Epilepsy surgery in India.

Modern epilepsy started in India in 1995 at Sri Chitra Tirunal Institute of Medical Science and Technology, Trivandrum and at All India Institute of Medical Sciences, New Delhi. At both centres the attempt was to get the program going with patients having surgically remediable epilepsy syndromes -who could be evaluated with non invasive investigations. The mainstay of the evaluation was a good quality epilepsy specific MRI and video EEG coupled with a SPECT study and a neuropsychological evaluation. Concordance of the focus on all investigations was critical to a good outcome. There were several problems on the way - but they were managed keeping in consideration our local needs and requirements. Intraoperative electocorticography was done and good outcomes attained. The critical determinants of success were the formation of a team with various interdisciplinary specialists and a strong will to succeed.

Dr. Jakob Chandy, the father of Indian neurosurgery, started the first neurosurgery department in India at Christian Medical College (CMC), Vellore in 1949. He was trained at Montreal Neurological Institute under Dr. Wilder Penfield and also worked for some time with Dr. Theodore Rasmussen. He was joined by Dr. Baldev Singh, a neurologist, a year later who had trained at the National Hospital, Queen Square, London and subsequently studied EEG recordings during epilepsy surgery done by Dr. Percival Bailey. These experiences proved useful in starting the epilepsy surgery program at Vellore. The first epilepsy surgery in India was performed on 25 August, 1952 by Dr. Jakob Chandy with Dr. Baldev Singh reading the EEG on a 19-year-old male with infantile right hemiplegia.[1] This was during a visit by Dr. Penfield to Vellore.

The second department of neurosurgery in India was started in 1950 by Dr. B. Ramamurthi in the city of Madras, about 150 km away from Vellore. He had undergone neurosurgical training in Newcastle, UK, and had also spent some time with Dr. Penfield. He was assisted in EEG by Dr. T.S. Narasimhan and they did their first epilepsy surgery in 1954. In the mid-1960s the Institute of Neurology also applied stereotactic techniques to make lesions in the amygdalo-hippocampal region for temporal lobe epilepsy and in the central median nucleus of the thalamus for generalized seizures.[2] Several hundred epilepsy patients were operated at these two centers in the fifties and sixties.[34] As in the rest of the world, epilepsy surgery fell into disrepute in India also primarily because of poor results from improper localization of epileptic focus.

Better localization of the epileptogenic focus by newer diagnostic tools resulted in the resurgence of epilepsy surgery worldwide in the nineties. In India modern epilepsy surgery started in 1995 at two centers – Sri Chitra Tirunal Institute of Medical Sciences and Technology, Trivandrum (SCTIMST), in south India[5] and at All India Institute of Medical Sciences, New Delhi (AIIMS) in north India.[6] The pattern of revival was very different in the two centers. At Sri Chitra Institute – a dynamic young neurologist - Dr. K. Radhakrishnan had joined after training in the Epilepsy Program at Mayo Clinic. He developed the R. Madhavan Nayar Centre for Comprehensive Epilepsy Care. He was ably assisted by a young neurosurgeon Dr. Malla Bhaskara Rao – who had undergone training in neurosurgery and epilepsy surgery initially with Prof. Ramamurthy and later at various centers. Together they modified the standard protocols to suit the local conditions and established a low cost but effective epilepsy surgery program.[7] They operated their first patient in March 1995 – a patient with mesial temporal sclerosis.

At All India Institute of Medical Sciences, New Delhi, on the other hand no one had any formal training in epilepsy surgery. When the Head of the Neurosurgery Department - Prof. A.K. Banerji asked the author to develop and start epilepsy surgery – the question was what to do? The author was sent for three weeks to Pete Engel, Jr. in UCLA, Los Angeles to “learn” epilepsy surgery. There the author learnt how to form an epilepsy surgery team, how to identify potential cases, how to do a presurgical evaluation, how to conduct an epilepsy surgery conference, and how to counsel the patient and their relatives. The author was also witness to a couple of temporal lobectomies, extratemporal focus resections with electrocorticography, and a corpus callosotomy - Dr. Itzhak Fried was kind enough to show the basics. Three weeks gone by and it was time to go back to India and time for a lot of depression and apprehension! I had been exposed to some state of the art technology – 128 channel video encephalography, ictal SPECT, high-resolution MRI and the PET scan and invasive recordings for a week with subdural grids and depth electrodes. We did not have all these gadgets and could not hope to get them in the near future. How could we ever start? Would it be ethical to start doing epilepsy surgery without all this sophisticated presurgical evaluation? It was a period of despair!

A period of introspection followed. What turned the tide was the concept of “surgically remediable epilepsy” enunciated by Pete Engel. There were a group of syndromes which were inherently resistant to pharmacological treatment and which could be eminently treated by surgery with good outcomes. The classical prototype of this was mesial temporal sclerosis (MTS) – which was the commonest cause of intractable temporal lobe epilepsy. It could be easily diagnosed with a high resolution MRI scan – something that was available in India. We only had to sensitize the radiologist. Hope surfaced! Let us focus on the obvious cases – those with surgically remediable epilepsy syndromes - where extensive workup is not required and where the outcome is likely to be good. Let us forget about the doubtful cases requiring invasive recordings – they could be tackled later. Let us help the large number of patients who have a likely chance to benefit – to free them of the curse of uncontrolled epilepsy. We decided to go ahead and just do it!

An epilepsy surgery team was formed consisting of eight specialists. Dr. Satish Jain - the epileptologist and Dr. Manvir Bhatia - the clinical neurophysiologist were the pillars – absolutely committed and supportive. A comment by a senior that “the initiative was going to be a failure as he had seen several such attempts in the past being abandoned” only strengthened the steely resolve of the core team to succeed. The eight specialists were all young consultants in various disciplines with some common traits - enthusiasm, determination and a desire to succeed at all costs. A conscious decision was taken to treat all the team members as equals and to include all the eight names in any publication or presentation – so that no one could be perceived to be deriving more mileage or benefit than the others. The team remained together over time and continues to be active.

We had a good 1.5 T MRI and soon the neuro-radiologist Dr. Shailesh Gaikwad taught the technicians how to do an epilepsy protocol MRI scan of the head. A video EEG was procured but was put to use only from 9 am to 5 pm – the timings of the Neurophysiology Lab. It was often so frustrating to have a patient taken off the VEEG machine without recording a seizure at 5 pm - only to have a seizure 10 minutes later. An interictal SPECT could be organized by Dr. C. S. Bal - the nuclear medicine expert - but getting an ictal SPECT was not easy. The available neuropsychological battery of tests could not be applied to Indian patients because of differences in language and social background. An Indian battery of test was validated and used by Dr. Surya Gupta - the neuropsychologist. The situation eased somewhat later when space for the VEEG could be arranged in the neurology ward and arrangements made for an ictal SPECT. Now a 24-hour VEEG could be done. Sodium amytal was not available in the Indian pharmacopeia and hence the Wada test could not be done in any patient. It was assumed by us, rightly or wrongly, that if the hippocampus was atrophic and sclerosed enough to cause intractable epilepsy, then it was not good enough to support memory and could be removed without problems.

Therefore, some patients were evaluated, and after discussion in the epilepsy surgery conference, decision was made to operate. The first patient was operated in April 1995. This was a young one and a half-year old girl with very frequent seizures. She had a very unusual CT and MRI scan with a lesion in the medial temporal lobe which was enhancing and also had a dural based component [Figure 1a and b]. At surgery we did a temporal lobectomy and also found an extra-axial lesion along the medial sphenoid ridge. The histopathology [Figure 1c] showed a meningioma with meningio-angiomatosis in the medial temporal lobe – a rare hamartoma. This girl's seizures improved dramatically though the child had significant developmental delay and speech problems which have improved later.[8]

Figure 1a

Contrast CT scan showing left medial temporal lesion with a dural and a parenchymal component

Figure 1b

Contrast MRI of the same patient

Figure 1c

H and E stain showing perivascular whorls of meningioma cells in the cortex – meningio-angiomatosis

In the meantime we acquired some grids and an EEG machine for the operating theatre. We took a decision to do the intraoperative EEG recording in all cases to familiarize ourselves with the recordings and to gain experience of what was normal and what was abnormal - so that when we would be doing extratemporal cases where an electrocorticography (ECog) was critical to the surgery – we would be confident. Alas, our initial attempts to get an intraoperative recording were all singularly unsuccessful. The company engineer was called and he also could not help – no one in the company in India had any experience with ECog earlier. Recordings from the scalp were coming satisfactorily and then we realized that the sensitivity needed to be reduced to accommodate the high voltages and amplitudes from the direct recording from the cortex. Dr. Manvir Bhatia would spend long hours in the operation theatre to do the pre and postexcision recordings. Gradually we gained confidence with the EEG recordings. The other issue was the cost of the subdural grids. They were frightfully expensive and were supposed to be discarded after a single use. The company steadfastly refused to take any responsibility if they were reused. We asked the company how they sterilized the electrodes and they told us that they use ethylene oxide (ETO) sterilization. So we thought if it is good enough for the company to ETO the electrode the first time – then why is it not good enough for us to ETO the electrode the next time. A joint decision was taken by the team that we would reuse the electrodes to cut down costs – without this the program would not have taken off! We routinely reuse our electrodes up to 10-15 times. But we make sure that the electrodes are scrupulously clean and double sterilize them. Did we do the right thing? We think in the interest of the patient – we did!

Coming to the actual surgery, the medial temporal lobe was relatively new. Soon we realized that as neurosurgeons we were usually operating only on the lateral temporal lobe. The anatomy of the medial temporal lobe was partly unknown and much more complex. Repeated reading of the anatomy texts before and after every surgery was done for the first few cases to get a good grasp of the subject and be confident of the surgery. We decided to do an anatomical resection in two parts – the lateral and the medial temporal lobe and not a selective amygdalo – hippocampectomy – as doing that was more difficult technically. We deliberately did not use the ultrasonic suction aspirator so as to get a good anatomical specimen for the pathologist to study. Subpial dissection of the medial temporal lobe structures was learnt and was not as difficult as it sounds - primarily because of the atrophy of the temporal lobe in these cases. The first few specimens were fixed and sectioned in the pathology department only after the author personally demonstrated the orientation of the medial temporal lobe – so that sections could be cut perpendicular to the long axis of the hippocampus. The neuropathologist - Dr. Chitra Sarkar - soon started identifying the subtle changes in the hippocampus architecture – and became proficient in identifying the variety of pathologies found in patients with intractable epilepsy.[9]

The visit by a Canadian epilepsy surgeon Dr. Ramesh Sahjpaul resulted in our learning the technique of awake craniotomy. This was very useful as no special equipment was required compared to motor cortex stimulation or central sulcus mapping using intraoperative SSEP. Very soon the author and the neuro-anesthetist - Dr. H H Dash became comfortable in doing the awake surgery.[10] As neurosurgeons we are used to the patient being absolutely still during surgery and the moment the patient moves we shout out to the anesthetist. In awake craniotomy we have to change our mental attitude and accept movement. The awake patient cannot remain immobile in one position for long and would move when uncomfortable. Rather than getting upset when movement occurs – one should just suspend activities and withdraw instruments the moment the patient moves and restart once they settle down, so the surgeon has to be on the lookout for movement and accept it calmly.

Slowly but steadily we moved forward. Our results were reasonable and the team remained strong. None of us were formally trained – but we learnt and moved ahead as we went along. We overcame the hurdles that we faced and gained confidence and strength. It was a strength gained the hard way – by learning from our mistakes. But we were determined to succeed and succeed we did.

We did not follow Western protocols blindly. They were not practical or doable in our setting. Had we waited till all the infrastructure was in place – we would still be waiting. We needed to customize the protocols to our Indian conditions. We needed to abbreviate the protocols – but it had to be done judiciously so as not to endanger the patient's safety. Our results bore us out.[611]

From April 1995 to June 2002 – we operated 135 patients with intractable epilepsy of which 66 were children. One-third of patients each had epilepsy for less than 5 years, for 5-10 years and more than 10 years respectively. This included 23 patients suffering for more than 15 years. The seizure frequency was less than five seizures per month in a third of patients with another third having seizures daily (including nine patients having more than five seizures per day). Corpus callosotomy was done in 7 patients and 128 patients had focus resection including temporal resections in 98, extratemporal in 29 and hemispherotomy in 1 child. Histopathology revealed mesial temporal sclerosis in 46 patients, DNET in 20, ganglioglioma in 13 patients, glial tumors in 9 and primary cortical dysplasia in 8 patients. One hundred and eleven patients had follow-up from 3 to 77 months with a mean follow-up of 18.5 months. Eighty nine patients (80.2%) are currently seizure free. Thirteen patients had a worthwhile improvement and nine patients (8.1%) had no benefit. These results compare with the best centers of the world.

For the effort to succeed long term we needed to have a bigger team with duplication. We were keenly aware that the epilepsy surgery initiative should not collapse just because a key member of the team leaves for any reason. Therefore we initiated at least two persons for each key area – so that continuity is maintained. Over a period of time all three key anchor persons have left for one reason or the other – but I am happy to say that the initiative goes ahead unhindered under the able leadership of Dr. Sarat Chandra and Dr. Manjari Tripathi. In fact the initiative has only grown stronger and they are doing much larger numbers and more variety of cases than when we started. Furthermore this small initiative has now snowballed into a major effort and has resulted in the development of a centre for epilepsy research with not only clinical disciplines but also a major basic research initiative.

Whatever we achieved was a team effort due to the untiring efforts of one and all – several of whom remain unnamed in this article – and the sheer determination and resolve to make a difference to our patients and their families suffering for a long time from the ravages of intractable epilepsy.

Happily enough, much progress has been made all over India in spreading this movement and popularizing epilepsy surgery. Considering India's vast population there are a large number of patients with surgically remediable syndromes who can benefit significantly with surgery. Various centers are doing epilepsy surgery and doing it well. The undoubted leader is the Centre where it all started – Sri Chitra Tirunal Institute of Medical Sciences and Technology, Trivandrum. They have an excellent Comprehensive Epilepsy Care program which reaches out in the community to provide complete care from primary treatment to state of art invasive recordings and epilepsy surgery. They started off in March 1995 with an anteromedial temporal lobectomy for MTS and were doing mainly temporal resections with noninvasive evaluation till 2001. Subsequently they started electrocorticography, subdural and depth electrode invasive recordings, cortical stimulation, and mapping. They also started doing more extratemporal resections and hemispherotomies. Till date they have operated 1248 patients out of which 280 are children (under 18 years of age). This includes 195 patients with temporal resections, 18 children with extratemporal resections, 45 with hemispherotomy, and 22 with corpus callosotomy.[12] They have achieved excellent outcomes comparable with the best centers of the world and all this has been done at a fraction of the cost abroad. The out of pocket expenses for epilepsy surgery including noninvasive presurgical evaluation has been calculated to be Rs. 50,000 (USD 1200) only. For invasive evaluation and surgery the cost would be two or threefold.[7] Good clinical work is being done by them in various aspects of epilepsy surgery.[13-16]

The next centre of excellence is the All India Institute of Medical Sciences (AIIMS), New Delhi, where the author started the journey a month after SCTIMST started. This centre has operated upon 728 patients of whom 158 are children. The mean age at surgery (for children) was 9.8 years and these children had epilepsy for a mean period of 5.3 years. Temporal resections were the commonest followed by hemispherotomy and extratemporal resections. The follow-up varied from 14 to 112 months with a mean follow-up of 47.3 months. The surgical outcome is given in Table 1. (Data provided by Dr. Sarat Chandra, Dept. of Neurosurgery, AIIMS, New Delhi.)[17] At AIIMS also a lot of good research is being done in various aspects of epilepsy surgery.[18-20]

Table 1

Post operative seizure outcome (excluding corpus callosotomy and VNS)

Epilepsy surgery was done for 87 children following a noninvasive protocol by Jayalakshmi et al.,[21] from Hyderabad with good results – 64.1% were seizure free and 75.6% had a favorable Engel outcome at 32-month follow-up. In adolescents temporal resections were the commonest procedure done in 88.9% cases – mainly for hippocampal sclerosis. In younger children extratemporal resections were more frequent and the lesions were either developmental lesions or tumors.

The gratifying part of this whole exercise has been the interest generated in various centers along the length and breadth of the country. Epilepsy centers have sprung up in various cities – Ludhiana, Chandigarh, Mumbai, Chennai, Vellore, Bangalore, Pune, Kochi, and many more. A lot of good work has been initiated and only promises to grow. However considering the vast population of our country the number of cases that are being done are still miniscule and a lot more needs to be done. We feel that there should be two levels of epilepsy surgery centers. In the first there should be selection of candidates based on noninvasive evaluation only – these would be predominantly patients with surgically remediable epilepsy syndromes. Here one would evaluate patients with intractable epilepsy – get an epilepsy specific MRI scan – subject those with an MRI lesion to VEEG to establish if the lesion is epileptogenic and if the localization is concordant - then subject them to resection. This way we use the MRI to screen patients as MRI scans are relatively more easily available and all that we need to do is to sensitize the radiologist to do an epilepsy specific MRI. We then use the less easily available Video EEG selectively to establish epileptogenesis. The more complicated cases where there is some discordance on noninvasive evaluation could be referred to the second level epilepsy surgery center where facilities for invasive recording would be available. These could be on a regional basis. The epilepsy surgery initiative in our country has gained momentum and we feel that it soon would cover the whole country bringing hope and cheer and a possibility of a cure to the most severely affected children with intractable epilepsy.