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An Operational End to Seizures

Surgery as an option is slowly gaining prominence for a seizure-free life for epileptic patients, says Nayantara Som.

As strange as it may sound, traditional conviction believed that a person suffering from epilepsy was possessed by the devil. Exorcism and incantations were tried 'to drive away the evil spirits', and thus exterminate 'the curse' of epilepsy. In fact, seizures were interpreted as characteristics pertaining to witches and magicians—which is why a wave of persecution and torture was unleashed during the dominance of the Vatican papacy.

From exorcism and witch hunting to medication of anti-epileptic (AEPs) drugs and to the recently used advanced surgeries, treatment for epilepsy has come a long way. Neurologists and neurosurgeons, both on the international and national circuit, are seeking out diverse routes to epileptic treatment. Surgery tops the list in the latest advances because it offers hope of a seizure-free life.

Worldwide statistics for epilepsy are alarming. Nearly one in six of the world population suffer from some form of neurological disorder and 50 million people of the world population are mainly epileptic, and most of them in developing countries. Dr Prithika Chary, Neurosurgeon, Apollo Hospitals, Chennai, gives the Indian scenario and says, "One in 150 of Indians are victims to this disease. This has generated a need for advanced techniques."

Experts also opine a sudden upsurge in awareness in the medical circuit as being responsible for the progress. "As a young medical student, in 12 years, I came across only two cases of epilepsy. Now the number has increased to around 10 cases of epilepsy each day. This is only because of the increasing awareness among patients and doctors who look for more options other than medication," says Dr NC Borah, Neurologist and Founder, GNRC, Guwahati.

This indeed is good news for patients suffering from the disorder, especially for those not responding to medication. Such patients are apt candidates for surgeries that involve either removal of a part of the brain (the focal area for epileptic seizures) or in complicated cases to isolate and disconnect one hemisphere of the brain from the other (to prevent the seizures from spreading to both the hemispheres). "It was presumed there was no cure for epilepsy and that seizures could only be controlled through medication. But surgeries have brought in a complete cure for epilepsy," informs Dr Sangeeta Ravat, Professor and HOD, Department of Neurology, KEM Hospital, Mumbai.

Advanced evaluation tools (from left to right): PET Scan; SPECT Scan; MRI; Video EEG Location Courtesy: Jaslok Hospital

Immune to Medicines

Epileptic seizures mainly occur from a particular part(s) of the brain. It is important that the neurosurgeon zeroes in on the exact spot where the seizure takes place. Ideally, before a neurologist prescribes AEPs, he should be certain about the type of seizure attack the patient experiences. And this is where the predicament begins. Says Dr Paresh Doshi, Functional Neurosurgeon, Jaslok Hospital, Mumbai, "A seizure is a short circuit or a discharge of abnormal electrical activity in the brain. You might ignore it the first time, but the second time it happens, you ought to consult a neurologist for medication." It is also likely that most of the times, the doctors could be unaware about the exact cause of the seizure and blindly prescribe AEPs.

"Modern medications are effective in up to 70 per cent of epileptic patients. Temporal lobe epilepsy and other severe forms of epilepsy are difficult to control with drugs alone," says Dr Dinesh Khandelwal, Consultant Neurologist, Sir Ganga Ram Hospital, New Delhi. Moreover, medication varies with every case. Dr Sandeep Vaishya, Neurologist, Max Super Speciality Hospital, New Delhi, agrees, "Not all patients respond equally well to the AEPs and some studies suggest that up to 25-30 per cent of patients may not respond to the medications at all or may require high doses, so as to cause toxicity of the drug itself." Only after thorough tests and evaluation, can a neurologist decide the right drug and dosage. "In some cases, a wrong drug might be prescribed for the wrong type of seizure. Or a patient might be given an overdose or lesser dose that is not enough to control the seizure. This is when medication is not a good option," elaborates Dr Joy Desai, Consultant Neurologist, Jaslok Hospital, Mumbai.

Patients too can fail to follow up after the initial medication. A survey conducted by GNRC showed that out of 1,000 patients, 70 per cent of the epileptic patients did not take their medication regularly and still many more did not visit their doctors regularly. (see box)

Again, medication is a big 'No' for pregnant women or for those seeking to conceive. "Married women on AEPs are asked not to get pregnant as they are prone to recurrent seizures," adds Jaslok's Dr Doshi. In such a situation, surgery is an option.

Advances: Pre-surgery Stage

While surgical removal of the seizure-prone area of the brain has been in practice for 50 years, it is only in the last few decades that people have begun to accept it. Not all patients are eligible for surgery. A person, who experiences seizure attacks, say every two years, can control it through medication. “Usually, patients experiencing partial or intractable seizures (two to three seizures per week) are eligible candidates for a surgery," adds Dr Doshi. Patients with intractable seizure constitute 20-30 per cent of cases. But the very term 'intractable' needs clearer interpretation. Dr P Sarat Chandra, Associate Professor, Department of Neurosurgery, AIIMS, New Delhi, says, "An intractable seizure is defined as one that cannot be controlled for two years, even after medication. The criterion for distinguishing such patients for surgery is a pre-surgery evaluation." Neurologists and neurosurgeons identify the cause, confirm it, chalk out the safety tips, the function of the area of the brain which is the focal point of the epileptic seizures and categorise ways to remove the part without damaging neighbouring areas.

It is here we see the wonders of technology. Patients are screened and the focal area of epilepsy is detected. Earlier, EEG was the most commonly used diagnostic study in the assessment of patients. Now, with Video EEG, monitoring of habitual seizure has revolutionised the pre-surgical evaluation. "Video EEG correlates clinical behaviour and epileptiform discharges and helps in localisation of epilepsy," says Dr Khandelwal. Patients are hospitalised for three to seven days and AEPs are reduced almost by 30 per cent of the original dose. Trained hospital personnel assess the patients neurologically at the time of seizure. Patients are likely to have multiple seizure attacks due to the reduction in medication. While the video records the reactions and actions of the patient during the seizure, the EEG helps in identifying the focal point of the seizure.

An MRI scanning of the brain has replaced the conventional CT scan because of better resolutions. Other forms of investigations are Positron Emission Tomography (PET) scan and Single Photon Emission Computed Tomography (SPECT), which help in pre-surgical evaluation by localising the epileptic zone. A neuropsychological analysis is done to decipher whether the functionality of the seizure area is intact. Neuropsychological assessments are a battery of tests to measure global intelligence, language, memory and other cognitive faculties. Many hospitals also use the SPECT scan, which works on similar lines as PET. "SPECT scan helps identify a seizure focus," points out Dr Desai. During a seizure, more blood flows through the most active parts of the brain (the seizure focus). A radionuclide is injected. Tissues absorb the radionuclide as it circulates in the blood. A rotating camera picks up photons, the radionuclide particles. This information when transferred to a computer, converts the data onto film. The images are vertical and/or horizontal cross-sections of the body part and can be rendered into 3-D format.

Another advanced method for evaluation is the invasive EEG. This is used when non-invasive Video EEG and neuroimaging fails to delineate the epileptic zone. Here, invasive monitoring is performed with depth or subdural electrodes, which are placed over cortical surface after making burr holes.

A Case Study:Resective surgery

Fig 1 Fig 2 This was a case of a 16-year-old boy, who had seizures since the age of nine and was seizure- free following surgery. Here, a small portion of diseased brain, which serves no other function apart from generating seizures is excised. Fig 1 shows a highly advanced imaging technology, whereby the SPECT images obtained at the time of seizures is coregistered with MR imaging so as to obtain a highly accurate anatomical localisation of the seizure focus. Fig 2 shows the 'epileptogenic' area at surgery. This is further mapped by placing electrical grids on the surface and following further localisation, the abnormal 'epileptogenic' area is removed. Courtesy: Dr P Sarat Chandra

A Case Study : Hemispherotomy

Fig 3 Fig 4 This seven-year-old male child had 150-200 seizures/day. His entire left hemisphere (Fig 3) was diseased and was affected by a condition called Rasmussen's syndrome. He underwent a surgical procedure called Hemispherotomy, whereby his entire left hemisphere was disconnected from the rest of the brain. Fig 4 shows the plane of disconnection without actually removing it. The child became seizure-free and returned back to school after six. Courtesy: Dr P Sarat Chandra

Surgical Advancements

"A seizure is a short circuit or a discharge of abnormal electrical activity in the brain" - Dr Paresh Doshi Functional Neurosurgeon, Jaslok Hospital, Mumbai

Temporal Lobectomy: This involves the removal of the anterior temporal lobe including the medical temporal lobe. "This is the most common and rewarding of all surgeries and can control up to 70-80 per cent of the seizures," points out Dr Doshi. In this method, there are greater chances of patients becoming seizure-free. Dr Vaishya says, "Nearly 60-70 per cent of patients could be seizure free after temporal lobe resection and almost 80-90 per cent of patients can achieve substantial reduction in seizure frequency." Resection includes anterior 3-3.5 cm of inferior and middle temporal gyri, uncus, part of amygdala and the anterior two-three cm of hippocampus and adjacent parahippocampal gyrus. Therefore, more than 85 per cent of patients who have had a temporal lobectomy enjoy a great improvement in seizure. Most patients need to continue taking seizure medicines, but the dosage is reduced.

"A patient might be given an overdose or lesser dose that is not enough to control the seizure. This is when medication is not a good option" - Dr Joy Desai Consultant Neurologist Jaslok Hospital, Mumbai

Extratemporal resection: There are cases when a structural abnormality in the brain, which might be genetic, inherited due to a tumour, vascular malformations or hamartomas situated outside the temporal lobe. Such situations demand performing an extratemporal resection. This involves the removal of the epileptogenic cerebral cortex or lesions outside the anterior temporal lobe. The seizure success rate here is 60-80 per cent. This is an extremely delicate surgery. "Experts are extremely cautious not to damage the main functional element of that area of the brain," points out Dr Desai. A brain mapping or an awake-brain-surgery is conducted to monitor patient movements, language skills, memory power and speech skills. "This is to determine whether the surgery will have an effect on any critical function of the brain," adds Dr Doshi. While the neurosurgeon stimulates the effected part of the brain, the patient is questioned by the speech pathologist or asked to repeat movements. Identification of objects, counting numbers, or slight physical movements are tested. The medical team also uses three-dimensional computer images of the brain taken before and during the surgery as a guide in brain mapping.

Hemispherotomy: Sometimes, merely removing or resurrecting the damaged tissue of the brain is not enough. "There are cases when an entire hemisphere of a brain is epileptic. This usually affects children and they sometimes find themselves paralysed on one side of the body. To avoid the risk of seizures spreading to the other hemisphere (if untouched by abnormal electrical discharges), this affected hemisphere is isolated or totally disconnected from the other side of the brain through a hemispherotomy," says Dr Desai. This surgery is performed on epilepsy associated with major lesions involving one hemisphere. The operation has a short duration and is ideally suited for patients with significant atrophy of the damaged hemisphere. "The most common seizure disorders that respond to this procedure include Rasmussen's encephalitis, Sturge-Weber syndrome, HHE syndrome and hemimegaencephaly," says Dr Doshi. It is necessary that such sensitive surgeries are preferably performed as early as possible in a person's life.

Corpus callosotomy: The corpus callosum connects the right and left cerebral hemisphere. There have been cases when seizures happen across both the hemispheres of the brain. "Sectioning of the corpus callosum disconnects the two hemispheres and prevents the seizures spreading from one hemisphere to the other," adds Dr Ravat. In contrast with lobectomy, corpus callosotomy does not involve removing any brain tissue. Instead, it involves cutting the front two-thirds of this bundle (a procedure called a ‘partial callosotomy’) in the hope that the operation will markedly reduce the frequency. Sometimes, the other one-third is cut later (complete callosotomy). "Corpus callosotomy is utilised for bihemispherical multi-focal epilepsy resulting in frequent generalised seizures; particularly those forms associated with falls and injuries," informs Dr Khandelwal.

Multiple subpial tranaction: If partial seizures occur in an area of the brain that cannot be taken out, multiple subpial transects are an alternative. The surgeon makes a series of shallow cuts into the brain's cerebral cortex, which could interrupt with some fibres that connect the neighbouring parts of the brain. However, chances are they might not cause long-lasting impairment. The concept here is that epileptic discharges propagate tangentially throughout the cortex, whereas the impulses controlling voluntary movement propagate radially. A series of vertical cuts can help control epilepsy and preserve normal functions. Hemispherectomy, corpus callosotmy and multiple subpial transects are palliative procedures to reduce seizure frequency.

Vagus Nerve Stimulation: Vagus nerve stimulation (VNS) can prevent seizures by sending regular, mild pulses of electrical energy to the brain via the vagus nerve. The VNS device is also referred to as a ‘pacemaker for the brain’. It is placed under the skin of the chest wall with a wire running from it to the vagus nerve in the neck. "A small electrode placed around the vagal nerve is connected to a pulse generator implanted in the chest or abdominal wall. The duration of surgery is less than an hour. The technology has been available for over 10 years now and has helped in treating more than 30,000 patients," says Dr Vaishya. VNS is indicated as adjunctive therapy in patients with partial or generalised onset seizure, without age limitation (refractory to AEDs). However, size of device may limit the ability to use VNS in children below three-four years. "Unilateral vocal cord palsy can occur in one per cent, which is temporary. Transient hoarseness of voice and a tingling of the cervical region can occur when an electric impulse is delivered," says Dr Khandelwal.

However, neurosurgeons and neurologists are sceptical of using technique on epileptic patients. Says Dr Chandra, "VNS helps to control the seizures. Though the seizure rate is reduced by 50 per cent in most of the patients, we always tell patients that VNS is like another drug." Dr Vaishya gives another perspective to the success of surgeries altogether. "Almost 30 per cent of patients do not respond well to medication, and about half of them are not the right candidates for surgery or do not respond very well to surgery either," he adds. Moreover, the cost of such a surgery is unaffordable to a majority of people. "While the cost of other epileptic surgeries is anywhere between Rs 25,000- Rs 85,000, a VNS surgery could range from Rs 2 lakh to Rs 5 lakh.

Looking into Your Mind

Epilepsy is the hot topic for myriad research studies across the globe. Recalls Dr Chandra, "At a recent conference for neurosciences in USA, there were around 200-300 papers presented for epilepsy alone.” Currently, it is genetics and nanotechnology that dominates epilepsy research. In nanotechnology, there is a sea of opportunities. One technique, experts predict, is the insertion of nano particles into the body, wherein micro-doses of AEPs are injected. These nano particles attaches itself to the cells — the root cause of seizures. "A usual drug reacts both on the abnormal as well as the normal neurons in the brain. But nanotechnology is devising ways whereby, these nano particles of AEPs will target only the abnormal neurons," points out Dr Chandra. Nanotechnology apart, there is research ongoing in the field of genetics. Dr Ravimohan Rao, Associate Professor, Department of Neurosurgery, Sri Chitra Tirunal Institute of Medical Sciences (SCTIMS), Thiruvananthapuram, says, "Genetic studies will bring about a revolution in treatment methods. There are chromosome studies going on at present in genetics." There is research ongoing in gamma knife surgery whereby, focus radiation (with the help of computers) will zero in on the target area. "Research studies are conducted on the effect of neuroexcitabilty on the affected area after exposure to radiation," adds Dr Rao. Besides, there are myriad drugs in the trial stage and may soon be launched in the Indian market.

Also, till date, experts claim there is lack of knowledge about the exact cause of epileptic attacks. Dr Chary says, "There is research focusing on ion channel disorders for epilepsy." Epilespy might occur due to abnormalities, say in the sodium or potassium channel leading to the brain. AEPs too are likely to cause side effects. "The AEPs, on trial, aims to lessen side effects. There are more than 20 drugs ready to be launched. Deep brain stimulation is also in the trial stage. A method, earlier used for Parkinson's, is now being used for epilepsy. The FDA is yet to give its approval, but human trials have already being conducted in the US and Europe.

A New Hope on the Horizon

The new avenues of treatment for epilepsy offers a whiff of hope to patients forced to lead a restricted lifestyle. "Nearly 60-70 per cent of patient may become seizure-free after temporal lobe resection and almost 80-90 per cent can achieve substantial reduction in seizure frequency. Patients with extratemporal epilepsy, can have their seizure frequency reduced. Fall attacks can be prevented in those with Lennox-Gastaut syndrome with drop attacks by corpus callosotomy," points out Dr Khandelwal.

However, there is apprehension and reluctance from both, patients as well as doctors, towards surgeries. Neurologists and neurosurgeons do not refer patients for surgeries because of the possible risks involved. Besides, the awareness level about surgical options is low in the medical community. With special training courses on the surgical options based abroad, the reluctance of neurologists and neurosurgeons to specialise in epileptic surgeries is another deterrent. Ultimately, the success or failure of an epilepsy surgery depends entirely on the expertise of the team. "A hospital has to have a dedicated neurology team and at the same time the surgical team should be well-trained," adds Rao.

The good news is, there are several hospitals in the country that operate for epilepsy. Hospitals like SCTIMS started performing surgeries for epilepsy since 1994 and have operated on more than 600 patients. Similarly, AIIMS, New Delhi which introduced the surgery 10 years back, has conducted 400 operations that include 25 awake surgeries. More hospitals are likely to introduce these surgeries in the near future.

For instance, Max Super Speciality Hospital, New Delhi is expected to start an epilepsy surgery programme along with the Vagal Nerve stimulation, which is already in practice. GNRC, Guwahati, which at present practises only temporal lobectomy, is soon to introduce other surgical options. With these plans on the cards, it is a positive road ahead for patients.

nayantara.som@expressindia.com