortality in childhood-onset epilepsy. N Engl J Med. 2010;363(26):2522-2529.

Wang SP, Mintzer S, Skidmore CT, et al. Seizure recurrence and remission after switching antiepileptic drugs. Epilepsia. 2013;54(1):187-193.

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