CORPUS CALLOSOTOMY FOR INTRACTABLE SEIZURES: AN INSTITUTIONAL EXPERIENCE

Submitted for MCh Neurosurgery

By

Dr. Rajneesh Misra October 2011

Department of Neurosurgery Sree Chitra Tirunal Institute for Medical Sciences & Technology Thiruvananthapuram – 695011

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CORPUS CALLOSOTOMY FOR INTRACTABLE SEIZURES: AN INSTITUTIONAL EXPERIENCE

Submitted by : Dr.Rajneesh Misra

Programme : MCh Neurosurgery

Month & Year of submission : October 2011

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CERTIFICATE

This is to certify that the thesis entitled “Corpus Callosotomy for intractable seizures: An institutional experience ” is a bonafide work of

Dr. Rajneesh Misra and was conducted in the Department of

Neurosurgery, Sree Chitra Tirunal Institute for Medical Sciences &

Technology, Thiruvananthapuram under my guidance and supervision.

Dr. Suresh Nair Professor and Head Department of Neurosurgery SCTIMST, Thiruvananthapuram

DECLARATION

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This thesis titled “Corpus Callosotomy for intractable seizures: An Institutional experience” is a consolidated report based on a bonafide study done by me during Sep 2009 to Sep 2011 under the Department of Neurosurgery, Sree Chitra Tirunal Institute for

Medical Sciences & Technology, Thiruvananthapuram.

This thesis is submitted to SCTIMST in partial fulfillment of rules and regulations of MCh Neurosurgery examination.

Dr.Rajneesh Misra Department of Neurosurgery, SCTIMST, Thiruvananthapuram.

ACKNOWLEDGEMENT

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My guardian angel, the soul of my late father was with me always guiding and showing me the path of wisdom.

The guidance of Dr. Suresh Nair, Professor and Head of the Department of Neurosurgery, has been invaluable and I am extremely grateful and indebted for his contributions and suggestions, which were a valuable help during the entire work. He will always be a constant source of inspiration to me.

I owe a deep sense of gratitude to Dr.Mathew Abraham &

Dr.George.C.Vilanilam for their invaluable advice, encouragement & guidance, without which this work would not have been possible.

The constant help from Dr. Girish Menon, helped me in achieving a near total follow up of the patients.

I would also like to thank Dr. Easwer H V, Dr. Krishnakumar K, Dr.

Gopalakrishnan C.V, Dr. Vikas & Dr. Jeyanand Sudhir B for their constant encouragement & support.

I would like to acknowledge the help that my colleagues, senior and junior, extended to me during the course of the study.

My sincerest thanks to my wife Sarita who took care of everything else in my life while I was busy with my departmental duties. Without her immense capability to bear with me, nothing would have been possible.

Dr. Rajneesh Misra

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INTRODUCTION

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The history of epilepsy surgery (1) is as old as the origins of modern neurosurgery. Surgical intervention to cure epilepsy can be traced back to reports from France and England of relief of post-traumatic epilepsy by trephination in the early 19th century. Benjamin Winslow Dudley (1785-1870), an american trained among the British was the first one to publish a series of reports of trephination for post-traumatic epilepsy from the Transylvania Medical School in Lexington, Kentucky. Four out of his five patients were relieved of their seizures. Considering the fact that this was a pre-Listerian and pre-anesthesia era ,a success of almost 80% is very impressive . In the late nineteenth century Victor Horsley, a general surgeon by training but with a tremendous interest in neurosurgery (considered the father of epilepsysurgery) reported three craniotomies for focal motor seizures .Two of these patients improved. In association with Hughlings Jackson , he produced milestones in the history of neurosurgery. These included operations on motor cortex, removal of tumor compressing the spinal cord, and so on. While these events were unfolding in the Europe, two epileptologists Frederick and Erna Gibbs at the University of Chicago worked with Percival Bailey to perform temporal lobectomy on patients who were diagnosed to have temporal lobe seizures. Percival Bailey also had a strong influence from European surgeons. The duo that eventually brought epilepsy surgery to the knowledge of common people was Wilder Penf ield and Herbert Jasper. Penfield and Jasper published alandmark book Epilepsy and the Functional Anatomy of the Human Brain in 1954.Herbert Jasper (1906-1999) was born in Oregon

7 | Page and came to Canada in 1938 to build his career at Montreal Neurological Institute as an epileptologist. Interestingly, after this initial excitement, surgical treatment for epilepsy went out of favor for several decades due to high mortality and morbidity of these procedures and availability of effective anti epileptic medications. It was brought into mainstream neurosurgery once again in the 1980s by neurosurgeons in the United States. Modern surgical techniques have placed epilepsy surgery once again as a crucial strategy in management of medically refractory seizures.

Epilepsy Surgery in India (2) The first epilepsy surgery in India was performed at CMC , Vellore on 25 Aug 1952 by Prof Jacob Chandy on a 19 year old male from cenrtal Kerala who had intractable seizures with infantile hemiplegia. Though the boy died of meningitis 9 days after the procedure, it is generally considered to herald the start of modern epilepsy surgery in India. In the decades of 1950- 60 and 1960-70 several epilepsy surgeries were performed at CMC, Vellore and Institute Of Neurology ,Madras. In 1970’s , there was decline in epilepsy surgeries partly because the two pioneering stalwarts in the fields ( Prof Jacob Chandy and Prof B Ramamurthi) retired from active service. There was a resurgence of epilepsy surgery with establishment of R Madhavan Nair Centre for comprehensive epilepsy care at The SCTIMST ,Trivandrum due to the efforts of Prof K.Radhakrishnan ,a renowned neurologist trained at Mayo Clinic , Rochester, Minnesota ,USA. The first anterior temporal lobectomy and amygdalohippocampectomy at SCTIMST

8 | Page was performed on March 20 ,1995 by Dr Mallabhaskar Rao on a 25 year old male with left MTS. Since then, more than 1300 procedures have been performed at SCTIMST including 23 corpus callosotomies. The present study aims to summarise this Institute’s experience with corpus callosotomy for medically refractory seizures.

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REVIEW OF LITERATURE

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INCIDENCE OF EPILEPSY Total Population Studies There are relatively few studies of incidence of epilepsy in the society. In developed countries, the age-adjusted incidence of epilepsy (recurrent unprovoked seizures) ranges from 24 to 53 per 100,000 person- years.(3-8) Total population studies reporting the incidence of a first diagnosis of unprovoked seizures (differing from incidence of epilepsy by the inclusion of persons with a single unprovoked seizure as well as those with recurrent unprovoked seizures) provides estimates of incidence ranging from 26 to 70 per 100,000 person-years (Table 1). Given methodologic differences, the incidence in studies of predominantly Western, industrialized countries seems remarkably consistent across geographic areas. This seems particularly true of reports for the last two decades (1990 to 2010). Table 1

Reference Publication Region Population/person- Number Age-adjusted date years of cases (U.S. 2000 census) Tekle- 1997 Ethiopia 215,901 139 43 Haimanot(9) Annegers et 1999 Texas 601,448 197 28 al.(3) MacDonald 2000 England 100,230 69 79 et al.(10) Olafsson et 2005 Iceland 882,151 501 52a al.(11) a All unprovoked seizures

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Some studies provide incidence from developing countries. An incidence of epilepsy that is considerably higher than that reported in industrialized countries (114 per 100,000 person-years) has been reported from a rural area of Chile(10). A study in Tanzania(12) reported the incidence of epilepsy to be 77 per 100,000. These are two to three times the incidence reported in industrialized countries in which similar definitions have been used. A large population-based survey in Ecuador by Placencia et al in 1992 (13) identified all individuals with a history of seizures. Included were all persons with newly occurring nonfebrile seizures (including acute symptomatic seizures) and some children with multiple febrile seizures. Because of the broader case-inclusion criteria in this study and uncertainty regarding age-specific distribution and cause of acute symptomatic seizures, there is no way to compare these incidence studies.

Age-specific Incidence The incidence of epilepsy is clustered in the young and elderely (Fig. 1 and 2), at least in industrialized countries. Age-specific incidence is consistently high in the youngest age groups, with highest incidence occurring during the first few months of life. Incidence falls dramatically after the first year of life, seems relatively stable through the first decade of life, and falls again during adolescence.(14) In developed countries, the incidence of epilepsy is higher after the age of 70 years than during the first 10 years of life. Only about 50% of cases of epilepsy start in childhood or adolescence.

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Fig 1. Age specific incidence of Epilepsy in developed countries

Fig 2 .Age specific incidence of epilepsy in developing world

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Seizure Type Seizure-specific incidence or proportions of cases with a specific seizure type based on the International Classification of Epileptic Seizures are provided in several contemporary incidence studies .A detailed distribution from the Iceland study (11) is provided in Figure 3.(NOS =Not otherwise specified)

Fig 3 .Distribution of seizure type in Iceland incidence cases, 1995- 1999.

Race Most total population incidence studies have been performed in white populations of European extraction. Even in studies of incidence in Asian or African populations, study groups have been homogeneous. Racial differences have been examined only in incidence or cohort studies in children. In the National Collaborative Perinatal Project,(15) incidence of

14 | Page afebrile seizures did not differ across racial groups through the age of 7 years.

Epileptic Syndromes

There are a few total population incidence studies that present the distribution of epilepsy syndromes such as the study conducted in Bordeaux,(16) and studies from Iceland.(14) In Bordeaux, the incidence of idiopathic localization-related epilepsy was 1.7 per 100,000 (7% of all cases). An additional 13.6 per 100,000 (56%) had symptomatic localization-related epilepsy. Thus, if the same criteria are used as in most other contemporary incidence studies, about 60% of cases can be classified as partial seizures. Each of the following syndromes accounted for about 1% of new cases: Juvenile myoclonic epilepsy, awakening grand mal, and West syndrome. About 2% had pyknolepsy. These proportions are similar to those provided by the Rochester, Minnesota, studies.(50)

Etiology of Epilepsy in Incidence Cohorts Most of the population-based incidence studies provide information regarding presumed etiology. (3,8,10).Rarely have definitions for inclusion been provided, but the proportion of cases with an identified antecedent (remote symptomatic epilepsy) is relatively consistent, ranging from 23% to 39%(50)(Fig. 4). In children, epilepsy associated with neurologic deficits from birth seems to be the most important single etiologic relationship, whereas

15 | Page cerebrovascular disease is the most commonly identified cause among adults.

Fig 4 Age of onset attributable to various antecedents

Classic Risk Factors Head (brain) trauma, stroke, central nervous system infection, and degenerative brain disease are frequently identified.(17,18) Specific causes of epilepsy may differ across geographic areas, but whether incidence studies are undertaken in developing countries or in developed countries, a definitive etiology has been identified in only about one third of all newly diagnosed cases. In industrialized countries, cerebrovascular disease is the most frequently identified cause of epilepsy, accounting for about 12% of all new cases and about one third of cases with an identified cause (Fig. 5). In South America, the most frequently identified cause is infection of the

16 | Page central nervous system. In developing and developed countries, cerebral palsy is associated with a large proportion of cases, particularly in children. In incidence studies in endemic areas, neurocysticercosis accounts for about 10% of newly diagnosed cases of epilepsy, confirming the importance of this factor.

Fig 5 Classic risk Factors

Risk Factors Identified in Epidemiologic Studies Epidemiologic studies have not only confirmed the importance of postnatal insults, but also qualified the risk. As shown in Figure 6, a risk ratio of 1 implies no increase in risk, a risk ratio of <1 suggests a protective effect, and a risk ratio of >1 suggests an increase in risk.

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The risk for epilepsy among persons with penetrating head injuries acquired during military service was more than 500 times that expected in the general population.(18) In contrast, individuals who have had brain injuryassociated with loss of consciousness or amnesia of <30 minutes' duration have no increase in risk.(16) Studies have also identified other factors (drug and alcohol abuse, depressive illness, suicidality, migraine with aura, hypertension, and risk factors for stroke) that increase the risk for epilepsy at times as much as or more than the classic risk factors (19,20)

Fig 6 Change in risk for epilepsy in association with specific antecedents. ADD, Attention deficit disorder; HD, hyperactivity disorder; LVH, left ventricular Hypertrophy

Family History as Risk Factors A small proportion of cases of epilepsy may be attributable to single-gene

18 | Page disorders. In two syndromes with mendelian inheritance patterns, a chromosomal localization has been achieved. Benign familial neonatal convulsions with a dominant inheritance pattern was initially localized to chromosome 20 (21) but genetic heterogeneity has been demonstrated by a more recent localization to chromosome 8. (22) A gene for progressive myoclonic epilepsy has been localized to chromosome 21. (23)

PREVALENCE OF EPILEPSY

Prevalence is more a reflection of survival and severity or chronicity of illness than of frequency of illness. Little reliable information regarding etiology or prognosis can be derived from prevalence studies, although they can provide intriguing clues to guide hypotheses that can be tested in properly designed studies. Prevalence data are primarily of value in planning for health care.

Fig7 Prevalence of epilepsy in industrialized countries

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Fig 8 Prevalence of epilepsy in developing countries. Although the prevalence rate of epilepsy in developing countries is reported to be twice that in the developed world, this may be related to misdiagnosis and inclusion of symptomatic seizures, single seizures, febrile seizures and inactive epilepsy. Regional causal factors such as cerebral cysticercosis and hot water epilepsy might have influenced the results. Four community based surveys representing north, central and south India, have shown prevalence rates per 1000 population of 2.5 for Kashmir (24), 3.6 for Parsis in Mumbai (25), 4.4 for Bangalore (26) and 4.9 for Kerala. Age-Specific Prevalence

Most studies, particularly those from developing countries, report the highest prevalence in the second and third decades of life, with lower prevalence in the elderly. (Fig. 8). Etiology For all total population studies providing information, the majority of cases, typically between 55% and 89% even in developing countries, have no identified cause. (Fig. 9)

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FIGURE 9. Distribution of etiology of epilepsy cases. CP, cerebral palsy; MR, mental retardation

MEDICALLY REFRACTORY EPILEPSY Epilepsy is defined as a condition characterized by recurrent unprovoked seizures; hence at least 2 unprovoked seizures are required for diagnosis of epilepsy. Patients with uncontrolled seizures or those who develop intolerable side effects that interfere with their quality of life, despite maximally tolerated dose of one or more AEDs are considered to have refractory epilepsy . About 70- 80% of patients in developing countries with epilepsy are rendered Seizure free with AEDs. The remaining are considered to have refractory epilepsy. In general , patients who continue to exhibit 2 or more disabling seizures per month for a period of 2 years or more despite supervised trials( six months each) twice with monotherapies and once with polytherapy are candidates for detailed evaluation in a comprehensive epilepsy program. Data from a Danish registry of unselected patients with partial epilepsy

21 | Page suggest a cumulative incidence for intractable epilepsy of 135 per 100,000.(27)

CANDIDATE SELECTION FOR SURGERY Epilepsy surgery may be considered by anyone whose seizures recur despite use of appropriate antiepileptic drugs (AEDs). For properly selected patients,surgery offers a relatively safe and effective means of either abolishing seizures, diminishing their severity, or reducing seizure frequency. Because most of the benefits conferred by surgery accrue when seizures are completely stopped, palliative surgery is a viable option only if it would improve quality of life or lessen the risk of injury or death. The most common types of seizures that lead people to consider surgery are those that cause alteration of consciousness or awareness or injury. These seizures have the greatest potential to cause injury and impair quality of life. They are common indications for surgery because of their adverse psychosocial and medical repercussions. Loss of awareness prevents legal operation of a motor vehicle, reduces employment opportunities, diminishes educational choices, and imposes psychological burdens.

Medical Intractability

Certain risk factors dictate a low probability of seizure remission. The likelihood of persistent seizures is increased by additional factors such that patients with multiple risk factors have the poorest outcome.(27)

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High seizure frequency in the form of daily or weekly episodes constitutes a major risk factor for medical intractability, whereas seizure clustering increases the risk still further.(28) Early seizure onset, particularly in infancy, predicts seizure persistence,(29) and infantile hemiconvulsive status epilepticus (SE) is specifically linked to the development of TLE.(30) Motor convulsions in a nonconvulsive disorder are a risk factor independent of the number of lifetime episodes.(31) Patients with organic brain damage are less likely to undergo spontaneous seizure remission.(28) Thus, abnormal neurologic status by physical examination or neuroimaging criteria is associated with both a greater risk of developing epilepsy and a reduced likelihood of remission. As a rule, the more severe the brain damage, the greater the likelihood of seizure persistence.(32) Identification of a Surgically Remediable Syndrome

A significant proportion of epilepsy surgery candidates manifest seizures in the context of specific epilepsy syndromes. Candidates for excisional procedures usually have localization-related epilepsy syndromes, whereas candidates for commisural surgery typically have generalized epilepsy syndromes. Patients with surgically amenable epilepsy syndromes fall within the cryptogenic and symptomatic etiologic groups, because idiopathic epilepsy syndromes are genetically determined and are therefore unlikely to be influenced by surgical intervention. Many epilepsy syndromes are well characterized and have defined prognoses, simplifying the selection process; thus, idiopathic partial and generalized epilepsies are not surgically amenable, whereas surgery might be considered the treatment of choice for some specific epilepsy syndromes 23 | Page such as mesial TLE; neocortical epilepsy caused by discrete, easily resectable lesions; chronic epilepsy associated with Sturge-Weber syndrome; tuberous sclerosis; focal cortical dysplasia; hemimegalencephaly; and Rasmussen syndrome.

GOALS OF SURGERY

Two broad surgical intervention Curative surgery eradicates seizures and the need for medication, whereas palliative categories of surgical therapy for epilepsy, curative and palliative, define the relative success of surgery lessens seizure severity or frequency or prevents the occurrence of some seizure types. Curative surgery should eliminate the psychosocial disability associated with seizures and therefore remains the best hope for achieving a “normal” life, including improved schooling, greater personal independence, enhanced employment opportunities and attainment of a driver's license. Studies have shown that return to a normal lifestyle after surgery rarely occurs in patients who do not achieve seizure freedom. In some patients, only one of several seizure types is cured by surgery, but this may be a worthwhile outcome. For example, patients with mixed seizure disorders usually benefit from elimination or marked reduction in the frequency of tonic or atonic seizures, due to the reduction in medical risk and attendant injuries (e.g., fractures, lacerations). Similarly, patients with TLE may benefit from abolition of complex partial seizures and tolerate occasionalauras without loss of consciousness. Palliation requires a clear a priori definition of the surgical objectives, so that an intelligent appraisal of results can follow surgery.

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TYPES OF SURGICAL TREATMENTS

Various surgical procedures are available in the armamentarium for temporal lobe epilepsy, lesional neocortical epilepsy, non lesional neocortical epilepsy and hemispheric epilepsy syndromes with good results and resulting in cure in many of the cases. However , it is the secondary generalized epilepsies that are not amenable to focal resections and form an important subset of medically intractable seizures.The symptomatic/cryptogenic generalized epilepsies, such as the Lennox-Gastaut syndrome, bilateral cerebral dysfunction, and bilateral seizure onset, usually preclude focal cortical resection. Atonic, tonic, and tonic–clonic seizures may, in some patients, respond to corpus callosotomy, the rationale being interruption of the rapid secondary bilateral synchrony that underlies these seizures types.(33,34) The indications for corpus callosotomy are not standardized, but patients with “drop attacks” usually respond best. Recurrent episodes of convulsive SE are also eliminated in most cases.(35) The influence of intelligence, EEG abnormalities, and MRI abnormalities on outcome is variable.

CONTRAINDICATIONS FOR SURGERY Absolute Primary generalized epilepsy Minor seizures that do not impair quality of life Relative Progressive medical or neurological disorder.

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Active psychosis, not related to peri-ictal period Behavioural problems that impair rehabilitation IQ <70( for local resective surgery ) Poor memory function in hemisphere contralateral to epipletic focus.

CORPUS CALLOSOTOMY

A number of newer procedures—most notably, multiple subpial transection,vagal nerve stimulation, and deep brain stimulation—have become available in the treatment of seizure disorders, and these have legitimate roles either as alternatives to resective procedures or as strategies when a respective procedure is not an option. (36-40)

Surgical division of the corpus callosum for the treatment of certain medically intractable seizure disorders, at one time about the only alternative to resective surgery.It was first undertaken >60 years ago on the basis of two lines of evidence: (1) The observation of Van Wagenen that epileptic patients who subsequently suffered strokes or tumors involving the corpus callosum often had concurrent improvement in their seizure disorders.(41) (2) A growing experimental literature demonstrating, most notably in the work of Erickson in monkeys, (42) that the corpus callosum was the major route of seizure propagation from epileptogenic focus to generalization. (42-46)

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Van Wagenen went on to perform callosal section in a small number of patients with some success,(41) and similar clinical experiences were reported by Bogen and coworkers (47-49) and Luessenhop.(50-51) It was not until the series of Wilson and coworkers (52) that a sustained clinical experience developed, and over the last three decades, there has been widespread adoption of the surgical procedure. Removing an epileptogenic region with the goal of surgical cure has always been preferred, but in those patients with generalized seizures in whom a discrete epileptogenic region could not be identified or resected, surgical disruption of secondary generalization was logical. Consequently, the earliest patients for this surgery were those who were not candidates for respective surgery but who demonstrated secondary generalization. It was quickly appreciated that of the types of seizures most likely to be helped—drop attacks (variously classified as atonic and akinetic seizures)— are among the most responsive, often being eliminated altogether; tonic and tonic–clonic generalized seizures also have been shown in multiple series to be similarly affected.(53-124) Whereas corpus callosotomy had been performed in fewer patients than had most other epilepsy operations, and in many respects the procedure was not as well understood as other surgeries, it was reasonable that many patients underwent callosal section largely on the basis of their seizure semiology. From a historical perspective, the role of pathology, as well as that of electrophysiologic studies, has been secondary. A spectrum of disease has been encompassed in clinical series. Williamson (120) looked at surgical outcomes in terms of clinical diagnoses and classified patients into groups of

27 | Page infantile hemiplegia, forme-fruste infantile hemiplegia, Rasmussen syndrome,Lennox-Gastaut syndrome, frontal lobe epilepsy, and other secondarily generalized epileptics. Although better outcomes were found in the first two groups, but there was sufficient improvement in all categories to justify surgical intervention. The electrophysiologic role has been an indirect one, by demonstrating the absence of a resectable epileptic region. In addition, however, electroencephalogram (EEG) findings in patients selected for callosotomy have been analyzed by a number of investigators. (125-131) Correlating EEG with surgical results, Geoffroy et al., (67) Spencer et al., (117) and Matsuzaka et al.(132) all reported better results in patients with lateralized EEG abnormalities.The majority of patients have evidence of bilaterally synchronous epileptiform activity, and this does not necessarily represent a bad prognostic sign. The significance of bilateral, independent foci is undetermined.

The impact of neuroimaging on the callosotomy experience has bee limited.Lateralized structural lesions have been believed to be associated with a better surgical outcome, (117,133) but in the selection process their presence or absence has always been secondary to clinical and electrophysiologic information. As imaging technologies continue to evolve with increasing sensitivity and specificity, they are directing such aspects of the seizure evaluation as intracranial recording electrode placement. This increased sophistication of seizure investigation affects both patient selection and perhaps the surgery itself. From the isolated clinical experiences of Van Wagenen, (41) Bogen and

28 | Page coworkers, (47-49) Luessenhop, (50-51) and Wilson and coworkers, (52) callosum section has seen a cautious but marked increase in application over the last several decades. Less than a dozen centers were performing callosal section 1982 when the first Dartmouth workshop on the corpus callosum was held; nearly every surgical epilepsy center performs this surgery today.

ANATOMY OF THE COMMISURES OF BRAIN Corpus Callosum Commissural fibres cross the midline, many linking corresponding areas in the two cerebral hemispheres. By far the largest commissure is the corpus callosum. Others include the anterior, posterior and habenular commisures, and the commissure of the fornix. The corpus callosum is the largest fibre pathway of the brain. It links the cerebral cortex of the two cerebral hemispheres, and it roofs much of the lateral ventricles. It forms an arch 10 cm in length, with an anterior end 4 cm from the frontal poles and a posterior end 6 cm from the occipital poles.

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FIG:10 Commisural and association fibre tracts

Its anterior portion is known as the genu. This recurves posteroinferiorly in front of the septum pellucidum, then diminishes rapidly in thickness and is prolonged to the upper end of the lamina terminalis as the rostrum. The trunk of the corpus callosum arches back and is convex above. It ends posteriorly in the expanded splenium, which is its thickest part. The median region of the trunk of the corpus callosum forms the floor of the great longitudinal fissure. Here, it lies close to the anterior cerebral vessels and the lower border of the falx cerebri, which may contact it behind. On each side, the trunk is overlapped by the cingulate gyrus, separated from it by the callosal sulcus. The inferiorsurface of the corpus callosum is concave in its long axis. The septum pellucidum is attached to it anteriorly. Posteriorly, it is fused with the fornix and its commissure.

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The superior surface of the callosal trunk is covered by a thin layer of grey matter, the indusium griseum. This extends anteriorly around the genu then, on the inferior aspect of the rostrum, continues into the paraterminal gyrus. It contains narrow longitudinal bundles of fibres on each side, the medial and lateral longitudinal striae. Posteriorly, the indusium griseum is continuous with the dentate gyrus and hippocampus through the gyrus fasciolaris . The splenium of the corpus callosum overhangs the posterior ends of the thalami, the pineal gland and tectum, but is separated from them by several structures. On each side the crus of the fornix and gyrus fasciolaris curve up to the splenium. The crus continues forwards on the inferior surface of the callosal trunk, but the gyrus fasciolaris skirts above the splenium, then rapidly diminishes into the indusium griseum. The tela choroidea of the third ventricle advances below the splenium through the transverse fissure, and the internal cerebral veins emerge between its two layers to form the great cerebral vein. Posteriorly the splenium is near the tentorium cerebelli, great cerebral vein and the start of the straight sinus. Nerve fibres of the corpus callosum radiate into the white matter core of each hemisphere, thereafter dispersing to the cerebral cortex. Commissural fibres forming the rostrum extend laterally, below the anterior horn of the lateral ventricle, connecting the orbital surfaces of the frontal lobes. Fibres in the genu curve forwards, as the forceps minor, to connect the lateral and medial surfaces of the frontal lobes. Fibres of the trunk pass laterally, intersecting with the projection fibres of the corona radiata to connect wide neocortical areas of the hemispheres Fibres of the trunk and splenium, which form the roof and lateral wall of the posterior horn and the lateral wall of the

31 | Page inferior horn of the lateral ventricle, constitute the tapetum. The remaining fibres of the splenium curve back into the occipital lobes as the forceps major.

Fig:12 Transverse section through Corpus callosum

Interhemispheric connections through the corpus callosum do not all represent a simple linking of loci in one hemisphere with the same loci in the other. In areas containing a clear representation of a contralateral sensorium (e.g. body surface, visual field), only those areas that are functionally related to midline representation are linked to the contralateral hemisphere. This is most clearly seen for the visual areas, where the cortex containing the representation of each midline retinal zone is linked to its counterpart on the contralateral side. A similar arrangement is seen in somatic areas, where the trunk

32 | Page representation is callosally linked, but the peripheral limb areas (hand and foot) are not. Connections that link the same, or similar, areas on each side are termed homotopic connections. The corpus callosum also interconnects heterogeneous cortical areas on the two sides (heterotopic connections). These may serve to connect functionally similar, but anatomically different, loci in the two hemispheres, and/or to connect functional areas in one hemisphere with regions that are specialized for a unilaterally confined function in the other.

Anterior commissure The anterior commissure is a compact bundle of myelinated nerve fibres, which crosses anterior to the columns of the fornix and is embedded in the lamina terminalis, where it is part of the anterior wall of the third ventricle. In sagittal section it is oval, its long (vertical) diameter is 1.5 mm. Laterally it splits into two bundles. The smaller anterior bundle curves forwards on each side to the anterior perforated substance and olfactory tract. The posterior bundle curves posterolaterally on each side in a deep groove on the anteroinferior aspect of the lentiform complex, and subsequently fans out into the anterior part of the temporal lobe, including the parahippocampal gyrus. Areas thought to be connected via commissural fibres include: the olfactory bulb and anterior olfactory nucleus; the anterior perforated substance, olfactory tubercle and diagonal band of Broca; the prepiriform cortex; the entorhinal area and adjacent parts of the parahippocampal gyrus;

33 | Page part of the amygdaloid complex (especially the nucleus of the lateral olfactory stria); the bed nucleus of the stria terminalis and the nucleus accumbens; the anterior regions of the middle and inferior temporal gyri.

INDICATIONS FOR CORPUS CALLOSOTOMY

The principal candidates for callosal section are those medically intractable epileptic patients in whom a resectable seizure focus cannot be identified and whose generalized seizures are believed likely to be ameliorated by disruption of seizure propagation. Patients in whom seizure semiology, electrophysiologic studies, neuroimaging, and neuropsychologic testing have shown localized disease amenable to resection are excluded. The remaining candidate pool is heterogeneous, including patients with infantile hemiplegia, forme-fruste infantile hemiplegia, Rasmussen syndrome, Lennox-Gastaut syndrome, frontal lobe epilepsy, and other secondarily generalized epilepsies. Selection criteria in addition to the principal exclusion of resectable disease,include (a) Medical intractability of at least 2 and 2 years' duration, with exhaustive anticonvulsant regimens and documented adequate serum anticonvulsant levels. (b) Generalized seizures, usually major motor or akinetic in type.

(c) Potential functional benefit if improvement in the seizure disorder is achieved.

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In the studies which were reviewed, the patients were not excluded patients from surgery because of retardation, age, mixed hemisphere dominance, (82,106) lack of demonstrable partial seizure onset, or bilaterally independent EEG abnormalities, although the likelihood of success may be less in certain instances. The goal of surgery with callosal section is distinguished from that of other epilepsy surgeries in usually being palliation rather than cure. Although a seizure-free patient is always hoped for, such an outcome is achieved in only 5% to 10% of patients. (135-136) Callosal section achieves a significant reduction and perhaps elimination of certain seizure types, such as drop attacks or secondarily generalized seizures, but often with persistence of attenuated partial seizure activity. The positive impact of such an outcome on these patients is often dramatic and greatly appreciated.

STANDARD OPERATIVE PROCEDURE

Patient is positioned supine with head on MFK clamp , in neutral position of rotation and given a slight elevation of about 30 degrees. A right pericoronal parasagittal laterally based inverted U shaped scalp flap is fashioned .A pericoronal parasagittal four burr hole craniotomy is performed across the superior sagittal sinus (SSS) and dura is opened based on SSS. Intradural word is performed on operating microscope .The interhemispheric adhesions if present are lysed and the transversely running fibres of the corpus callosum are visualized in the depths. Leyla retractors are applied on either side to maintain the visualization. Callosal sectioning is started over the body of CC and about 1 cm of transverse extent id 35 | Page suctioned out. Sectioning is carried out further into the genu and rostrum and anterior commisure is visualized and sectioned. Posteriorly, the sectioning is carried into splenium till the vein of Galen in visualized in the quadrigeminal cistern. Visualization of both the fornices is maintained throughout and the forniceal commisure is also sectioned. Haemostasis is secured and dura is closed primarily. Closure follows standard surgical practice. The patient is observed in the neurosurgical observation unit overnight and transferred to the epilepsy ward the following morning.

COMPLICATIONS OF CORPUS CALLOSOTOMY

In addition to the surgical complications encountered during the procedure, the most notable complication of corpus callosotomy is the disconnection syndrome. The interhemispheric disconnection does not interfere with most activities of daily living but becomes apparent in the failure, by a left hemisphere dominant individual, to perform tasks such as the following:

• Naming an object briefly presented to the left hemifield, although the same can be chosen by the left hand from an array of different objects.Lack of visual transfer may also be evident at the bedside by testing the visual fields with the usual confrontation method, which reveals a double hemianopia. Reading words briefly presented to the left hemifield only (left hemialexia).

• Imitating with one hand the position of the contralateral hand, which is kept hidden from view.

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• Naming objects, kept from view, palpated by the left hand (unilateral tactile anomia).

• Apraxia of the left body may be evident. The left hand may make more errors in matching-to-sample tasks when it is not possible to see the stimulus that is to be matched. A callosal lesion caused left unilateral ideomotor apraxia but without left-sided agraphia, suggesting that the callosal fibers for writing cross more posteriorly than those for praxis, which seem to cross in the more rostral part of the posterior half of the callosum.

• Copying a somewhat complex design with the right hand, which is clearly outdone in the same task by the performance of the left hand (right-hand constructional apraxia).

Lack of intermanual coordination and even a situation in which the left hand acts independently from the patient's volition (alien hand sign) may result from combined callosal and mesial frontal damage, and seems to correlate with damage of the midportion of the corpus callosum.

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AIMS

1. To review the indications and seizure types encountered in the patients undergoing corpus callosotomy at our centre. 2. To evaluate the seizure out of these patients. 3. To evaluate the impact of corpus callosotomy on the emotional state and educational achievements of the patients. 4. To evaluate the impact of the procedure on the care givers and family members of the patient.

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MATERIALS AND METHODS

The study is a retrospective analysis of the consecutive patients undergoing corpus callosotomy (CC) for intractable seizures from 1994 to Sep 2010. Patient data was obtained from case sheets, regular clinical follow

39 | Page up under epilepsy program, postal communication, telephonic conversation and personal interviews with relatives. Patient data was recorded in a structured Proforma designed for the study (Apendix 1). Patients underwent presurgical evaluation with following objectives:

9 Establish the diagnosis of epileptic seizure 9 Define the electro-clinical syndrome 9 Delineate the lesion responsible for seizure 9 Evaluate the past AED treatments and make sure that adequate medical treatment has been provided 9 Select ideal surgical candidates with electro-clinico- radiologic correlation 9 Ensure that the surgery will not result in disabling neuro- psychological deficits

PRESURGICAL EVALUATION

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9 Review the history , past AED treatments, seizure frequency and EEG 9 Medical and Neurological Examination 9 16 channel EEG recording, awake and sleep 9 Neuropsychological evaluation 9 Psycho-Social evaluation 9 Visual field charting 9 MRI with protocol for hippocampal volume loss and sclerosis 9 Ictal VEEG recording (upto 5 days) 9 Intracarotid amobarbital testing for language and memory distribution.

SURGICAL PROCEDURE

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Patient is positioned supine with head on MFK clamp , in neutral position of rotation and given a slight elevation of about 30 degrees. A right pericoronal parasagittal laterally based inverted U shaped scalp flap is fashioned .

Fig 13: Positioning and Scalp flap for corpus callosotomy

A pericoronal parasagittal craniotomy is performed across the superior sagittal sinus (SSS) and dura is opened based on SSS.

Fig 14: Craniotomy for Corpus callosotomy

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Intradural word is performed on operating microscope .The interhemispheric adhesions if present are lysed and the transversely running fibres of the corpus callosum are visualized in the depths.

Fig 15: Interhemispheric dissection

Leyla retractors are applied on either side to maintain the visualization. Callosal sectioning is started over the body of CC and about 1 cm of transverse extent id suctioned out. Sectioning is carried out further into the genu and rostrum and anterior commisure is visualized and sectioned. Posteriorly, the sectioning is carried into splenium till the vein of Galen in visualized in the quadrigeminal cistern. Visualization of both the fornices is maintained throughout and the forniceal commisure is also sectioned. Haemostasis is secured and dura is closed primarily. Closure follows standard surgical practice. The patient is observed in the neurosurgical observation unit overnight and transferred to the epilepsy ward the following morning.

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FOLLOW UP

The AEDs are left unaltered till the first follow up at 1 and a half months. The following protocol is used to follow up the patients postoperatively:

At 7-10 days EEG Visual field charting Neuropsychological evaluation Seizure count At 3 months EEG Visual field charting Neuropsychological evaluation Psychiatric evaluation Seizure count At One Year EEG Visual field charting Neuropsychological evaluation Psychiatric evaluation Seizure count Educational/employment status Quality of life assessment Yearly Comprehensive outcome assessment Quality of life assessment

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Comprehensive outcome assessment Psychological Score A battery of neuropsychiatric tests carried out pretreatment is repeated SCORE Improvement adequate to affect ADL 1 Improved but inadequate to change ADL 2 No change 3 Worse 4

Psychiatric Score Assessed by interviews with patient and relatives, pre and postoperatively SCORE Improved 1 Same 2 Worsening of preoperative psychiatric symptoms 3 Development of new symptoms 4

Educational Score Assessed by interviews with relatives SCORE Improved 1 Same 2 Worse 3

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Employment Score SCORE Pretreatment unemployed post treatment 1 employed or in vocational training No change 2 Pretreatment unemployed post treatment 3 under employed or unemployed

Seizure Score Score Seizure free, off AED 0 Seizure free, need for AED uncertain 1 Seizure free , need AED 2 Auras only 3 Non disabling seizures only 4 1-3 /yr 5 4-11/yr 6 1-3/month 7 1-6/week 8 1-3/day 9 4-10/day 10 >10/day 11 Status epilepticus without barbiturate coma 12

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RESULTS AND ANALYSIS

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I. DEMOGRAPHIC DATA A total of 20 patients who underwent CC were included in the study. 1.Gender:

Eighteen patients were males and two were females .

Sex distribution

Male Females

10%

90%

Fig 16: Seizure distribution across the sexes

2. Age:

Range of 2 -35 yrs and median age of 8Yrs.

48 | P age

14

12

10

8

6

4

2

0 <10 10.1 -20 20-30 30-40

Fig 17: Seizure distribution in various age groups(X axis:Age range : Y Axis: n(patients)) Nineteen patients had moderate to severe mental retardation and 16 had spasticity of limbs to some degree.

3. Seizure Profile:

Six seizure types were recognized of which GTCS, atonic, tonic and myoclonic seizures occurred with almost equal frequency.

14

12

10

8

6

4

2

0 GTCS Focal CPS Tonic Atonic Myoclonic

Fig 18: Frequency of various seizures encountered X axis:Type of seizure ; Y axis:Number of patient

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Median age of onset of seizures was 1.5 Yrs and mean interval between seizure onset to surgery was 12.3 Yrs. Seventeen patients underwent complete callosotomy and three were incomplete.

II. SEIZURE OUTCOME 1.Drop attacks (atonic seizures) Among the various seizure types, drop attacks were the most responsive to the callosotomy. Satisfactory out-come was achieved in 12 (92%) of 13 patients .Five patients collapsed after partial seizures after the surgery, but none incurred physiological injuries. The frequency of preoperative drop attacks was daily in all 13 patients . After surgery, the frequency of residual drop attacks was weekly in 1 patients and occasionally(less than 1 per month) in 2.

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30%

25%

20%

15%

10%

5%

0% Atonic 3 months Atonic 6 months Atonic 12 Atonic 24 months months

Fig 19: Time trend of response of atonic seizures to corpus callosotomy X axis:Time of follow up Y axis: Percentage residual seizures compared to preop

2. Generalized seizures

Of the patients with generalized seizures, half achieved at least 50% reduction in seizure frequency (GTSs, 53%; GTCSs, 63%; atypical absence, 53%), and one third achieved satisfactory seizure reduction (GTSs, 32%; GTCSs, 31%; atypical absence, 23%) . Among 52 patients with disabling generalized sei-zures, including drop attacks, GTSs, and GTCSs, satisfactory outcome was achieved in 32 (62%) patients.

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80%

70%

60%

50%

40%

30%

20%

10%

0% GTCS 3 months GTCS 6 months GTCS 12 GTCS 24 months months

Fig 20: Time trend of response of GTCS to corpus callosotomy X axis:Time of follow up Y axis: Percentage residual seizures compared to preop

70%

60%

50%

40%

30%

20%

10%

0% Tonic 3 months Tonic 6 months Tonic 12 months Tonic 24 months

Fig 21: Time trend of response of tonic seizures to corpus callosotomy X axis:Time of follow up Y axis: Percentage residual seizures compared to preop

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50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% Myoclonic 3 Myoclonic 6 Myoclonic 12 Myoclonic 24 months months months months

Fig 22: Time trend of response of myocloic seizures X axis:Time of follow up Y axis: Percentage residual seizures compared to preop 3.Partial seizures

Among the patients with partial seizures, at least 50% seizure reduction was achieved in 58% of the patients with simple partial seizures and 20% of the patients with complex partial seizures .New types of seizures, mostly simple partial seizures, emerged in 12 patients after the intervention, but these did not interfere with daily life.

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60%

50%

40%

30%

20%

10%

0% CPS 3 months CPS 6months CPS 12 months CPS 24 months

Fig 23: Time trend of response of CPS to procedure X axis:Time of follow up Y axis: Percentage residual seizures compared to preop

III. ASSESSMENT OF EMOTIONAL STATE With the passage of time most of these severely hyperactive patients became more emotionally stable as is evident from the changing distribution of number of patients in each of the proposed categories assessing the emotional status.

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12

10

8

6

4

2

0

Fig 24: Distribution of cases across various emotional states preoperatively and at various points of time at follow up. X axis: Stable A, Mildly hyperactive B, Severely hyperactive C, Apathetic D Y axis : Number of patients

IV. LEVEL OF DEMAND ON CAREGIVERS

In parallel with more stable emotional state and decreased frequency of seizures, the requirement of caretakers to be constantly around the patients came down drastically .

55 | P age

14 12 10 8 6 4 2 0

Fig 25: Distribution of demand on bystanders for care preopoperatively and at various points of time at follow up X axis: level of care required A:Requires 1 or more bystanders throughout B:Requires 1 or more bystanders in close quarters most of the time C:Some degree of supervision D:No supervision Y axis: number of patients

V. LEVEL OF SATISFACTION OF CAREGIVERS

Most of the families expressed satisfaction with the outcome of the procedure and there was good correlation between satisfaction and

56 | P age

decreasing seizure severity as well as decreased demand by patients on caretakers .

14

12

10

8

6

4

2

0 ABCD

Fig 26: Distribution of patient caretakers across various levels of satisfaction X axis: level of satisfaction Very good – A Good- B Fair- C Poor – D Y axis: Number of patients

VI. SURGICAL COMPLICATIONS No perioperative deaths occurred and no neurological deficits

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persisted.No patients showed any significant change change in the intellectualquotient (IQ) after corpus callosotomy. No new neurological deficits were notes .The most frequent surgical complications encountered were surgical site complications including subgaleal fluid collection(n=8),partial wound dehiscence (n=1) and superficial wound necrosis(n=1).Three patients experienced a transient akinetic state that persisted for >1 week and dissipated within a few weeks. As most patients were moderate to severely mentally retarded, testing for disconnection syndrome was not feasible.

VII. SURGICAL OUTCOME AND PROGNOSTIC INDICATORS

The analysis revealed younger age to be independently predictive of improvement in overall daily function and family satisfaction. A satisfactory reduction in drop attacks was obtained in 12 of 13 patients with total section.

VIII. RELATIOSHIP AMONG SEIZURE OUTCOME, DAILY FUNCTION AND SATISFACION

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Almost all of the patients with improved daily function were satisfied with corpus callosotomy. However, the patients who did not achieve satisfactory reduction of drop attacks and did not obtain improved daily function were dissatisfied with this surgical procedure.

I

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Discussion

In the present callosotomy series, presurgical factors independently related to seizure outcome were analysed. Statistically valid comparisons between

60 | Page complete and partial callostomies could not be made because great majority of our patients (n=17) underwent total callosotomy. However, all four patients who underwent partial callosotomy constitute the less satisfied group. A satisfactory reduction of drop attacks was obtained in 94%of patients with total section. However, other presurgical factors, including age at surgery, severe mental retardation, and lateralized findings in EEG, MRI, or clinical examination, were not significantly related to satisfactory reduction of drop attacks.

However, in the present study as aginst several others, severe mental retardation (4,5,15,16) and clinical, radiological, or EEG evidence of a unilateral lesion (137-138,142,147-149) was not significantly related to surgical outcome after callosotomy.

In the present analysis, patients with drop attacks as a primary criterion were selected for callosotomy and considered cessation or <90%reduction in drop attacks to be a satisfactory outcome. One reason for these choices was that drop attacks are the most severe seizure type and place a severe burden on both patients and their families. Because 82% of patients had daily or weekly drop at-tacks before the surgery, they still could be expected to face a considerable risk of physiological injury and their families would still have to provide continuous stressful care even if the drop attacks were reduced to <50% in frequency.

Another reason why this study focused on drop attacks was that this seizure type can be easily identified by the patients' families. Although the families received sufficient preoperative education about the purpose of

61 | Page callosotomy and the low likelihood of complete cessation of all seizures (146), they were more or less disappointed by the residual seizures and anxious about the surgical outcome in general. Because drop attacks are identifiable by falls only (144), the success of surgery can be easily assessed by the patient's family.

In addition to seizure outcome of drop attacks, presurgical factors that influence overall daily function as assessed by the parents were also examined. It was found that the younger patients had significantly better outcome in overall daily function, with improvements noted in 77% of patients aged <18 years old. However, overall daily function was impaired in 27% of patients aged at least 18.

The improvements in hyperactivity and emotional well-being found in the present series have already been stressed as additional benefits in callosotomy for children (140-41,145). Claverie et al. (143) statistically demonstrated that younger patients had better outcome in daily life and better psychosocial adjustment. In the previous reports, overall quality of life as assessed by parents was improved in 72% and 81% of children (140,145) but in only 46% of patients aged at least 26 years old (141). In contrast to the benefits in daily function, 27%of adults and 6% of children were assessed as impaired in overall daily function. Finally, presurgical factors that influence satisfaction with callosotomy were examined. It was found that 83% of parents were satisfied with this surgical procedure. This rate is as high as that reported in other series (145- 46). Also, our results showed that parents of younger patients were more satisfied than those of older patients. As for effect of seizure reduction and

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QOL improvement on family satisfaction, the present study indicated that improved daily function was somewhat more important than seizure outcome of drop attacks. The results suggested that the superior postoperative satisfaction in the younger patients may have been due to the significantly better functional outcome observed in the children.

This retrospective study has some limitations and methodological problems. The results are mainly based on the subjective assessment and opinions of the patients' families rather than objective testing. However, it would have been difficult to use full objective neuropsychological scales and self-assessment by the patients because of the intellectual state of callosotomy patients and their considerable behavioral problems (143). It is also difficult to develop questionnaires on daily function that cover both children and adults, and patients with both normal and severe developmental delays. Therefore, in this study, the assessment of overall daily function and satisfaction assessed by the patients' families was taken as relatively reliable measures for evaluating callosotomy patients (146).

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Conclusion

In the present series, corpus callosotomy was found to be an effective palliative procedure across a whole spectrum generalized epilepsies with dramatic reduction in atonic seizures and significant reduction in GTCS ,tonic and myoclonic seizures. Also, it effectively brought down the level of care demanded from caregivers by the patients and most of them were satisfied with the procedure. Surgical morbidity was minimal and mortality was nil attesting to the safety of the procedure in expert hands.

References 1.Enam S.Ather: History of epilepsy surgery; PJNS Vol 2(2) Apr-Jun 2007

64 | Page

2.Radhakrishnan K: Epilepsy surgery in India; Neurology India Jan-Feb 2009:Vol 57 :Issue1

3.Annegers JF, Dubinsky S, Coan SP, et al. The incidence of epilepsy and unprovoked seizures in multiethnic, urban health maintenance organizations Epilepsia.1999;40(4):502-506

4.de Graaf AS. Epidemiological aspects of epilepsy in northern Norway. Epilepsia. 1974;15(3):291-299

5. Granieri E, Rosati G, Tola R, et al. A descriptive study of epilepsy in the district of Copparo, Italy, 1964-1978.Epilepsia. 1983;24(4):502-514.

6. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota:19 35-1984. Epilepsia. 1993;34(3):453-468

7. Jallon P, Smadja D, Cabre P, et al. EPIMART: prospective incidence study of epileptic seizures in newly referred patients in a French Carribean island (Martinique). Epilepsia. 1999;40(8):1103-1109

8. Jallon P, Goumaz M, Haenggeli C, et al. Incidence of first epileptic seizures in the canton of Geneva, Switzerland.Epilepsia.1997;38(5):547-552

9. Tekle-Haimanot R, Forsgren L, Ekstedt J. Incidence of epilepsy in rural central Ethiopia. Epilepsia.1997;38(5):541-546.

10. MacDonald BK, et al. The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain. 2000;123(Pt 4):665-676.

65 | Page

11. Olafsson E, Ludvigsson P, Gudmundsson G, et al. Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: a prospective study. Lancet Neurol. 2005;4(10):627-634

12. Rwiza HT, Kilonzo GP, Haule J, et al. Prevalence and incidence of epilepsy in Ulanga, a rural Tanzanian district: a community-based study. Epilepsia. 1992;33(6):1051–1056

13. Placencia M, Shorvon SD, Paredes V, et al. Epileptic seizures in an Andean region of Ecuador. Incidence and prevalence and regional variation. Brain. 1992;115(Pt 3):771-782

14. Camfield CS, Camfield PR, Gordon K, et al. Incidence of epilepsy in childhood and adolescence: a population-based study in Nova Scotia from 1977 to 1985. Epilepsia. 1996;37(1):19-23.

15. National Collaborative Perinatal Project, Hauser W, Nelson KB. Epidemiology of epilepsy in children. Cleve Clin J Med. 1989;56(Suppl 2):S185-194

16. Loiseau J, Loiseau P, Guyot M, et al. Survey of seizure disorders in the French southwest. I. Incidence of epileptic syndromes. Epilepsia. 1990;31(4):391-396

17. Annegers JF, Hauser WA, Beghi E, et al. The risk of unprovoked seizures after encephalitis and meningitis. Neurology. 1988;38(9):1407-141. 18. Salazar AM, Jabbari B, Vance SC, et al. Epilepsy after penetrating head injury. I. Clinical correlates: a report of the Vietnam Head Injury Study. Neurology. 1985;35(10):1406-1414

66 | Page

19. Amatniek JC, Hauser WA, DelCastillo-Castaneda C, et al. Incidence and predictors of seizures in patients with Alzheimer's disease. Epilepsia. 2006;47(5):867-872.

20. Schaumann BA, Annegers JF, Johnson SB, et al. Family history of seizures in posttraumatic and alcohol-associated seizure disorders. Epilepsia. 1994;35(1):48-52

21. Leppert M, Anderson VE, Quattlebaum T, et al. Benign familial neonatal convulsions linked to genetic markers on chromosome 20. Nature. 1989;337(6208):647-648.

22. Lewis TB, Leach RJ, Ward K, et al. Genetic heterogeneity in benign familial neonatal convulsions: identification of a new locus on chromosome 8q. Am J Hum Genet. 1993;53(3):670-675

23. Durner M, Sander J, Greenberg DA, et al. Localization of idiopathic generalized epilepsy on chromosome 6p in families of juvenile myoclonic epilepsy patients. Neurology. 1991;41(10):1651-1655

24. Koul R, Razdan S,Motta A .Prevalence and pattern of Epilepsy in rural Kashmir, India. Epilepsia 1988;29: 116-22.

25.Bharucha N E, Bharucha E P, Bharucha A E et al .Prevalence of Epilepsy in Parsi community of Bombay.Epilepsia 1988;29;111-5

26.Mani K.sS , Rangan G, Srinivas H V et al.The Yelandue study: community based approach to epilepsy in rural South India- epidemiological aspects. Seizure 1998;7:281-8.

27.Juul-Jensen P, Foldspang A. Natural history of epileptic seizures. Epilepsia.

67 | Page

1986;24:297–312.

28.Aicardi J. Epilepsy in brain-injured children. Dev Med Child Neurol. 1990;32:191– 202

29. Lindsay J, Ounsted C, Richards P. Long-term outcome in children with temporal lobe seizures. IV:Genetic factors, febrile convulsions and remission of seizures. Dev Med Child Neurol. 1980;22:429–439.

30. Gastaut H, Toga M, Roger J, et al. A correlation of clinical, electroencephalographic and anatomical findings in nine autopsied cases of “temporal lobe epilepsy.” Epilepsia. 1959:56–85.

31. Ounsted C, Lindsay J. The long-term outcome of temporal lobe epilepsy in childhood. In: Reynolds EH, Trimble MR, eds. Epilepsy and Psychiatry. Edinburgh: Churchill Livingstine; 1981:185–215.

32. Trevathan E, Yeargin-Allsop M, Murphy C, et al. Epilepsy among children with mental retardation. Ann Neurol. 1988;24:321.

33. Nordgren RE, Reeves AG, Viguera AC, et al. Corpus callosotomy for intractable seizures in the pediatric age group. Arch Neurol. 1991;48:364–372.

34. Spencer SS, Spencer DD, Williamson PD, et al. Corpus callosotomy for epilepsy. I. Seizure effects. Neurology. 1988;38:19–24.

35. Purves SJ, Wada JA, Woodhurst WB, et al. Results of anterior corpus callosum section in 24 patientswith medically intractable seizures. Neurology. 1988:1194–1201.

36. Buchhalter JR, Jarrar RG. Therapeutics in pediatric epilepsy. Part 2: Epilepsy surgery and vagus nerve stimulation. Mayo Clin Proc. 2003;78:371–378.

68 | Page

37. Gates JR, Rosenfeld WE, Maxwell RE, et al. Response of multiple seizure types to corpus callosum section. Epilepsia. 1987;28:28–34.

38. Karceski S. Vagus nerve stimulation and Lennox-Gastaut syndrome: a review of the literature and data from the VNS patient registry. CNS Spectr. 2001;6:766–770.

39. Polkey CE. Alternative surgical procedures to help drug-resistant epilepsy—a review. Epileptic Disord. 2003;5:63–75.

40. Zhao Q, Tian Z, Liu Z, et al. Evaluation of the combination of multiple subpial transection and other techniques for treatment of intractable epilepsy. Chin Med J (English). 2003;116:1004–1007.

41. Van Wagenen WP, Herren RY. Surgical division of the commissural pathways in the corpus callosum: relation to spread of an epileptic attack. Arch Neurol Psychiatr. 1940;44:740–759.

42. Erickson TE. Spread of the epileptic discharge: an experimental study of the afterdischarge induced by electrical stimulation of the cerebral cortex. Arch Neurol Psychiatr. 1940;43:429–452

43. Kopeloff N, Kennard MA, Pacella BL, et al. Section of the corpus callosum in experimental epilepsy in the monkey. Arch Neurol Psychiatr. 1950;63:719–727

44. Kusske JA, Rush JL. Corpus callosum and propagation of afterdischarge to contralateral cortex and thalamus. Neurology. 1978;28:905–912.

45. Marcus EM, Watson CW. Bilateral synchronous spike wave electrographic patterns in the cat. Arch Neurol. 1966;14:601–610.

69 | Page

46. Marcus EM, Watson CW. Symmetrical epileptogenic foci in monkey cerebral cortex: mechanisms of interaction and regional variations in capacity for synchronous discharges. Arch Neurol.1968;19:99–116.

47. Bogen JE, Fisher ED, Vogel PJ. Cerebral commissurotomy: a second case report. JAMA. 1965;194:1328–1329.

48. Bogen JE, Sperry RW, Vogel PJ. Addendum: commissural section and propagation of seizures. In: Jasper HH, Ward Jr AA, Pope A, eds. Basic Mechanisms of the Epilepsies. Boston: Little, Brown; 1969:439.

49. Bogen JE, Vogel PJ. Cerebral commissurotomy in man: preliminary case report. Bull Los Angeles Neurol Soc. 1962;27:169–172.

50. Luessenhop AJ. Interhemispheric commissurotomy (the split brain operation) as an alternative to hemispherectomy for control of intractable seizures. Am Surg. 1970;36:265–268.

51. Luessenhop AJ, de la Cruz TC, Fenichel GM. Surgical disconnection of the cerebral hemispheres for intractable seizures. JAMA. 1970;213:1630–1636.

52. Wilson DH, Reeves AG, Gazzaniga MS. “Central” commissurotomy for intractable generalized epilepsy: series two. Neurology. 1982;32:687–697.

53. Alpman A, Serdaroglu G, Cogulu O, et al. Ring chromosome 20 syndrome with intractable epilepsy. Dev Med Child Neurol. 2005;47:343–346.

54. Amacher AL. Midline commissurotomy for the treatment of some cases of intractable epilepsy. Child's Brain. 1970;2:54–58.

70 | Page

55. Avila JO, Radvany J, Huck FR, et al. Anterior callosotomy as a substitute for hemispherectomy. Acta Neurochir (Vienna). 1980;Suppl 30:137–143.

56. Blume WT. Corpus callosum section for seizure control: rationale and review of experimental and clinical data. Cleve Clin J Med. 1984;51:319–332.

57. Bouvier G, Mercier C, St Hilaire JM, et al. Anterior callosotomy and chronic depth electrode recording in the surgical management of some intractable seizures. Appl Neurophysiol.1983;46:52–56.

58. Cendes F, Ragazzo PC, da Costa V, et al. Corpus callosotomy in treatment of medically resistant epilepsy: preliminary results in a pediatric population. Epilepsia 1993;34:910–917.

59. Chung SS, Lee KH, Chang JW, et al. Surgical management of intractable epilepsy. Stereotact Funct Neurosurg. 1998;70:81–88.

60. Daszkiewicz P, Dabrowski D, Bachanski M. Callosotomy in the treatment of “catastrophic” drug-resistant epilepsy in children. Neurol Neurochir Pol. 1999;33:839– 846.

61. Fandino-Franky J, Torres M, Narino D, et al. Corpus callosotomy in Colombia and some reflections on care and research among the poor in developing countries. Epilepsia. 2000;41(Suppl 4):S22–S27.

62. Fuiks KS, Wyler AR, Hermann BP, et al. Seizure outcome from anterior and complete corpus callosotomy. J Neurosurg. 1991;74:573–578.

63. Garcia-Flores E. Corpus callosum section for patients with intractable epilepsy. Appl Neurophysiol. 1987;50:390–397.

71 | Page

64. Gates JR, Leppik IE, Yap J, et al. Corpus callosotomy: clinical and electroencephalographic effects. Epilepsia. 1984;25:308–316.

65. Gates JR, Maxwell R, Leppik IE, et al. Electroencephalographic and clinical effects of total corpus callosotomy. In: Reeves AG, ed. Epilepsy and the Corpus Callosum. New York: Plenum Press; 1985:315–328.

66. Gates JR, Rosenfeld WE, Maxwell RE, et al. Response of multiple seizure types to corpus callosum section. Epilepsia. 1987;28:28–34.

67. Geoffroy G, Lassonde M, Delisle F, et al. Corpus callosotomy for control of intractable epilepsy in children. Neurology. 1983;33:891–897.

68. Guerreiro MM, Andermann F, Andermann E. Surgical treatment of epilepsy in tuberous sclerosis: strategies and results in 18 patients. Neurology. 1998;51:1263–1269.

69. Harbaugh RE, Wilson DH, Reeves AG, et al. Forebrain commissurotomy for epilepsy: review of 20 consecutive cases. Acta Neurochir (Vienna). 1983;68:263–275.

70. Hodaie M, Musharbash A, Otsubo H, et al. Image-guided, frameless stereotactic sectioning of the corpus callosum in children with intractable epilepsy. Pediatr Neurosurg 2001;34:286–294.

71. Huck FR, Radvany J, Avila JO, et al. Anterior callosotomy in epileptics with multiform seizures and bilateral synchronous spike and wave EEG pattern. Acta Neurochir (Vienna). 1980(Suppl 30):127–135.

72. Kamida T, Baba H, Ono K, et al. Staged total callosotomy for medically intractable seizures. No To Shinkei. 2000;52:1085–1990.

72 | Page

73. Kawai K, Shimizu H, Yagishita A, et al. Clinical outcomes after corpus callosotomy in patients with bihemispheric malformations of cortical development. J Neurosurg 2004;101(1 Suppl):7–15.

74. Kim DS, Yang KH, Kim TG, et al. The surgical effect of callosotomy in the treatment of intractable seizure. Yonsei Med J. 2004;45:233–240.

75. Kwan SY, Wong TT, Chang KP, et al. Seizure outcome after corpus callosotomy: the Taiwan experience. Child's Nerv Syst. 2000;16:87–92.

76. Kwan SY, Wong TT, Chang KP, et al. Postoperative seizure outcome after corpus callosotomy in reflex epilepsy. Zhonghua Yi Xue Za Zhi (Taipei). 2000;63:240–246.

77. Kwan SY, Wong TT, Chang KP, et al. Postcallosotomy seizure outcome in hemiconvulsion-hemiatrophy-epilepsy syndrome. Zhonghua Yi Xue Za Zhi (Taipei). 2000;63:503–511.

78. Landy HJ, Curless RG, Ramsay RE, et al. Corpus callosotomy for seizures associated with band heterotopia. Epilepsia. 1993;34:79–83.

79. Ma X, Liporace J, O'Connor MJ, et al. Neurosurgical treatment of medically intractable status epilepticus. Epilepsy Res. 2001;46:33–38.

80. Maehara T, Shimizu H. Surgical outcome of corpus callosotomy in patients with drop attacks. Epilepsia. 2001;42:67–71.

81. Makari GS, Holmes GL, Murro AM, et al. Corpus callosotomy for the treatment of intractable epilepsy in children. J Epilepsy. 1989;2:1–7.

73 | Page

82. Mamelak AN, Barbaro NM, Walker JA, et al. Corpus callosotomy: a quantitative study of the extent of resection, seizure control, and neuropsychological outcome. J Neurosurg. 1993;79:688–695.

83. Marino Jr R, Radvany J, Huck FR, et al. Selective electroencephalograph-guided microsurgical callosotomy for refractory generalized epilepsy. Surg Neurol. 1990;34:219–228.

84 . Marino Jr R, Ragazzo PC. Selective criteria and results of selective partial callosotomy. In: Reeves AG, ed. Epilepsy and the Corpus Callosum. New York: Plenum Press; 1985:281–301.

85. McInerney J, Siegel AM, Nordgren RE, et al. Long-term seizure outcome following corpus callosotomy in children. Stereotact Funct Neurosurg. 1999;73:79–83.

86. Murro AM, Flanigin HF, Gallagher BB, et al. Corpus callosotomy for the treatment of intractable epilepsy. Epilepsy Rev. 1988;2:44–50.

87. Mutani R, Bergamini L, Fariello R, et al. Bilateral synchrony of epileptic discharge associated with chronic asymmetrical cortical foci. Electroencephalogr Clin Neurophysiol. 1973;34:53–59.

88. Nordgren RE, Reeves AG, Viguera AC, et al. Corpus callosotomy for intractable seizures in the pediatric age group. Arch Neurol. 1991;48:364–372.

89. Oepen G, Schulz-Weiling R, Zimmermann P, et al. Long-term effects of partial callosal lesions: preliminary report. Acta Neurochir (Vienna). 1985;77:22.

90. Oguni H, Andermann F, Gotman J, et al. Effect of anterior callosotomy on bilaterally synchronous spike and wave and other EEG discharges. Epilepsia. 1994;35:505–513.

74 | Page

91. Oguni H, Hayashi K, Usui N, et al. Startle epilepsy with infantile hemiplegia: report of two cases improved by surgery. Epilepsia. 1998;39:93–98.

92. Oguni H, Olivier A, Andermann F, et al. Anterior callosotomy in the treatment of intractable epilepsies: a study of 43 patients with a mean follow-up of 39 months. Ann Neurol.1991;30:357–364.

93.Pinard JM, Delalande O, Chiron C, et al. Callosotomy for epilepsy after West syndrome. Epilepsia. 1999;40:1727–1734.

94. Pinard JM, Delalande O, Plouin P, et al. Callosotomy in West syndrome suggests a cortical origin of hypsarrhythmia. Epilepsia. 1993;34:780–787.

95. Purves SJ, Wada JA, Woodhurst WB, et al. Results of anterior corpus callosum section in 24 patients with medically intractable seizures. Neurology. 1988;38:1194– 1201.

96. Rappaport ZH, Lerman P. Corpus callosotomy in the treatment of secondary generalizing intractable epilepsy. Acta Neurochir (Vienna). 1988;94:10–14.

97. Rayport M, Corrie WS, Ferguson SM. Corpus callosum section for control of clinically and electroencephalographically classified seizures. In: Reeves AG, ed. Epilepsy and the Corpus Callosum. New York: Plenum Press; 1985: 329–337.

98. Rayport M, Ferguson SM, Corrie WS. Outcomes and indications of corpus callosum section for intractable seizure control. Appl Neurophysiol. 1983;46:47–51.

99. Reeves AG, ed. Epilepsy and the Corpus Callosum. New York: Plenum Press; 1985.

75 | Page

100. Reeves AG, O'Leary PM. Total corpus callosotomy for control of medically intractable epilepsy. In: Reeves AG, ed. Epilepsy and the Corpus Callosum. New York: Plenum Press; 1985:269–280.

101. Reutens DC, Bye AM, Hopkins IJ, et al. Corpus callosotomy for intractable epilepsy: seizure outcome and prognostic factors. Epilepsia. 1993;34:904–909.

102. Roberts DW, Rayport M, Maxwell RE, et al. Corpus callosotomy. In: Engel J Jr, ed. Surgical Treatment of the Epilepsies, 2nd ed. New York: Raven Press; 1993:519–526.

103. Roberts DW, Reeves AG. Effect of commissurotomy on complex partial epilepsy in patients without a resectable seizure focus. Appl Neurophysiol. 1987;50:398–400.

104. Roberts DW, Reeves AG, Nordgren RE. The role of posterior callosotomy in patients with suboptimal response to anterior callosotomy. In: Reeves AG, Roberts DW, eds. Epilepsy and the Corpus Callosum, 2nd ed. New York: Plenum Press; 1995:183– 190.

105. Sainte-Hilaire JM, Giard N, Bouvier G, et al. Anterior callosotomy in frontal lobe epilepsies. In: Reeves AG, ed. Epilepsy and the Corpus Callosum. New York: Plenum Press; 1985:303–314.

106. Sass KJ, Spencer DD, Spencer SS, et al. Corpus callosotomy for epilepsy. II. Neurologic and neuropsychological outcome. Neurology. 1988;38:24–28.

107. Shimizu H. Our experience with pediatric epilepsy surgery focusing on corpus callosotomy and hemispherotomy. Epilepsia. 2005;46(Suppl 1):30–31.

108. Shimizu H, Maehara T. Neuronal disconnection for the surgical treatment of pediatric epilepsy. Epilepsia. 2000;41(Suppl 9):28–30.

76 | Page

109. Smith JR, Lee MR, Jenkins PD, et al. A 13-year experience with epilepsy surgery. Stereotact Funct Neurosurg. 1999;73:98–103.

110. Sorenson JM, Wheless JW, Baumgartner JE, et al. Corpus callosotomy for medically intractable seizures. Pediatr Neurosurg. 1997;27:260–267.

111. Spencer DD, Spencer SS. Corpus callosotomy in the treatment of medically intractable secondarily generalized seizures of children. Cleve Clin J Med. 1988;56(Suppl 1):S69–S77.

112. Spencer SS. Corpus callosum section and other disconnection procedures for medically intractable epilepsy. Epilepsia. 1988;29(Suppl 2):S85–S99.

113. Spencer SS, Elquera ED, Williamson PD, et al. Evolution of seizure types after callosotomy. J Epilepsy. 1992;4:149–156.

114. Spencer SS, Gates JR, Reeves AG, et al. Corpus callosum section for uncontrolled epilepsy. In: Engel J, ed. Surgical Treatment of the Epilepsies. New York: Raven Press; 1987:425–444.

115.Spencer SS, Spencer DD, Sass K, et al. Anterior, total, and two-stage corpus callosum section: differential and incremental seizure responses. Epilepsia. 1993;34:561– 567.

116. Spencer SS, Spencer DD, Williamson PD, et al. Effect of corpus callosum section on secondary bilaterally synchronous interictal EEG discharges. Neurology. 1985;35:1689–1694.

117. Spencer SS, Spencer DD, Williamson PD, et al. Corpus callosotomy for epilepsy. I. Seizure effects. Neurology. 1988;38:19–24.

77 | Page

118. Tanaka N, Fujii M, Akimura T, et al. A case of intractable epilepsy presenting epileptic spasm treated with callosotomy in childhood. No Shinkei Geka. 2004;32:161– 165.

119. Vossler DG, Lee JK, Ko TS. Treatment of seizures in subcortical laminar heterotopia with corpus callosotomy and lamotrigine. J Child Neurol. 1999;14:282–288.

120. Williamson, PD. Corpus callosum section for intractable epilepsy: criteria for patient selection. In: Reeves AG, ed. Epilepsy and the Corpus Callosum. New York: Plenum Press;1985:243–257.

121. Wilson DH, Culver C, Waddington M, et al. Disconnection of the cerebral hemispheres: an alternative to hemispherectomy for the control of intractable seizures. Neurology.1975;25:1149–1153.

122. Wilson DH, Reeves AG, Gazzaniga MS, et al. Cerebral commissurotomy for control of intractable seizures. Neurology. 1977;27:708–715.

123. Wilson DH, Reeves A, Gazzaniga M. Division of the corpus callosum for uncontrollable epilepsy. Neurology. 1978;28:649–653.

124. Wilson DH, Reeves A, Gazzaniga M. Corpus callosotomy for control of intractable seizures. In: Wada JA, Penry JK, eds. Advances in Epileptology: The Xth Epilepsy International Symposium .New York: Raven Press; 1980:205–213.

125. Hanson RR, Risinger M, Maxwell R. The ictal EEG as a predictive factor for outcome following corpus callosum section in adults. Epilepsy Res. 2002;49:89–97.

126. Kwan SY, Lin JH, Wong TT, et al. Prognostic value of electrocorticography findings during callosotomy in children with Lennox-Gastaut syndrome. Seizure. 2005;14:470–475.

78 | Page

127. Kwan SY, Wong TT, Chang KP, et al. Seizure outcomes after anterior callosotomy in patients with posterior-dominant and with anterior-dominant epileptiform discharges. Child's Nerv Syst.2001;17:71–75.

128. Liu Z, Li S, Zhao Q. Surgical treatment of frontal lobe epilepsy—40 cases. Zhonghua Yi Xue Za Zhi. 1999;79:115–117.

129. Matsuo A, Ono T, Baba H, et al. Callosal role in generation of epileptiform discharges: quantitative analysis of EEGs recorded in patients undergoing corpus callosotomy. Clin Neurophysiol. 2003;114:2165–171.

130. Ono T, Matsuo A, Baba H, et al. Is a cortical spike discharge “transferred” to the contralateral cortex via the corpus callosum?: an intraoperative observation of electrocorticogram and callosal compound action potentials. Epilepsia. 2002;43:1536– 1542.

131. Quattrini A, Papo I, Cesarano R, et al. EEG patterns after callosotomy. J Neurosurg Sci. 1997;41:85–92.

132. Matsuzaka T, Ono K, Baba H, et al. Quantitative EEG analyses and surgical outcome after corpus callosotomy. Epilepsia. 1999;40:1269–1278.

133. Wilson DH, Reeves AG, Gazzaniga MS. “Central” commissurotomy for intractable generalized epilepsy: series two. Neurology. 1982;32:687–697.

135. Engel Jr J. Outcome with respect to epileptic seizures. In: Engel J Jr, ed. Surgical Treatment of the Epilepsies. New York: Raven Press; 1987:553–571.

79 | Page

136. Engel Jr J, Van Ness PC, Rasmussen TB, et al. Outcome with respect to epileptic seizures. In: Engel Jr J, ed. Surgical Treatment of the Epilepsies, 2nd ed. New York: Raven Press; 1993;609–621.

137. Geoffroy G, Lassonde M, Delisle F, Decarie M. Corpus callosotomy for control of intractable epilepsy in children.Neurology 1983;33:891±7.

138. Oguni H, Olivier A, Andermann F, Comair J. Anterior callosotomy in the treatment of medically intractable epilepsies: A study of 43 patients with a mean follow-up of 39 months.Ann Neurol1991; 30:357±64.

139. Nordgren RE, Reeves AG, Viguera AC, Roberts DW. Corpus cal-losotomy for intractable seizures in the pediatric age group. Arch Neurol1991;48:364±72 . 140. Cendes F, Ragazzo PC, de Costa V, Martins LF. Corpus callos-otomy in treatment of medically resistant epilepsy: Preliminary results in a pediatric population.Epilepsia1993;34:910±7.

141. Carmant L, Holmes GL, Lombroso CT. Outcome following corpus callosotomy.J Epilepsy1998;11:224±8.

142. Reutens DC, Bye AM, Hopkins IJ, et al. Corpus callosotomy for intractable epilepsy: Seizure outcome and prognostic factors.Epilepsia1993;34:904±9.

143. Claverie B, Rougier A. Life comfort and psychosocial adjustment linked to age at the time of anterior callosotomy.J Epilepsy1995; 8:321±31.

144. Pinard JM, Delalande O, Chiron C, et al. Callosotomy for epilepsy after West syndrome .Epilepsia1999;40:1727±34.

80 | Page

145. Yang TF, Wong TT, Kwan SY, Chang KP, Lee YC, Hsu TC. Quality of life and life satisfaction in families after a child has undergone corpus.Epilepsia1996;37:76±80.

146. Gilliam F, Wyllie E, Kotagal P, Geckler C, Rusyniak G. Parental assessment of functional outcome after corpus callosotomy.Epilepsia1996;37:753±7.

147. Wilson DH, Reeves A, Gazzangia M. Division of the corpus callosum for uncontrollable epilepsy.Neurology1978;28:649±53.

148. Purves SJ, Wada JA, Woodhurst WB, et al. Results of anterior corpus callosum section in 24 patients with medically intractable seizures.Neurology1988;38:1194±201.

149. Spencer SS, Spencer DD, Williamson PD, Sass K, Novelly RA, Mattson RH. Corpus callosotomy. I. Seizure effects. Neurology 1988;38:19±24.

APPENDIX 1

PROFORMA FOR COLLECTION OF DATA ON CORPUS CALLOSOTOMY FOR EPILEPSY

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PATIENT NAME:

AGE:

SEX:

INCOME CATEGORY.

HOSPITAL NUMBER:

ADDRESS:

DATE OF ADMISSION:

DATE OF DISCHARGE:

TYPE OF SEIZURE:

DURATION OF SEIZURES:

FREQUENCY (n/ yr)

ANTIEPILEPTICS(AED) TRIED IN PAST:

AEDs BEFORE SURGERY:

TOXIC EFFECTS OF AEDs.

EEG LOCALISATION OF SEIZURE FOCUS: SCALP EEG

VIDEO EEG

IMAGING FINDINGS:

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CT MRI:

ANY OTHER:

PREOPERATIVE DEFICITS: 1. Motor power all 4 limbs. 2. Tone in bilateral lower limb 3. Gait. A. Normal gait. B. Mildly spastic. c. Severely limited. D. No useful gait. 4. Hand function – Right left. 5. Neck control. 6. Language function. A. Communicates freely, can read/ write. B. Communicating freely, cannot read or write. C. Communicates with close relatives. D. Communicates basic needs. E. No effective communication. 7.Emotional status. Stable Mildly hyperactive. Severely hyperactive. Apathy. Demand on Bystander for care A. Requires 1 or more bystanders throughout. B. Requires presence of bystander in close quarters most of the time. C. Some degree of supervision. D. No supervision.

EXTERNAL EXAMINATION: Contractures –

Injuries on the forhead/ head. A. 2-3 injuries. B. Multiple injuries/ Wearing helmet.

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PREOPERATIVE ASSESSMENT BY PSCYCHOLOGIST:

SURGICAL PROCEDURE:(DATE)

EXTENT OF RESECTION OF CORPUS CALLOSUM: Anterior 2/3rd /Complete

ANTERIOR COMMISSURE SECTIONED: Y/N HIPPOCAMPAL COMMISSURE DIVIDED Y/N

EPENDYMA BREACHED : Y/N

INTRAOP EEG FINDINGS:

PERIOD OF ICU STAY: SENSORIUM ON POD2.

SEIZURES IN POSTOP PERIOD: Y/N

TYPE:

DURATION:

REQUIRED REINTUBATION: Y/N

OPERATIVE COMPLICATIONS : Any hypothalamic dysfunction. Y/N

Injury to ACA Y/N

POST OP IMAGING:

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ANY NEW FOCAL NEUROLOGICAL DEFICITS :

ANY OPERATIVE SITE COMPLICATIONS:

POST OP EEG:

POST OP PSYCHOLOGICAL ASSESSMENT:

FIRST FOLLOW UP:

NEUROLOGICAL EXAMIANTION FINDINGS: 1. Motor power all 4 limbs. 2. Tone in bilateral lower limb 3. Gait. A. Normal gait. B. Mildly spastic. c. Severely limited. D. No useful gait. 4. Hand function – Right left. 5. Neck control. 6. Language function. A. Communicates freely, can read/ write. B. Communicating freely, cannot read or write. C. Communicates with close relatives. D. Communicates basic needs. E. No effective communication. 7.Emotional status. Stable Mildly hyperactive. Severely hyperactive. Apathy. Demand on Bystander for care A Requires 1 or more bystanders throughout. B Requires presence of bystander in close quarters most of the time. C Some degree of supervision. D No supervision.

PSHYCHOSOCIAL ASSESSMENT:

SEIZURE FREQUENCY:

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AEDs BEING USED:

SECOND FOLLOW UP: NEUROLOGICAL EXAMINATION: 1. Motor power all 4 limbs. 2. Tone in bilateral lower limb 3. Gait. A. Normal gait. B. Mildly spastic. c. Severely limited. D. No useful gait. 4. Hand function – Right left. 5. Neck control. 6. Language function. A. Communicates freely, can read/ write. B. Communicating freely, cannot read or write. C. Communicates with close relatives. D. Communicates basic needs. E. No effective communication. 7.Emotional status. Stable Mildly hyperactive. Severely hyperactive. Apathy. Demand on Bystander for care E. Requires 1 or more bystanders throughout. F. Requires presence of bystander in close quarters most of the time. G. Some degree of supervision. H. No supervision.

PSHYCHOSOCIAL ASSESSMENT:

SEIZURE FREQUENCY:

AEDs BEING USED:

LAST FOLLOW UP:

APPENDIX 2 POSTAL QUESTIONNAIRE IN ENGLISH

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APPENDIX 3 POSTAL QUESTIONNARE IN MALAYALAM 87 | Page

INDEX

TOPIC PAGE

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INTRODUCTION 6-11

REVIEW OF LITERATURE 10-36

AIMS 37

MATERIAL AND METHODS 38-45

RESULTS 46-57

DISCUSSION 58-61

CONCLUSION 62

REFERENCES 63-79

APPENDICES 1,2,3 80-86

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