Three possible scenarios exist with regard to the relationship between calci \201 c neuroc ysticercosis and epilepsy: ( 1 ) a non-causal relationship, i.e. simple coincidence of two unrelated diseases in the same individual; ( 2 ) a causal relationship; and ( 3 ) dual path ol- ogy. However, calci \201 c neurocysticercosis does not appear to be a risk factor for medically-intractable epilepsy. In a cross-sectional study of the 512 patients with intract able epilepsy, calci \201 c neuro- cysticercosis was found in eight (1.6 % ) patients, but a clear rela- tionship between calci \201 ed cysticercotic lesions and intractable epilep sy was con \201 rmed in only two (0.4 % ) patients ( 100 ). In one small series, perilesio nal gliosis in relation to a calci \201 c neurocyst- icercus lesion was associated with me dically-intractable epilepsy (K. Radhakrishnan, personal communication). Encephalitis For patients with viral encephalitis, the risk of epilepsy is increased 16-fol d and the increased risk persists for at least 15 years after the episode. In the Olmsted C ounty study, the 20-year risk of unpro- voked seizures was 22 % in those with early seizure s and 10 % in those without early seizures ( 72 ). Epilepsy is one of the common consequenc es of herpes simplex encephalitis (HSE) (Fig. 20. 1 A \200\223D). CHAPTER 20 epilepsy due to tbi, cvd, cns infections, and brain tumors 227 A B C D Fig. 20.1 A \200\223D) Serial MRIs in an individual with presumed herpes simplex encephalit is showing (A) bilateral mesial temporal hyperintensities (more on the right side) on a cor onal T2-weighted image during the acute encephalitic illness and follow-up \202 uid atten uated inversion recovery (FLAIR) (B) and T2-weighted (C) images obtained 3 years later demo nstrating right-sided hippocampal atrophy and sclerosis. Following the encephalitic episode , this individual developed medically-refractory complex partial seizures that were demonst rated to be of right anterior temporal origin on EEG telemetry (D). She remains seizure fre e after standard right antero-mesial temporal lobe resection. Courtesy: Epilepsia with perm ission. Seizure type and semiology Epileptic seizures following CNS infections can be both focal-on set and generalized ( 72 , 101 , 102 ). In the Olmsted County study, the risk of focal-onse t seizures after any CNS infection was increased by 12-fold, while that of generalized-onse t seizures was increased by 3-fold ( 72 ). Myoclonic seizures might also occur ( 101 ). The sei- zure semiology includes automotor seizures, complex motor/ hypermotor seizures, diale ptic seizures, tonic seizures and bilateral asymmetric tonic-clonic seizures. In patients w ith MTS in relation to CNS infection, the seizure semiology is similar to mesial tempo- ral lobe epilepsy associated with other antecedents ( 103 ). action and the side-effect and interaction pro \201 les of the drug. Tolerability is as im portant as ef \201 cacy in determining overall effec- tiveness of the AED. Broad-spectrum AEDs with least cognitive side-effects should be the initial choice; such an approach will be very useful in situations where the seizure type or the epilepsy syn- drome is uncertain . Initial treatment should be with monotherapy and treatment with two or three but not more A EDs may be a useful therapeutic option for patients not responding to monotherapy. Patients who do not attain long-term seizure freedom with the \201 rst three treat- ment schedule s are likely to have refractory epilepsy and such patients are potential candidates for epi lepsy surgery ( 104 , 105 ). There are virtually no data on the long-term prognosis of epi- lepsy related to CNS infecti ons. Remission rates following AED therapy are perhaps similar to other symptomatic epileps ies. The remission rate in patients with epilepsy related to bacterial menin- gitis is abou t 50 % ( 101 ). Remission rates for epilepsy associated Medical treatment The choice of antiepileptic drugs (AEDs) for people with epilepsy related to CNS infections depends on the seizure type and epilepsy syndrome and also takes into co nsideration the mechanism of oxford textbook of epilepsy and epileptic seizures 228 the onset of epilepsy, and seizure-onset localized to one temporal lobe ( 103 , 107 \200 \223111 ). Conversely, postoperative seizure outcome is not favorable in those without a de monstrable focal lesion on MRI, having a short latency period to epilepsy, later age ( > 5 years) at the time of CNS infection, history of encephalitis, or a neocorti- cal origin of seizures ( 72 , 107 \200\223111 ). An association of calci \201 c neurocysticercosis with MTS has been reported by several au thors ( 100 , 113 ). When compared to patients with isolated MTS, those with calci \201 c neurocysticercosis and ipsi- lateral MTS have a lower incidence of febrile seizures, older age at initial precipitating injury or \201 rst seizure, older age at onset of complex pa rtial seizures, higher rates of seizure clustering, and extratemporal/bitemporal interictal discharges. Although prelimi- nary, these observations suggest that MTS associated with ca lci \201 c neurocysticercosis might have a different pathophysiological basis than isolate d MTS. The hypothesis needs to be proven with longi- tudinal follow-up studies. The surgica l approach to a patient with MTS and calcific neurocysticercosis is unclear. In one study, patients underwent anteromesial temporal lobectomy, without resection of the cysticercotic lesion and were rendered seizure free ( 113 ). Others, however, have reported better outcom es following anteromesial temporal lobe resections combined with resection of the calci \201 c lesion (K. Radhakrishnan, personal communication). Fig. 20.2 Computed tomography image showing multiple calci \201 cations as well as cystic lesions in a patient with neurocysticercosis. Brain tumors Epilepsy is one of the most characteristic manifestations of brain tumors and it can signi \201 cantly affect the quality of life of patients with brain tumors. Tumoura l epilepsy is considered to be symp- tomatic, localization-related and manifests as focal o r partial sei- zures with or without alteration of consciousness and/or secondary generaliz ation. with calci \201 c neurocysticercosis is about 72 % (95 % CI 53.7 \200\22385.4) at 3 years and 66 % at 5 years (95 % CI 32.4 \200\22388.2) ( 96 ). As with other symptomatic epilepsie s, prior CNS infection reduces the chance of successful AED withdrawal following a period o f remission in people with epilepsy ( 106 ). High seizure relapse rates in patients with ep ilepsy related to calci \201 ed neurocysticercosis have been reported ( 96 ). Epidemiology of tumoural epilepsy The incidence of epilepsy in patients with brain tumors i s about 30 % ( 114 ). This incidence depends largely on the tumor type (see \200\230Tumor type \200\231 section) (Table 20. 2 ). Epilepsy is often the sole pre- senting manifestatio n of low-grade benign tumors. In contrast, high-grade malignant tumors present with a mixtu re of symptoms and signs including focal neurological de \201 cits, raised intracranial pr essure, and seizures. In population-based samples, brain tumors are the cause of about 4 % of all new-onset epilepsies ( 115 , 116 ). From a different perspective, seizures are the p resenting manifesta- tion in about one-third of the cases of brain tumors ( 117 , 118 ). Epilepsy surgery Surgery is a good option in selected patients with medically-refrac- tory epilepsy related to prior CNS infections, especially in those with discrete, resectable les ions. Common surgical substrates in epilepsy related to CNS infections include hippocampal sclerosis, calci \201 c neurocysticercosis and neocortical gliosis ( 72 , 107 \200\223113 ) (K. Radhakrishnan, personal communication). Neurocysticercosis (including calci \201 c neurocysticercosis) by itself is rarely associa ted with medically-refractory epilepsy that might require surgical treatment. However, limi ted experience with surgical excision of cysticercal lesions has identi \201 ed residual p erilesional gliosis as the dominant pathological feature in the small number of cases in wh ich epilepsy associated with a calci \201 c cysticercus was truly refractory to medical tr eatment. Risk strati \201 cation and mechanisms of epileptogenesis Various factors and mechanisms a re known to be involved in the development of seizures in tumoural epilepsy. These include tumor type (Table 20. 2 ) and its location, peritumoural tissue changes, intrinsic epilepto genic properties of certain tumor cells, and alterations in neurotransmitters and amino aci ds. Mesial temporal sclerosis Among various CNS infections, bacterial meningitis and viral ence phalitis and possibly neurocysticercosis constitute antecedent events for the development o f MTS. In patients with MTS in rela- tion to prior CNS infection, factors associated with g ood post- surgical seizure outcome (Engel \200\231s Class 1a \200\2232) include the occurre nce of CNS infection before the age of 4 years, remote his- tory of meningitis (in comparis on to viral encephalitis, for which the surgical prognosis appears less favorable), documen tation of unilateral MTS in the preoperative MRI, longer latent period to Tumor type The overall incidence of seizures in individuals with low-grade gli- omas (inclu ding dysembryoplastic neuroepithelial tumor (DNET), ganglioglioma and low-grade astrocytoma s/oligodendro- gliomas) is 75 \200\223100 % in comparison to an incidence of 40 \200\22360 % in those with glioblastoma multiforme ( 114 , 115 , 118 ). Thus, low- grade, slow-growing tumors appear to be highly epileptogenic CHAPTER 20 epilepsy due to tbi, cvd, cns infections, and brain tumors 229 Table 20.2 Tumor types associated with epilepsy a Neurotransmitters and amino acids An altered expression of neurotransmitter receptors (main ly ino- tropic and metabotropic glutamate receptors) has been noted in brain tumors ( 128 ) . Besides abnormal receptor expression, alter- ations in levels of gamma aminobutyric acid have also been docu- mented. Both mechanisms might be involved in the generation of seizure s and epilepsy ( 129 ). Low-grade tumors Neuronal and glial neoplasms: Dysembryoplastic neuroepithelial tumor Ganglioglioma Glial neoplasms: Pilocytic astrocytoma Low-grade astrocytoma Pleomorphic xanthoastrocytoma Oligodendroglioma Oligoastrocytoma Secondary epileptogenesis and dual pathology Secondary epileptogenesis refers to the develo pment of a new epi- leptogenic lesion that is distinct from the initial or primary epilep- togenic lesion. The occurrence of recurrent, often prolonged seizures before a certain age (usually 5 years but might be later) is thought to be critical to the development of second ary epileptogen- esis ( 130 ). Of the various cortical structures, the hippocampus is most susceptible to be involved during secondary epileptogenesis. Dual pathology is the presence of additional or concomitant poten- tially-epileptogenic lesion/s distinct from the primar y lesion ( 131 , 132 ). The primary lesion can be either neoplastic, dysplastic, vas- cular , or infective and the secondary pathology most often is hip- pocampal sclerosis. Dual path ology is noted in 15 \200\22330 % of surgical series of patients with medically-intractable epilepsy. High-grade tumors Meningioma Glioblastoma multiforme Metastasis Leptomeningeal tumor Primary central nervous system lymphoma a According to the frequency of occurrence of seizures. Treatment Comprehensive management of epilepsy in patients with brain tumors is often negle cted as epileptologists and neurologists are seldom actively involved in the care of such p atients and oncolo- gists devote their time mostly to the treatment of the tumors ( 133 ). Therefore, only limited data regarding medical treatment of tumoural epilepsy is available in published literature. On the other hand, a little more than a handful of series of cases describing results of surgical treatment of epilepsy associated with low-grade gliomas are available (see \200\230Surgical treatment \200\231 section). (Table 20. 2 ) ( 119 , 120 ). The precise reasons for this are unclear. Perhaps, a longer s urvival period in people with low-grade gliomas might be the reason for the greater number of seizures experienced by them ( 117 , 118 ). A greater propensity to seizures might also be on account of the association of developmental tumors with cor- tical dysplasia, as well as the presence of specialized cells within the tumors, which release neurotransmitters ca pable of inducing sei- zures and epilepsy ( 120 \200\223123 ). In addition, the tumor slowl y de- afferents the neighboring cerebral cortex, which in due course of time develops intri nsic epileptogenic properties. Medical treatment Conventional AEDs Carbamazepine, phenytoin, and phenobarbital are effecti ve AEDs for treatment of localization-related, partial epilepsy. However, these are all pot ent inducers of the hepatic P450 enzyme system. Many of the cancer chemotherapeutic agents used in the treat- ment of brain tumors are metabolized by the P450 enzyme system. Hence, t here are concerns that the metabolism of the cancer chemotherapeutic agents might be increa sed as a result of the concurrent administration of enzyme-inducing AEDs, thereby potential ly compromising their ef \201 cacy and reducing the survival of patients with brain tumors ( 134 ). The cancer chemothera- peutic agents most commonly used in treatment of brain tum ors are lomustine (CCNU), temozolomide, vinblastin, and procar- bazine. In addition, methot rexate and carmustine (BCNU) can be delivered directly to the brain tissue through the intr athecal route and via implantable gliadil wafers, respectively. The enzyme- inducing AEDs r educe the area under curve and maximally-toler- ated doses of lomustine. There are no known interactions between enzyme-inducing AEDs and temozolomide or directly adminis- tered meth otrexate and carmustine. The clinical relevance of drug interactions between enzyme-inducin g AEDs and cancer-chemo- therapeutic agents has not been adequately studied. A retrospec- t ive study in patients with glioblastoma multiforme found that median survival in patients w ho received enzyme-inducing AEDs Tumor location Although more commonly observed with intra-axial tumors, sei- zures can also be the manifestation of extra-axial tumors such as meningiomas. Extra-axial tumors manifes t with seizures as a result of compression of adjacent brain tissue ( 124 , 125 ). Supraten torial tumors, particularly those involving the highly-epileptogenic rolandic/perirolandic cortex and the mesial temporal lobes have particular propensity to manifest with seizures a nd epilepsy. Those located in the occipital and parietal lobes, sellar region, and infraten torial compartment are less likely to manifest with seizures ( 124 ). Alterations in peritumoural homeostasis The potentially epileptogenic cerebral cortex is re ndered hyperex- citable as a result of several factors including deranged blood \200\223bra in barrier integrity leading to alterations in peritumoural microenvi- ronment, enzymatic c hanges, and impaired intercellular connec- tions between adjacent glial cells via connexin gap junction proteins ( 126 ). Brain tumors also have a relatively higher metabolic rate th an normal tissue which creates a relatively hypoxic environment with interstitial acidosis ( 127 ). Marked vasogenic oedema and an increase in the concentrations of sodium, calcium, and serum pro- teins are noted in the peritumoural tissue ( 127 ). Hence, several mechanism s are thought to contribute to the development of sei- zures and epilepsy. oxford textbook of epilepsy and epileptic seizures 230 (mostly carbamazepine) was considerably shorter than in those who received sodium valproate ( 135 ). perioperative and late seizures and of gabapentin in the manage- ment of refractory tumoura l epilepsy, but clearly more experience with the newer AEDs is desirable ( 149 , 150 ). Valproate is a broad-spectrum AED with demonstrated ef \201 cacy in tumoural epilepsy. A r etrospective study compared seizure con- trol in brain tumor patients with valproate, carba mazepine, and phenytoin and found better remission rates with valproate ( 136 ). The doses of valproate can be titrated rapidly to achieve therapeu- tic levels. Although, it is known to reduce temozolomide clearance, the clinical signi \201 cance of this interaction is un certain. The drug has been demonstrated to inhibit histone-deacetylase activity both in vit ro and in vivo leading to apoptosis of cancer cells ( 137 , 138 ). This action can be poten tially exploited to improve survival in brain tumors. Valproate is also known to inhibit th e multidrug- resistance gene ( MDR1 ), which is responsible for AED refractori- ness in pat ients with brain tumors ( 139 ). Although, it can cause hepatotoxicity and abnormal coagula tion pro \201 les, the clinical impact of these side effects has been found to be negligib le ( 135 ). Practical issues in the treatment of tumoural epilepsy with AEDs Use of AEDs in the primary prophylaxis of seizures in individuals with brain tumors : a meta-analysis of trials avail able till 2004 found no signi \201 cant bene \201 t of administration of phenobarbital, p henytoin, and valproate in terms of seizure control at 1 week or 6 months in patients with brain tumors who had never experienced seizures ( 151 ). An American Academy of Neurology p ractice parameter recommended that AEDs should not be routinely used in patients with newly -diagnosed brain tumors ( 118 ). The rec- ommendation is based on an independent meta-analy sis of several studies that concluded that although seizures are common in patients with br ain tumors, there is no evidence to suggest that AEDs reduce the seizure risk in those who do not have prior sei- zures. Rather, the routine use of AEDs is frequently associated with side effects, some of which can be potentially life-threatening (e.g. anticonvulsant hyper sensitivity syndrome). Despite this, the prac- tice of administering prophylactic AEDs, par ticularly covering the perioperative period in patients undergoing craniotomy for supratent orial tumors remains unchecked. When used purely for perioperative prophylaxis, the AED sho uld be withdrawn within 7 days of craniotomy. The use of levetiracetam in this situation ap pears to be gaining favor, although robust evidence supporting its use is still lacking. Newer AEDs Among various newer AEDs, levetiracetam, gabapentin, and lacosamide have no know n drug interactions with any of the cancer chemotherapeutic agents and hence are potentiall y useful drugs in the management of tumoural epilepsy and seizures. Experience with the new er AEDs, particularly levetiracetam in tumoural epi- lepsy is restricted to a handful of un controlled trials and very few small, controlled trials. At least six prospective or retros pective trials of levetiracetam demonstrated ef \201 cacy of the drug as add-on treatment in tumoural epilepsy ( 140 \200\223145 ). In one such trial, it was demonstrated that addit ion of levetiracetam led to more than 50 % reduction in seizure frequency in two-thirds of the patients and that about half of these could be eventually converted to levetira- cetam monotherapy ( 141 ). Other trials, albeit small and with many limitations, likewise demonst rated the ef \201 cacy of add-on levetira- cetam in tumoural epilepsy. In these trials, th e side effects of the drug were found to be insigni \201 cant, and were limited to fatigue , dizziness, mood changes, and somnolence ( 143 ). Monotherapy with levetiracetam in the tr eatment of seizures associated with brain tumors has also been evaluated in few small, unco ntrolled and controlled trials. In these trials, the drug has been found to be safe and ef \201 cacious ( 146 , 147 ). The drug has also been compared with phenytoin for use as an a gent to prevent seizures immediately following craniotomy for brain tumors (up to 7 days po stopera- tively) and found to be safe and equally ef \201 cacious ( 148 ). In the perioper ative period, levetiracetam might be preferable over phenytoin as it is suitable for intrav enous administration, equally ef \201 cacious and is not associated with serious side effe cts observed with phenytoin, such as the Stevens \200\223Johnson syndrome and purple glove syndrome. Moreover, psychiatric adverse effects do not appear to be an issue when levetirac etam is given for short periods (<7 days) in craniotomy patients. The advantages of levetir acetam in the long-term management of tumoural epilepsy are its lack of side effects apart from psychiatric disturbances and any known interactions with cancer chemotherapeutic agent s used in the treat- ment of brain tumors. There is perhaps no experience with leveti- race tam use in the primary prophylaxis of seizures in patients with brain tumors. Choice of AED in individuals with brain tumors with seizures : when patients with brain tum ors present with seizures, long-term use of AEDs for prevention of further seizures is reco mmended (Fig. 20. 3 ). Besides the usual issues that dictate the choice of AED, certain con siderations speci \201 c to brain tumors also in \202 uence the selection of AEDs in such situations. One consideration is the range of interactions between AEDs and cancer-chemoth erapeutic agents. Besides the aforementioned interactions between enzyme- inducing AEDs (ph enobarbital, phenytoin, and carbamazepine and also to some extent, oxcarbazepine and topira mate) and can- cer-chemotherapeutic agents, reduction in the serum levels of sev- eral AEDs has been clearly documented largely due to impaired absorption of the latter across the ga strointestinal mucosa that might be damaged by chemotherapeutic agents ( 152 ). Another con sideration is the potential lack of effectiveness of certain AEDs due to expression of mult idrug-resistance proteins, which appears to be high in individuals with brain tumors ( 153 ). Insuf \201 cient concentration of AEDs in the brain might be due to the effect of multi drug-resistance gene MDR1 (ABCB1 , P-glycoprotein) poly- morphisms. Among various AEDs, phe nytoin, phenobarbital, car- bamazepine, and lamotrigine have been shown to be substrates fo r these gene effects ( 147 ). Levetiracetam appears not to be a substrate for these gene ef fects and valproate has been shown to induce apoptosis in tumor cells expressing MDR1 ; hen ce the use of either levetiracetam or valproate might be advantageous from this stand- poin t ( 141 , 153 ). Withdrawal of AEDs in tumoural epilepsy : no guidelines exist regarding when and how to wit hdraw AEDs in patients with tumoural epilepsy who enter a period of remission. In a retrosp ec- tive study of 62 children with brain tumors and epilepsy in whom AEDs were withdrawn, o ne-third had seizure recurrence within 10 months ( 154 ). AED withdrawal might be a conside ration in Other than the preliminary studies with levetiracetam, there is scanty data regarding the u se of the newer AEDs in treatment or prevention of seizures associated with brain tumors. L imited data exists regarding the use of oxcarbazepine in the prevention of CHAPTER 20 epilepsy due to tbi, cvd, cns infections, and brain tumors 231 Brain tumor More than one seizure No seizures No prophylactic antiepileptic drugs Low-grade tumors (higher risk of epilepsy) High-grade tumors (lower risk of epilepsy) Chemotherapy/ radiotherapy/ debulking/ total removal of lesion Choose appropriate antiepileptic drugs Choose appropriate antiepileptic drugs Medically refractory Good response Periodic follow-up: assess seizure frequency and severity, periodic clinical examination an d repeat magnetic resonance imaging Regular follow-up (by careful clinical examination, periodic magnetic resonance imaging) Surgery Fig. 20.3 A pragmatic approach to patients with epilepsy due to brain tumors. Further plan as depicted in Fig. 20.6 it presents in young people (typically <20 years of age) with chronic, medically-refractory epilepsy with complex partial sei- zures. Cranial computed tomography (CT) demonstrates a pseudo- cystic, cortically-based lesion, sometimes with overlying bone changes in the crani al vault. Likewise, MRI demonstrates a cortical lesion with no mass effect or surrounding o edema but might enhance following injection of gadolinium contrast and might rarely be part ially calci \201 ed (Fig. 20. 4 A \200\223C). The histological hall- mark of the tumor is its glioneuronal element comprising of col- umns lined by glial cells with interspersed \202 oating neuronal cells (Fig. 20. 4 D). Its association with cortical dysplasia is now w ell rec- ognized ( 157 ). The pathological diagnosis may sometimes be handicapped by the ab sence of an adequate volume of tissue, as a result of which the typical disarray of the neu ronal and glial ele- ments might be missed. patients who enter a period of remission following complete resec- tion of low-grade brain tumors but in all the other situations it would perhaps be prudent to continue AED treatmen t for pro- longed periods of time. Effects of other forms of treatment on epilepsy : an interesting ques- tion is whether prim ary oncological treatment offers any bene \201 ts in terms of seizure control in patients with brain tumors. The role of surgery in the management of refractory tumoural epilepsy is discussed in the \200\230Surgical treatment \200\231 section. In small controlled and unc ontrolled studies, both cranial irradiation and administra- tion of chemotherapeutic agents , speci \201 cally temozolomide have been shown to improve seizure control to some extent ( 155 , 156 ). This is an area that requires further study. Surgical treatment Over two-thirds of patients with medically refractory tumoural epilepsy experience complete seizure freedom or substantial reduc- tion in seizure frequency followi ng tumor excision ( 157 , 158 ). Brain neoplasms comprise 10 \200\22330 % of the lesions in various surgi- cal series of refractory focal epilepsies ( 157 , 158 ). Two low-grade tumo rs, DNET and ganglioglioma, are noteworthy in context of their association with medically r efractory epilepsy. Thus, although these tumors constitute only a small proportion of prima ry brain neoplasms overall, they are well represented in surgical series of patients with r efractory epilepsy ( 157 , 158 ). Ganglioglioma : this tumor is the most commonly identi \201 ed tumor in many surgical seri es of medically refractory tumoural epilepsy ( 157 , 158 ). It is typically diagnosed in yo ung individuals (<30 years of age) presenting with protracted medically refractory epilepsy with complex partial seizures. Magnetic resonance imag- ing is exquisitely sensitive in de termining the location and charac- teristics of ganglioglioma (Fig. 20. 5 A \200\223C). The temporal lobe is the most frequent location, but the tumor can be found at any site within the neuraxis. Both solid and cystic components can be iden- ti \201 ed and gadolinium enh ancement is noted in two-thirds of the cases on MRI. Calci \201 cation is noted in one-thi rd of cases and sur- rounding cerebral oedema is very rare. Upon histology, the tumor can b e shown to comprise neoplastic astrocytic elements and dys- plastic neuronal cells (Fig. 20 . 5 D). The astrocytic elements are GFAP ( + ) and synaptophysin ( + ). DNET : This tumor accounts for 10 \200\22320 % of brain tumors in surgical series of refrac tory epilepsy from centers undertaking epi- lepsy surgery ( 120 , 157 ). The tumor is corti cally-located, most frequently in the temporal lobe but might also be located in the fronta l lobe in one-third of the cases ( 120 ). Very characteristically, oxford textbook of epilepsy and epileptic seizures 232 Fig. 20.4 Imaging and histopathological data of a 12-year-old boy with complex partial seiz ures since 2 years of age. A) Axial T2-weighted MRI showing a well-de \201 ned lesion occu pying the left frontal lobe in the paracentral lobule (white arrow). B) Axial FLAIR sequenc e shows that the lesion is predominantly hypointense with a hyper intense rim. C) Axial T1- weighted postcontrast sequence did not show any contrast enhancement. D) Photomicrograph sh owing classical \202 oating neurons (black arrow) and oligodendrocyte-like cells (black a rrow heads), characteristic of a dysembryoplastic neuroepithelial tumor. These \202 oatin g neurons are seen in microcystic spaces with mucoid material (haematoxylin and eosin \227 400). The patient is seizure-free 18 months following lesionectomy without any neurologica l de \201 cits. Fig. 20.5 Imaging and histopathological appearance of ganglioglioma in a 22-year-old female with complex partial seizures since 9 years of age. A) MRI axial T2-weighted sequence, B) coronal T1-weighted sequence and (C) Coronal T2 weighted sequence showing a mass lesion (wh ite arrow) in the mesial temporal lobe (amygdala and head of hippocampus). The lesion had s mall cystic areas within it. There was no contrast enhancement. D) Photomicrograph showing an admixture of neoplastic ganglion cells (black arrow) scattered in between astrocytes, ch aracteristic of ganglioglioma. Multiple calci \201 ed spherules are seen (black arrow head ) (haematoxylin and eosin \227 400). veri \201 cation of the lesion prior to planning radiotherapy or chem- otherapy, and to pr eclude the risks of malignant transformation or hemorrhage into the tumor. All patients wit h medically refractory epilepsy and an MRI-identi \201 ed lesion should proceed through st andard presurgical evaluation (Fig. 20. 6 ). The objective of epilepsy surgery is to render the patient seizure-free without producing unacceptable sequelae. The decision for proceed ing to surgery for control of seizures is undertaken by a multidiscipli- nary team comprisi ng of an epileptologist, neurosurgeon, neuro- radiologist, and a neuropsychologist. The var ious surgical approaches include: Surgical excision is the recommended treatment for gangliogli- oma in individuals with medi cally refractory epilepsy. Good sei- zure outcome is the rule (80 % cases being seizure-fre e at 6 months) but the outcome perhaps depends on the extent of resection and duration of e pilepsy. The oncological prognosis is also generally good and plausibly depends on the exte nt of resection. Malignant transformation has been described. Low-grade glial neoplasms : low-grade glioma, pilocytic astrocy- toma, pleomorphic xanthoas trocytoma, and oligodendroglioma are other low-grade neoplasms frequently associated with t umoural epilepsy ( 157 , 159 ). More than two-thirds of the low-grade glial neoplasms assoc iated with medically refractory epilepsy are located in the temporal lobe. In contrast to D NET and ganglioglioma, malignant transformation invariably occurs after a period of time in other low-grade glial tumors. Hence, total excision of these lesions is an important goal of management. Lesionectomy : this refers to the complete removal of the MRI- identi \201 ed lesion. The resection might be anatomically guided by visual impression of the neurosurgeon during oper ation but increasingly so by modern neuronavigation and image-guidance tools. Extended lesionectomy : many of the developmental, low grade glial tumors are associated wi th cortical dysplasia. Excision of the dysplastic cortex perhaps becomes critical for optim al seizure control in such circumstances. Extended lesionectomy involves Presurgical evaluation and surgical strategies Surgical excision of low-grade glial neoplas ms might be under- taken for control of medically refractory epilepsy, for pathological CHAPTER 20 epilepsy due to tbi, cvd, cns infections, and brain tumors 233 Drug-resistant tumoural epilepsy Review seizure semiology, neurological examination, MRI (high resolution, epilepsy protocol ; 1.5Telsa) Long-term video telemetry, neuropsychological and psychiatric evaluation Ictal SPECT, inter ictal PET, fMRI (if required) Discussion in patient management conference Concordant data: NON-ELOQUENT AREA LESION: Selection for surgery based on electrocortiocogr aphy Concordant data: ELOQUENT AREA LESION: Partial lesionectomy and/ or multiple subpial transe ction Inadequate/discordant data If a reasonable hypothesis can be generated Intracranial EEG monitoring; extraoperative cortical stimulation and mapping (if required) Re-discussion in patient management conference Inadequate/discordant information: Excluded from surgical candidacy Concordant data: Selection for surgery Fig. 20.6 Steps in presurgical evaluation of drug-resistant tumoural epilepsy. EEG, electro encephalography; fMRI, functional magnetic resonance imaging; HR, high- resolution; PET, po sitron emission tomography; SPECT, single-photon emission computed tomography. excision of the lesion with an adjoining rim of tissue around the lesion which is apparentl y normal on MRI. It is achieved with the aid of either prior long-term intracranial electro encephalogram monitoring or intraoperative electrocorticography. It remains a matter of con troversy whether lesionectomy alone or lesionec- tomy with excision of the surrounding epil eptogenic zone is supe- rior in terms of seizure outcome. In one series of surgical excisio ns guided by implanted subdural electrodes, it was observed that the epileptogenic zone fre quently extended beyond the con \201 nes of lesion and at many times involved non-contiguo us regions remote from the lesion. However, the postoperative seizure outcome appeared to d epend on the completeness of resection of the lesion rather than the epileptogenic zone ide nti \201 ed by mapping. When complete resection of the lesion was achieved in these patien ts, the extent of resection of the epileptogenic zone did not appear to affect postoperativ e seizure outcome ( 160 ). In certain situations, however, partial lesionectomy with a more complete epileptogenic zone resection might offer better postoperative seizure control. Th erefore, complete resection of the lesion provides the maximal likelihood of complete seizu re control following surgery but clearly, there are instances in which, carefully-planned r esection of the lesion and of the epileptogenic zone might be advantageous. Extended lesion ectomy might be limited at times due to close proximity of the lesion or epileptogenic zone to eloquent cortex, which can be delineated by functional mapping (either, electrical stimulation during or bef ore surgery or prior functional MRI). When eloquent area hinders further resection of the l esion and epileptogenic zone, multiple subpial transection might be under- taken as an anci llary procedure along with lesionectomy. Tackling dual pathology : whenever possible removal of both the lesion and the hippocampus affords superior seizure outcome when compared with resection of either lesion alone or the hip- pocampus alone in patients with demonstrated dual pathology ( 161 ). However, the ult imate decision to include both the lesion and hippocampus should be individualized and depe nds on the electroclinical and imaging data. References 1. Annegers JF , Rocca WA , Hauser WA . Causes of epilepsy: contributions of the Rochester epidemiology project . 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