Posts Tagged epilepsy surgery
Medication can control seizures in about two-thirds of people with epilepsy. The drugs are not a cure, but seizures don’t always last a lifetime; in as many as half of people with epilepsy, the seizures may stop on their own. This means there’s a subset of people taking anti-seizure medication who don’t need it.
After years without seizures, many people want to try stopping their medication. Some of them will stay seizure free, and some won’t.
Predicting who might safely come off medication and who should continue taking it is part science, part art and part personal preference. Some believe that anyone diagnosed with epilepsy should take medication for the rest of their lifetime; others say it’s clear that not all epilepsy is lifelong, and taking unnecessary medication for decades can be a physical, financial and psychological burden.
“There is certainly a group that benefits from medication withdrawal. Who are those patients and how do we identify them?” asked K.P. Vinayan, from the Amrita Institute of Medical Sciences in Kerala. Vinayan spoke during a debate at the ILAE International Congress in Bangkok focused specifically on tapering medication in people with adult-onset focal epilepsy with a known cause.
Alejandro De Marinis, University of Chile, represented the other side of the issue. “We have no idea when we should be taking someone off medication, or even if we should,” he said.
Roadblocks to research
Because of the variety of epilepsy types and patient characteristics, studies on stopping medication tend to combine heterogenous groups. One study might include adult-onset and pediatric onset epilepsy, generalized and focal epilepsy, and adults and children.
Randomized, double-blind studies-;while considered the gold standard of evidence-;are ethically compromising. Both physicians and people with epilepsy generally have strong opinions about whether to continue or stop medication, which could affect compliance. In addition, there’s general agreement that certain subgroups of people with epilepsy need to continue their medication for life.
Only two randomized studies about the effects of stopping medication have been completed; one also was double-blind. That study, known as the Akershus study, found that people whose medication was stopped (through gradual dose tapering) did not have a greater risk for seizures in the following year, compared with people who stayed on their medication. Of the group that stopped medication, 15% had seizures, compared with 7% of the group that continued. But because each group included only about 70 people, statistics showed that the difference in risk could have been due to chance (RR=2.46, 95% CI 0.85-7.08, p=0.095).
The other randomized trial-;a 1991 study of 1,013 adults and children authored by the Medical Research Council (MRC)-;found that stopping medication increased the risk for seizures in the first 2 years: 41% of the group that stopped medication had at least one seizure, compared with 22% of the group that stayed on medication. After that time point, the difference between the groups equalized.
A recent study from China focused specifically on people with adult-onset focal epilepsy. It categorized study participants by seizure-free period: 2 to 3 years, 3 to 4, 4 to 5, and more than 5. Unlike most studies, this one followed participants for up to 15 years after stopping medication.
The research found that people with at least 5 years of seizure freedom before stopping the medication could stop taking medication without an increased risk for seizures. Those with less than 5 years of seizure freedom under their belts were at double to triple the risk for seizures if they stopped their medication, compared with a similar group who stayed on their prescriptions.
In this study, most seizures happened during the first 4 years; in the group with 5 or more years of seizure freedom, most happened during the first 2 years.
As a real-world cohort study lasting more than 10 years, this study provides evidence for patients who would like to consider withdrawing from medications after a long period of seizure freedom.”
Xinshi Wang, First Affiliated Hospital of Wenzhou Medical University
She noted that seizure relapse rates were likely higher in this study than in most others, due to the study population. “Quite a proportion of adult-onset focal epilepsy is caused by focal lesions, whether detectable or undetectable,” said Wang. “This will result in recurrent seizures if the lesions are not removed through surgery.”
Risks and benefits
Study participants were not randomized; they chose whether to stop or continue medication. More than 80% decided to continue treatment. Other studies of patient preference have found similar skews; for example, a survey in Macedonia found that 55% of seizure-free adults preferred to stay on their anti-seizure medication.
“Patients who have been seizure free for a long time are usually tolerant of the drugs they are taking,” said Wang. “And some are afraid that a witnessed seizure would lead to job loss or put them in a dangerous situation.”
Wang said some people in the study may have been reluctant to stop medication because they had risk factors for seizure relapse, such as symptomatic epilepsy or abnormalities on EEG.
On the other hand, some patients may strongly prefer to try stopping their medication, due to side effects, cost, or other issues. This is another reason why clinicians must keep an open mind, said Vinayan, as they need to be involved in the process.
“If their physician is not willing to discuss this option with them, they may try to [stop taking medication] themselves,” she said. “This can be dangerous.”
Who stays seizure free?
Studies have found that between 34% and 88% of patients remained seizure free after stopping medication, which means that 12% to 66% had seizures. The wide range of estimates reflects diverse patient populations, study designs and follow-up times.
Only 15% of people had seizures in the Akershus study; however, that figure comes from the first year of follow-up. The study also had strict criteria that excluded people with certain risk factors for seizure relapse, such as juvenile myoclonic epilepsy or generalized epilepsy with abnormal EEG, as well as anyone taking more than one anti-seizure medication.
Over the years, studies have identified at least 25 factors associated with seizure risk after stopping medication. Eleven are included in an online risk estimator for health professionals. Based on a 2017 meta-analysis, the calculator estimates seizure risk two years and five years after medication is stopped.
Regaining seizure freedom
If seizures are going to recur, research suggests they will do so in the first five years after stopping medication, with about two-thirds of recurrences happening in the first year.
If seizures come back, how easy is it to regain control? Again results vary, due to diverse study populations and varying years of follow-up. A re-analysis of the 1991 MRC data found that 95% regained seizure control at 1 year and 90% at 2 years. A 2005 review of 14 studies found that between 76% and 85% of people could regain seizure freedom after stopping medication. In general, there are people who may need years to regain seizure control, or who may never regain it.
How and why this “acquired drug-resistant epilepsy” happens is still unknown, but certain subgroups appear to be at risk: People whose seizures were difficult to control after diagnosis, people who have been seizure free for a shorter period of time, and people who have focal seizures after stopping medication have all been shown to also have difficulty regaining seizure control.
A lack of seizure control can damage independence and affect driving privileges, employment prospects and overall quality of life.
Continuing medications is a solution that avoids any concerns about re-establishing seizure control, said De Marinis. “Complete seizure control is the best therapeutic measure to improve quality of life,” he said during the debate. “So we should keep people on the drugs.”
However, continued seizure freedom while taking medication is not a guarantee. The two randomized studies saw seizure recurrence rates in people who continued their medication of 7% after 1 year (Akershus) and 22% after 2 years (MRC). Participants in both studies had been seizure free for at least the previous 2 years.
An open question
De Marinis cautioned that any discussion of stopping medication must provide full information and interpretation. “They will need to know the chances of having seizures again, and that there is a chance that if they have seizures, they may no longer be controlled with medication,” he said.
Vinayan concluded that the data support stopping medication in some people; the key is carefully selecting the ones with the lowest risk profile.
“Many of the studies are in very diverse groups, with varying age at epilepsy onset,” he said. Yet they seem to consistently show that after a few years, about half of people who stop taking medication remain seizure free.
“We are not giving half of these people the benefit of coming off their medicine,” Vinayan said. “Because we don’t yet know who they are.”
Epilepsy surgery: A different animal?
Because epilepsy surgery is meant to “cure” seizures, it may seem like a natural next step for someone to stop taking anti-seizure medication after surgery. Though this is generally true for children, some adults remain on medication for years post-surgery, though many end up on tapered doses or fewer drugs.
Clinicians have no randomized trials to guide decisions; trials are done with selected patient cohorts, which “represent a biased sample in which both physicians and patients felt comfortable enough to attempt [medication] withdrawal,” said Lara Jehi in a 2013 commentary .
She suggested that medication withdrawal after surgery may be something like a cardiac stress test for coronary artery disease: A tool to screen for underlying pathology. However, she noted, until randomized controlled studies are done, this “stress test hypothesis” cannot be proven.
A 2015 meta-analysis calculated seizure-free rates of 71% after stopping medication after surgery. But a 2014 critical review estimated that only about 50% of “carefully selected” patients could successfully stop taking medication after temporal lobe surgery, and only about 25% could find success after extra-temporal surgery.
Even good candidates for stopping medication after surgery may prefer not to. A recent study in Denmark found that 3 seizure-free years after surgery, 62% of adults were still taking medication. About one-third were on the same doses and types of medications as before surgery; the rest were on reduced doses. Contacted again 4 years later (7 years after surgery), 18% were still taking medication.
Finding a balance
“For the most part, the decision to maintain the drugs was by the patient’s own wish, and not due to a doctor’s advice,” said study author Anna Stefansdottir, Copenhagen University Hospital.
“Perhaps the surgery allows them to decrease the medication doses and they reach a balance,” she said. “They are seizure free and their side effects have lessened. They’re happy with the results, even if they are still taking medication.”
Fear of relapse was the most commonly cited reason for continuing treatment. Because surgery can bring an end to years of seizures, it’s not surprising, said the authors, that people wouldn’t want to jeopardize that.
“When we discuss surgery, we tell patients that there will be an option to get off the medications,” said Anne Sabers, University of Copenhagen. “But maybe when a patient achieves seizure freedom after surgery, they don’t want to take that risk.”
- Approximately 20% of all epilepsy is caused by acute acquired injury such as traumatic brain injury, stroke and CNS infection, with potential to prevent epilepsy
- No treatment to prevent acquired epilepsy exists; and very few clinical studies have been done during the last 15 years to develop such treatment
- We review possible reasons for this, possible ways to rectify the situations and note some of the ways currently under way to do so
- We further review “cures” of epilepsy that occur spontaneously, and after surgical and sometimes medical antiseizure treatments. We note the limited understanding of the mechanisms of such remissions and thus, at present inability to replicate them with targeted therapy
Vagus nerve stimulation (VNS) was the first neuromodulation device approved for treatment of epilepsy. In more than 20 years of study, VNS has consistently demonstrated efficacy in treating epilepsy. After 2 years, approximately 50% of patients experience at least 50% reduced seizure frequency. Adverse events with VNS treatment are rare and include surgical adverse events (including infection, vocal cord paresis, and so forth) and stimulation side effects (hoarseness, voice change, and cough). Future developments in VNS, including closed-loop and noninvasive stimulation, may reduce side effects or increase efficacy of VNS.
Epilepsy Treatment in Israel
Epilepsy is a spectrum of brain disorders which cause the development of abnormal activity of convulsions. Herzliya Medical Center Private Hospital conducts progressive minimally invasive techniques for the treatment of epilepsy.
What Is Epilepsy
Epilepsy is a disease of the central nervous system, characterized by a violation of the physiological activity of the brain cells. The main manifestation of epilepsy are seizures; the severity, frequency and nature of the disease can vary significantly.
Focal seizures are caused by abnormal activity at one part of the brain. The seizures appear in the form of sensory disorders, a brief loss of consciousness or involuntary contractions of the muscles of the upper or lower limbs. The seizures develop in response to pathological activity of the brain and may be accompanied by falling, twitching muscles and involuntary urination. Brain surgery for epilepsy is done to people to reduce or to stop the number of seizures they have. Surgery for epilepsy involves removing the part of the brain which causes the seizures or separating the part of the brain which causes seizures from the rest of the brain.
A single convulsive seizure is not regarded as a sign of epilepsy. An indication for an in-depth diagnosis is a history of two or more seizures not caused by any objective reasons.
- Neurological examination
- Electroencephalography (EEG). EEG is a graphical recording of the electrical activity of different brain regions. EEG can be performed in the waking state, during sleep, alone or under the influence of a trigger – factor, artificially stimulating seizure activity.
- Computed tomography of the brain (CT). Before planning brain surgery in Israel, neurosurgeons recommend carrying out a CT test; it lets the neurosurgeon visualize the structure of the brain, as well as to diagnose tumors, hemorrhage, cystic formation, against which the patient may develop seizures.
- Magnetic resonance imaging (MRI), both standard and functional. Epilepsy surgery usually requires a functional MRI to determine the areas of the brain that regulate the processes of speech, motor skills and other critical functions.
- Positron emission tomography (PET)
- Single photon emission computed tomography (SPECT). Experts in the field of neurosurgery in Israel recommend having a SPECT scan as well.
Epilepsy Surgery and Treatment in Israel
Treatment of epilepsy usually begins with medication. For most patients, the chronic long-term administration of antiepileptic drugs (AEDs) can reliably control the disease and prevent attacks or significantly reduce their frequency. With the ineffectiveness of drug therapy, a possible epilepsy surgery is considered. The indications for surgery are seizures that occur despite medication. Brain surgery in Israel for the treatment of epilepsy is carried out in cases when the source is located outside the areas of the brain responsible for vital functions: speech, motor skills, vision or hearing.
Surgery may be performed to isolate a certain part of the brain. Neurosurgery in Israel widely uses intraoperative MRI capabilities; during surgery, MRI is used for monitoring to ensure that the impact is applied on the selected area of the brain.
Herzliya Medical Center practices innovative methods of surgical treatment for epilepsy, which is a kind of stereotactic surgery. For the destruction of the convulsive center in the brain a laser beam is used, which causes the heating of tissues and their destruction. The laser beam serves as a thin catheter and is conducted into the cavity of the skull. Minimally invasive laser techniques do not require prolonged hospitalization, the patient can return to normal life within a couple of days.
[WEB SITE] Brain Connectivity Study Could Lead to Better Outcomes for Epilepsy Patients – Health News
The areas in purple are the regions of the brain where connectivity is significantly lower in patients with epilepsy, as compared to well patients.
The different images show the brain data from different angles. Image courtesy of Dario Englot
A new study found that patients with epilepsy have significantly weaker connections throughout their brain, particularly in regions important for attention and cognition, compared to individuals without epilepsy.
These weaker brain connections may reflect harmful long-term effects of recurrent seizures, but importantly the connectivity patterns may be used in the future to help locate which part of the brain is causing seizures, and may help doctors plan more effective surgeries.
In the study, 61 epilepsy patients and 31 controls subjects were analyzed using a non-invasive whole-brain imaging technique that detects magnetic fields produced by the electrical signals in the brain. The technique is called magnetoencephalography, and these MEG signals are used to examine the strength of connections in the brain.
Neurosurgery reisident Dario Englot, MD, PhD, sought to learn what the patterns of brain connectivity in epilepsy patients may tell us about the long-term effects of seizures on the brain. The findings suggest these connectivity patterns could help predict which individuals might benefit most from epilepsy surgery.
Intervening Earlier to Protect the Brain
The researchers found that patients who have had epilepsy for a longer period of time or have more frequent seizures had the most abnormal brain connectivity, suggesting that seizures may have progressive negative effects on the brain over time. This might advocate for early aggressive treatment of epilepsy that is not controlled with medication, to prevent these damaging effects of seizures that accumulate over time.
All patients in the study had seizures that were not controlled despite several anti-epileptic medications, and all ultimately underwent brain surgery to remove the part of the brain causing the seizures. After surgery, about two-thirds of patients became seizure-free. The investigators then examined whether brain connectivity patterns could predict which patients stopped having seizures after surgery.
More Precise Surgeries
Interestingly, those patients who became seizure-free were more likely to have an area of increased connectivity in the part of the brain causing seizures. This was not often seen in individuals who continued to have seizures after surgery. This suggests that although the brain is less connected overall in epilepsy patients, the part of the brain causing seizures may actually have increased connectivity.
Knowing this, MEG studies of brain connectivity could help determine which part of the brain is causing seizures, and may help predict a patient’s chance of becoming seizure-free after epilepsy surgery.
The study, published in the journal Brain, is the product off a multidisciplinary effort at the University of California, San Francisco, including biomedical engineer Srikantan Nagarajan, PhD, neurologist Heidi Kirsch, MD, neurosurgeon Edward Chang, M.D., and several other investigators.
University of California