Predicting surgery outcomes for epilepsy

This article explains two studies that try to predict surgery outcomes for kids with epilepsy.

Anti-epileptic drugs control seizures and improve quality of life for most people with epilepsy. But for those who find medical treatment ineffective or intolerable, brain surgery is sometimes the next best option. Two studies to be presented at the 68th AES Annual Meeting in December explore the outcomes of brain surgery for children with severe epilepsy.

One study created a decision analysis model to compare how two treatment strategies -medical treatment alone versus brain surgery -- influenced the life expectancy of pediatric patients with refractory epilepsy. Researchers at Boston Children's Hospital developed a decision analysis model with data from the literature. Their findings suggest that surgery increases the odds of a longer life expectancy, compared with medical treatment alone. For example, in a cohort of 10-year old patients, epilepsy surgery in patients with temporal lobe epilepsy yielded 55.2 years of life expectancy, while medical treatment yielded 49.3 years of life expectancy. In extratemporal epilepsy, surgery yielded 54.9 years of life expectancy while medical treatment only yielded 49.3 years. Authors note that the findings suggest that brain surgery is significantly more advantageous than medical treatment alone for eligible children with refractory epilepsy.

A second study examined the effectiveness of resective epilepsy surgery on seizure frequency in children with refractory epilepsy with features of Lennox-Gastaut Syndrome (LGS). Researchers studied 36 patients with LGS who had epilepsy surgery at the Cleveland Clinic for focal, lobar, multilobar resection or hemispherectomy between June 1, 2002 and June 31, 2012. Patients in this study developed epilepsy due to brain lesions or injuries sustained before they were born (17), immediately before or after they were born (10), or between the ages of 2 months and 3 years (9). At the time of surgery, the patients ranged in age from newborn to 18 years, and were experiencing multiple seizures per day.

At follow-up visits conducted 6 months to 6.6 years after surgery, 19 patients were seizure-free. Of the patients still experiencing seizures, two entered late remission 2 years after surgery and five became almost seizure-free, with an average of nine seizures per month. At the last follow-up visit, 24 patients were either seizure-free or had experienced a major reduction in seizure frequency.

"In the past, children with features of Lennox Gastatut syndrome were not considered to be candidates for epilepsy surgery that involves removal of the seizure focus," said Dr. Ahsan Moosa Naduvil, M.D., Staff, section of pediatric epilepsy, Cleveland Clinic Epilepsy Center. "Our study confirms that selected children with early brain lesions may be rendered seizure free with epilepsy surgery."

The authors performed a survival analysis based on the duration of time between seizures, and determined the chance of seizure freedom as 60.1% at 12 months, 51% at 24 months and 40.8% at 30 months or more. According to the authors, the findings suggest that resective epilepsy surgery is an effective treatment option for selected children with LGS secondary to early focal brain lesion or injury.

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Normal life for a person with epilepsy

This article provides much information on epilepsy and describes what an average day is like for a person who has epilepsy.

The roots of epilepsy have been traced as far as 3000 years ago. Because of its disturbing and dramatic features, back then epilepsy was feared and was thought to be a result of some sort of supernatural force or evil influence.

Today we are in the 21st century, yet people with epilepsy are not free from the social stigma, discrimination and isolation. In many rural parts of the country, it is still believed that people with epilepsy are mentally challenged and cannot be treated or lead a normal life. Women with epilepsy face problems in getting married because of the belief that they cannot have children or if they do their children will also be affected. (Read: World Epilepsy Day 2012: Top myths about epilepsy busted)

This clearly shows a lack of understanding of the disorder. Epilepsy doesn’t mean being mentally challenged or having an abnormal life. A person with epilepsy can lead a normal life, get married and have children as well. All you need is a better understanding of the disorder and ways to treat and prevent it.

What is epilepsy?

Epilepsy is a chronic brain condition having unique characteristics. One of the characteristics of people with epilepsy is the recurrence of seizures. That is why epilepsy is commonly known as seizure disorder.

The brain functions with the help of millions of neurons that transmits and receives signals. Epilepsy is caused when the normal pattern of transmission of signals to and from the brain is disturbed. This results in seizures that affect consciousness, body movements and sensations in the affected person for a short period of time until the electric impulses settle. Physical changes that occur during an epileptic seizure may arise either from disturbance in one part of the brain (partial seizure) or in nerve cells from different parts of the brain (generalized seizures). (Read: Epilepsy patients’ brain activity to be monitored)

What is the difference between seizures and epilepsy?

Seizure is just a sign of epilepsy. All patients with epilepsy have seizures but all people having seizures may not have epilepsy. An episode of a single seizure doesn’t indicate that the person is suffering from epilepsy. Seizures can also be triggered by synchronised activity of neurons in the brain occurring in different conditions like high fever, lack of oxygen supply to the brain and hypoglycaemia. Epilepsy is a condition that makes a person susceptible to seizures.

What happens during an epileptic seizure?

Several physical changes take place during an epileptic seizure. Although nothing can describe what the person going through an epileptic attack feels, but the following signs may be seen during an epileptic seizure:

• Sudden jerking movements or twitches in the arm, legs and facial muscles (clonic movements) 
• Rapid movement of the eye balls and head
• Altered consciousness or complete loss of consciousness
• Abdominal discomfort
• Tendency of tongue biting and incontinence.
• Later the patient may feel confused, drowsy and weak

What causes epilepsy?

The exact cause of epilepsy is not found in most cases. Since epilepsy involves the brain function at the neuronal level, several events or conditions that affect the brain may cause epilepsy.

• Trauma to the brain or head injury
• Lack of oxygen supply to the brain during birth
• Brain tumors
• Infections such as meningitis and encephalitis which affect the brain.
• Stroke caused by damage to a blood vessel in the brain
• Neurological diseases such as Alzheimer disease
• Genetic conditions
• Lead poisoning or carbon monoxide poisoning can cause epilepsy
• Drug addiction and overuse of certain antidepressants

Does epilepsy affect a particular age group? Who is at risk?

Dr Arjun Srivatsa, renowned neurosurgeon and founding trustee of Spine Trust India says, ‘Epilepsy is statistically more prevalent in older population. In children, nearly 30 percent of cases are reported in the first 5 years of age. ‘ ‘There is no particular group of people who have greater chances of getting epilepsy,’ he adds further. 

How is epilepsy diagnosed?

According to the Indian Guidelines of Epilepsy, diagnosis of epilepsy requires a detailed medical history of the patient. Dr Srivatsa mentions that epilepsy is usually well described by an eye witness. Therefore, family members and friends of the patient may be required to describe the event and the physical changes observed. The guidelines suggest video recording of the epileptic event can be useful for correct diagnosis.

The doctor will then examine pulse rate and blood pressure of the patient. Presence of subcutaneous nodules and other neurological signs are also examined.

Confirmation of epilepsy is done through various brain imaging procedures. An electroencephalogram (EEG) is a common diagnostic tool used to detect signals from the neurons in the brain and classify the type of epilepsy. The waves resulting from these signals may show a specific pattern which helps the doctor to confirm epilepsy as the cause of seizures. A CT scan or MRI scan may be taken to detect other conditions that may be causing seizures. A positron emission tomography (PET)  scan may be performed to analyze which centers in the brain are involved in seizures. (Read: World Epilepsy Day: Epilepsy more disabling than acknowledged)

How is epilepsy treated? Are there any advances in treatment?

The aim of treatment in epilepsy is to control seizures through anti-epileptic drug (AED) therapy and surgery.

Anti-epileptic drug (AED) therapy: AED is the most common form of treatment given to patients with epilepsy. A single AED (monotherapy) is first given to the patient. Drugs like phenytoin, oxcarbazepine, valproate, phenobarbitone and carbamazepine are conventional drugs used for monotherapy. A combination of these drugs may be given if monotherapy shows no effect on reduction in seizure events. Complete withdrawal of drugs is considered only when the patient is seizure-free. Usually the dosage of drug is reduced gradually and over a period of 3–6 months (or longer) the patient may be free from seizures. Dr Srivatsa says ‘A small group of patients having seizures may need life long medications because of chances of relapse’ (Read: Scientists cure epilepsy in mice) 

Surgery:

‘There is a small population of patients, who do not respond to drug treatments at all. Such patients are termed as refractive to treatment,’ Dr Srivatsa says. ‘However, in such patients, if appropriate diagnosis is done and the areas of the brain which are prone to seizures are mapped using advanced EEG, surgery can be considered,’ he mentions.  

• Removal of seizure focus:It is the most common type of surgery where a small part of the brain where disturbance in signals is observed is removed.
• Multiple Subpial Transection: Sometimes, when the affected part cannot be removed, the surgeon may introduce series of incisions to prevent the signals from the affected part to reach other parts of the brain. 
• Lesionectomy: Epilepsy caused by the presence of a lesion can be treated by surgical removal of the legion.

‘There are newer methods like Vagus nerve stimulation (VNS) which are considered in patients who are not fit for surgeries,’ says  Dr Srivatsa. In this method, a device called vagus nerve stimulator is implanted under the skin of the patient in the chest. The device remains attached to the vagus nerve that delivers electrical signals to the brain thereby reducing seizures by 20-40 percent. 

Diet:

Researchers believe that diet rich in fats and low in carbohydrates (ketogenic diet) may help to reduce the frequency of seizures.

Can epilepsy be prevented? How?

Because the cause of epilepsy is not known, it cannot be prevented. However, childhood epilepsy can be prevented with good care during pregnancy. Genetic screening may help the mother to identify the chances of epilepsy in her child. Preventing head injuries can be taken as a preventive measures since they can lead to epilepsy.

People with epilepsy can control the frequency of their seizures by:

• Adhering to recommended prescribed medication
• Following a regular sleep cycle
• Avoiding stress
• Modifying diet
• Undergoing regular medical checkups and adhering to their follow-up schedule.

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Epilepsy surgery can improve children's behavior and mood

Children who undergo specific types of epilepsy surgery have shown to have their mood and behavior to be substantially improved post-surgery.

Certain types of epilepsy surgery led to significant improvements in children's mood and behavioral problems, a researcher said.

Children undergoing left-side resections were more likely to show neuropsychiatric symptom improvements if the target was in the frontal rather than the temporal lobe, while those having right-side surgeries had improvements irrespective of site, said Elizabeth Andresen, PhD, of theCleveland Clinic's Neurological Institute.

Relatively little improvement was seen in mood or behavioral symptoms in children with left-side temporal lobe seizure foci, but the baseline symptom burden was relatively lower to begin with, she said at a press briefing prior to her platform talk at the annual meeting of the American Epilepsy Society.

Andresen noted that neuropsychiatric complaints are extremely common in children with epilepsy. Previous studies have found a nearly five-fold increase in risk of such disorders in such children compared with the general population, and a 2.5-fold risk increase relative to children with other chronic diseases.

Some other studies have found improvements in such symptoms following epilepsy surgery, she said, but they had not examined whether the benefit varied with the surgical site, either by hemisphere or by lobe.

The study was based on a combination of child self-reports and parental assessments using standard instruments, administered before and after 100 surgeries in pediatric epilepsy patients. Of 54 left hemisphere resections, 38 were in the temporal lobe and 16 in the frontal lobe; of 46 right-sided surgeries, 26 were in the temporal lobe and 20 in the frontal.

At patients' neuropsychological evaluation after surgery, 83% were seizure-free. At last follow-up an average of 5 years after surgery, 57% of the cohort still had not had a recurrence of seizures. Patients were from 5 to 16 years of age (mean 11) at surgery, with mean duration of epilepsy symptoms of 5.3 years (SD 3.6).

In children with left-side resections, normalized T-scores for anhedonia, social anxiety, and withdrawn/depressed symptoms declined significantly for those with frontal lobe targets compared with temporal lobe patients.

• Anhedonia: 59 pre, 50 post in frontal lobe; 50 pre, 50 post in temporal lobe (P=0.009)
• Social anxiety: 59 pre, 42 post in frontal lobe; 49 pre, 48 post in temporal lobe (P=0.001)
• Withdrawn/depressed: 59 pre, 55 post in frontal lobe; 58 pre, 50 post in temporal lobe (P=0.039)

For right-sided surgeries, targets in both lobes were associated with declines in a "social problems" composite. Normalized T-scores for this measure declined from 69 to 64 with frontal lobe procedures and from 59 to 56 with temporal lobe resections (P=0.001 with respect to time and P=0.005 between groups).

Depression was significantly relieved after surgery when Andresen and colleagues analyzed the entire 100-patient cohort. Among the 25 patients rated as depressed prior to surgery, 64% were no longer depressed at follow-up.

Similarly, anxiety resolved in 60% of children with presurgical symptoms, Andresen reported.

She noted that 6% of children who had no symptoms of depression before surgery developed symptoms by the time of follow-up, and 11% of the cohort showed new postsurgical anxiety. But she said rates of emergent depression and anxiety symptoms were similar in a group of epileptic children not undergoing surgery who underwent the same neuropsychological testing.

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Predictors of success of epilepsy surgery

New research uses different factors to determine the potential success of epilepsy surgery.

According to this research, developed by researchers of the UPM, CSIC and the Princesa Hospital, personality style, intelligence quotient and hemisphere of seizure origin are factors that would help to predict successfully these surgeries, what would be helpful for surgeons. Researchers reached these conclusions by using predictive models based on machine learning techniques.

Epilepsy surgery is effective in reducing both number and frequency of seizures, particularly in patients withtemporal lobe epilepsy (TLE). However, a significant proportion of these patients continues suffering seizures after surgery.

In order to have information about the results before surgery, researchers from the Computational Intelligence Group of the Schools of Computing UPM assessed the influence of a battery of medical and psychological factors using predictive models developed from machine learning approaches.

They have identified three "very relevant" elements: the hemisphere of seizure origin, intelligence quotient and personality style (applying the Rorschach test). Researchers have obtained a success rate of 90% in terms of predicting the outcome after surgery by using advanced mathematical models for its combination.

From the researcher's point of view, this study opens the door for integration of complex mathematical models in previous assessment of surgeries. The team of medical assessor will have numerical results about the success of the surgery which are known as decision support tools.

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