Prognostic implications of seizure recurrence in the first year after anterior temporal lobectomy

PURPOSE: Seizure recurrence after anterior temporal lobectomy (ATL) incites concerns of whether seizures will eventually be successfully controlled. Our study evaluated the prognostic significance of seizure recurrence in the first year after ATL. METHODS: The postoperative courses of 175 consecutive patients who had undergone ATL and had > or =2 years of follow-up were studied. Recurrence was considered early if the first seizure occurred within 7 days after ATL and late if it occurred >7 days after ATL. Recurrent seizures were considered provoked when precipitating factors were present, such as interruption of antiepileptic drug (AED) intake. Subsequent outcome was determined at terminal follow-up. RESULTS: Percentage of excellent outcome was comparable between patients whose initial recurrent seizures were auras or simple partial seizures and patients without seizure recurrence in the first year (86.7 vs. 93.1%; p > or = 0.05). However, percentage of excellent outcome was less when the initial recurrent seizure was complex partial, either with or without secondary generalization (44.8%; p < or = 0.01). Outcome was not different between early and late seizure recurrence (excellent in 41.7 vs. 55.7%; p > or = 0.05). Nonetheless, patients with either early or late seizure recurrence were less likely to have excellent outcome than were patients with no seizure recurrence in the first year (p < or = 0.001). Percentage of excellent outcome was best when patients were seizure free in the first year (93.1%), intermediate when initial recurrent seizure was provoked (72.0%), and worst when unprovoked (27.8%) (p < or = 0.001). CONCLUSIONS: In the first postoperative year, the type of initial recurrent seizure, whether aura or complex partial and whether provoked or unprovoked, is associated with long-term prognosis in seizure control after ATL. The timing of the initial seizure recurrence is not as important.     

Discontinuation of antiepileptic drugs after successful epilepsy surgery

OBJECTIVE: To evaluate the frequency and risk factors for seizure recurrence subsequent to antiepileptic drug (AED) withdrawal in patients who underwent surgical treatment for intractable partial epilepsy and were rendered seizure-free. METHODS: The outcome of discontinuation of AED medication was studied retrospectively in 210 consecutive patients who were rendered seizure-free after epilepsy surgery performed between 1989 and 1993. RESULTS: Medical therapy was reduced in 96 patients and discontinued in 84 patients. The seizure recurrence rate after complete AED withdrawal was 14% and 36% at 2 and 5 years. In contrast, only 3% and 7% of the 30 patients who did not alter AED treatment after surgery had recurrent seizures in the same time intervals. After AED discontinuation, seizures tended to recur more often in patients with normal preoperative MRI studies compared with those with focal pathology. However, this difference did not reach significance. Intraoperative electrocorticography, extent of surgical resection, postoperative EEG, and seizure-free duration after surgery were not predictive of seizure outcome after AED withdrawal. CONCLUSIONS: AED withdrawal was associated with seizure recurrence in a significant portion of patients rendered seizure-free by epilepsy surgery. Patients with a normal preoperative MRI study showed a tendency for higher seizure recurrence, whereas the duration of seizure-free postoperative AED treatment interval did not significantly influence the seizure recurrence rate. These results will prove useful in counseling patients about discontinuing AED treatment after successful epilepsy surgery.     

How safe is it to withdraw antiepileptic drugs following successful surgery for mesial temporal lobe epilepsy?

Purpose: To investigate the feasibility of antiepileptic drug (AED) withdrawal following anterior temporal lobectomy (ATL) and to identify the predictors of post withdrawal seizure recurrence. Methods: We prospectively studied the seizure outcome of 310 consecutive patients, who were followed for a minimum of 5 years following ATL for medically refractory mesial temporal lobe epilepsy. In seizure‐free patients, we started AED tapering at 3 months in patients on duotherapy/polytherapy and at 1 year after ATL for those on monotherapy. We used Kaplan‐Meier survival curves to estimate the probability of seizure recurrence and complete AED discontinuation, and compared the attributes of recurred and nonrecurred groups of patients by univariate and multivariate logistic regression analyses. Key Findings: Immediately after ATL, 197 patients were on duotherapy and 101 were on monotherapy. We attempted AED withdrawal in 258 patients (83.2%). Sixty‐four patients (24.8%) had seizure recurrence while reducing AEDs. Of 26 patients who had seizure recurrence after complete AED withdrawal, 24 (92.3%) again became seizure‐free after restarting the AEDs. Absence of hippocampal sclerosis on pathologic examination and abnormal postoperative electroencephalogram (EEG) predicted seizure recurrence on multivariate analysis. At the end of follow‐up duration of 8.0 ± 2.0 years, 163 patients (52.6%) were AED free. The cumulative probability of achieving AED‐free status among patients in whom AED withdrawal was attempted, was 44% at fourth year, 65% at sixth year, 71% at eighth year, and 77% at 10th year after ATL. Significance: AED withdrawal can be safely attempted following successful ATL. Seizure recurrences are few and can be managed easily.     

Surgical Treatment for Partial Epilepsy Among Norwegian Adults

Summary: We conducted a retrospective longitudinal self-controlled study of 124 adult patients treated with resective surgery for medically uncontrolled partial epilepsy from 1949 to 1988. Approximately 65% of the patients experienced >95% reduction in seizure frequency, and 75% had worthwhile improvement of at least 75% seizure reduction. Significant reductions were noted in all major seizure types treatable with resective surgery; complex partial (CPS), simple partial (SPS), and secondarily generalized tonic-clonic seizures (GTC) (all p < 0.05). Tissue pathology and region of resection did not provide significant information with respect to seizure outcome. EEG in the first postoperative year was an important predictor of long-term seizure outcome (p = 0.03). One third of the temporal lobe resected patients had neurologic deficits as a consequence of the resection as compared with 14% of patients with frontal resections (p = 0.03). One third of the deficits among the temporal lobe resected patients were considerable, with possible social implications. Half of the patients with preoperative focal spike activity had a normal EEG postoperatively. One fifth of patients maintained their preoperative epileptic focus after the operation, and about one fifth displayed new foci. Approximately one fourth of the patients were free of medication for a median of 16 years postoperatively, and 60% of patients who were seizure-free were still receiving medication. There was no operative mortality, but the late mortality, as expected, was higher than that of the general population. Two male patients (1.6%) committed suicide.     

Absence seizures with evolution into generalized tonic-clonic activity: clinical and EEG features

PURPOSE: To report the clinical and electrographic features of absence seizures evolving into generalized tonic-clonic (GTC) activity in six patients with idiopathic generalized epilepsy. METHODS: All patients were referred for evaluation of refractory seizures and underwent video-EEG monitoring after discontinuation of their antiepileptic drugs (AEDs). We analyzed the video-EEG recordings for seizure semiology as well as ictal and interictal activity. We also reviewed the initial clinical data in all patients. RESULTS: All patients were women, with a mean age of 27 years (range, 14-43 years). The mean age at seizure onset was 12 years (range, 5-15 years). Family history was positive for epilepsy in four patients. All patients had recorded seizures with an onset that was characteristic of generalized absence clinically and electrographically, with evolution into GTC activity. The EEG onset was with generalized 2.5-to 5-Hz spike-and-wave discharges, with evolution into faster rhythmic activity. Interictal EEG recordings showed generalized 2-to 5-Hz spike-and-wave discharges. All had normal background activity. All patients were treated with divalproex monotherapy. Five patients have been seizure free, and one had a single breakthrough GTC seizure during a follow-up period of 12-36 months. CONCLUSIONS: GTC activity may evolve from typical absence seizures. This seizure type should be included in the International Classification of Seizures. Its recognition and distinction from complex partial seizures with secondary generalization are important for appropriate therapy.     

Predicting seizure frequency after epilepsy surgery

OBJECTIVE: To identify clinical features related to seizure frequency after epilepsy surgery in patients with recurrent seizures. BACKGROUND: No studies have examined the differences between patients who have rare seizures and patients who experience frequent seizures after epilepsy surgery. Since seizure frequency correlates with morbidity and quality of life, it is desirable to know which preoperative clinical features predict postoperative seizure frequency. METHODS: Patients with recurrent seizures were placed in two categories: rare postoperative seizures (< or =2 per year) and frequent postoperative seizures (> or =12 per year) using seizure frequency in the second postoperative year. Variables included preoperative seizure frequency, age of first risk, age at first seizure, epilepsy duration, age at surgery, history of febrile convulsions, tonic-clonic seizures, status epilepticus, or family history, IQ, magnetic resonance imaging (MRI), and positron emission tomography (PET). Variables were analyzed using non-parametric tests to assess relationship to postoperative seizure frequency. RESULTS: Of 475 patients who had epilepsy surgery, 111 had rare or frequent seizures in the second postoperative year. After anterior temporal lobectomy (ATL), age of first risk< or =5 years and presence of mesial temporal sclerosis on MRI were associated with rare seizures (66% of patients), whereas lack of these risk factors was associated with frequent seizures (75% of patients) (p<0.03). For non-ATL operations, preoperative seizure frequency of > or =20 seizures per month was associated with frequent postoperative seizures (p=0.03). No other variables influenced outcome. CONCLUSIONS: Some preoperative clinical features correlate with postoperative seizure frequency in patients with recurrent seizures after epilepsy surgery. This has implications for the surgical decision making process and early postoperative management.     

Falsely localizing ictal onsets with depth EEG telemetry during anticonvulsant withdrawal

A patient with partial complex seizures evaluated for surgery with chronic depth electrode recordings demonstrated falsely localizing ictal onsets during anticonvulsant drug withdrawal. When phenytoin was being reduced, more seizures appeared to originate from the left temporal lobe than from the right. Right anterior temporal lobectomy, performed on the basis of other findings, revealed a small unsuspected tumor in the resected specimen, and the patient has remained seizure free for 3 years. The seizures that originated from the left temporal lobe were different from the patient's habitual attacks and appeared to be the result of anticonvulsant withdrawal and, perhaps, electrode irritation. Four other patients who received anterior temporal lobectomies at UCLA between 1977 and 1980 had at least one stereotaxic EEG (SEEG)-recorded contralateral seizure onset, and all have benefited from surgery. Although multifocal SEEG-recorded ictal onsets should be considered a poor prognostic sign, distant sites that give rise to atypical seizures during drug withdrawal may not generate spontaneous seizures postoperatively. Consequently, this finding should not be used as a sole criterion against the recommendation of surgical therapy.     

Management of antiepileptic drugs following epilepsy surgery: a review

The favourable impact of surgery for intractable epilepsy on seizures is well documented. However, few studies have determined what changes in antiepileptic drug (AED) therapy occur following surgery. Alterations in AED blood levels in the immediate postoperative period can result in breakthrough seizures. In long term follow-up, one-third to one-half of seizure-free patients after temporal lobectomy, the most common type of epilepsy surgery, still require AED treatment which usually has been reduced from polytherapy to monotherapy. In our study of 93 patients followed two years after temporal lobectomy, polytherapy decreased from 78% before surgery to 14% postoperatively, while medication was discontinued in 44%. Early reduction from polytherapy to monotherapy can often be carried out in the immediate postoperative period but the most appropriate timing of cessation of AED treatment has yet to be determined. Patients undergoing extratemporal resections and other forms of epilepsy surgery associated with less favourable postoperative seizure control may achieve comparatively less reduction in antiepileptic medication. We generally do not recommend stopping AEDs prior to one year after surgery.     

Long-term seizure outcome and risk factors for recurrence after extratemporal epilepsy surgery

Purpose: We aimed to assess long‐term seizure outcome and risk factors for seizure recurrence in a cohort of patients who have undergone extratemporal resection for management of refractory seizures. Methods: Eighty‐one patients underwent extratemporal resection at Austin Health, Melbourne, Australia (1991–2004). Seizure recurrence was any postoperative disabling seizure (complex partial seizure [CPS] ± secondary generalization). Multivariate Cox proportional hazards regression models examined potential preoperative and perioperative risk factors and the risk associated with early postoperative seizures (≤28 days postsurgery). The change between preoperative and postoperative seizure frequency was also measured. Key Findings: Median follow‐up was 10.3 years (range 1–17.7). The probabilities of freedom from disabling seizures (on or off antiepileptic medication) were 40.7% (95% confidence interval [CI] 30–51) at 1 month, 23.5% (95% CI 15–33) at 1 year, and 14.7% (95% CI 8–23) at 5 years postoperative. Reduction of disabling seizures to at least 20% of preoperative frequency was attained by 57% of patients at 5 postoperative years. Of the preoperative/perioperative factors, focal cortical dysplasia (FCD) type 1 (hazard ratio [HR] 1.90, 95% CI 1.08–3.34, p = 0.025) and incomplete resection (HR 1.71, 95% CI 1.06–2.76, p = 0.028) were independent recurrence risks. After surgery, an early postoperative seizure was the only factor associated with higher risk (HR 4.28 [2.42–7.57], p = 0.00). Significance: Distinction between subtypes of focal cortical dysplasia, which can be made using magnetic resonance imaging (MRI) criteria, may be useful for preoperative prognostication. Early seizures after surgery are not benign and may be markers of factors that contribute to seizure recurrence. Most patients achieve substantial reduction in seizure frequency. Further study of the significance of this reduction in terms of surgical “success” or otherwise is required.     

Wisconsin Card Sorting performance in patients with temporal lobe epilepsy: clinical and neuroanatomical correlates

PURPOSE: A sizable proportion of patients with temporal lobe epilepsy (TLE) display impairments on tests of executive function. Previous studies have suggested several factors that may explain such performance, including the presence of hippocampal sclerosis, electrophysiological disruption to extratemporal regions, and early age of seizure onset. However, no clear determinants have been found that consistently explain such executive dysfunction. The present study investigated the contribution of several clinical variables and temporal lobe neuroanatomic features to performance on the Wisconsin Card Sorting Test (WCST) in a series of patients with TLE. METHODS: Eighty-nine patients with lateralized TLE (47 left, 42 right) were examined. Seventy-two patients from this series underwent anterior temporal lobectomy (ATL). Regression analysis was used to examine the effects of age, education, age at seizure onset, seizure duration, seizure laterality, history of secondary generalized seizures, and MRI-based volumes of the right and left hippocampi on preoperative WCST performance (number of categories completed, perseverative errors). Further univariate analyses examined whether the presence of bilateral hippocampal sclerosis, mesial temporal lobe abnormalities beyond the hippocampus, or temporal neocortical abnormalities affected preoperative WCST performance. In addition, we examined whether becoming seizure free after ATL affected change in WCST performance. RESULTS: Overall regression analysis was not significant. However, an examination of individual partial correlations revealed that patients with a history of secondary generalized seizures performed more poorly on the preoperative WCST than did patients without such history. In addition, patients who were seizure free after ATL did not exhibit better WCST outcome than patients who did not become seizure free. The presence of bilateral hippocampal sclerosis, extrahippocampal mesial temporal atrophy, or temporal neocortical lesions did not affect WCST performance. CONCLUSIONS: These results indicate that the presence of temporal lobe structural abnormalities do not significantly affect executive function as measured by the WCST. The present study does suggests that the critical determinants of WCST performance in patients with TLE lie outside the temporal lobe and likely relate to metabolic disruption to frontostriatal neural network systems.     

Factors That Preclude the Successful Use of Monopharmacy in the Medical Treatment of Patients with Epilepsy

Abstract: A neurologist conducted research efforts for more than 12 years as a step toward the establishment of monotherapy for epilepsy. Of 406 patients with epilepsy, seizures could be controlled for more than one year in 72% and for more than 3 years in 54%. Monotherapy was given to 57% of all the patients with a success rate of 54%. Factors that were found likely to interfere with a reduction in antiepileptic drug therapy to one drug modality included: symptomatic etiology, prolonged duration of illness, low age at onset and secondary generalized epilepsy with a large number of seizures in combination, for generalized epilepsies; symptomatic etiology, prolonged duration of illness, low age at onset, other than occipital lobe origin, complex partial seizure with secondary generalization, temporal lobe epilepsy with associated automatisms, elementary sensorimotor seizure and high frequency of seizures, for partial epilepsies. In addition to these factors relevant to the nature of epilepsies, other factors apparently unrelated to the disease process, e.g., liability of polypharmacy to produce side effects precluding dosage elevation, patient's rejection to reduce drug and the inability of a physician to treat the patient properly for want of information, were also recognized to exist.     

Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy

Sedative-hypnotic antiepileptic drugs have potentially toxic effects, but their removal is often thought to be difficult and dangerous. We completely withdrew all barbiturates and benzodiazepines from 78 patients with intractable epilepsy (48 inpatients and 30 outpatients). Initially, 19 patients had plasma levels of sedative drugs above the therapeutic range; 28 were taking more than one of these drugs. Dosages of nonsedative antiepileptic drugs were adjusted to provide optimal seizure control. After 6 months of outpatient follow-up, 69 patients remained on a nonsedative regimen: 35 (51%) showed improvement in both drug toxicity and seizure control, 13 (19%) in toxicity alone, 8 (12%) in seizure control alone; 12 (16%) were unchanged, and 1 was worse. Of 9 patients restarted on sedative antiepileptic drugs by their private physicians, 4 had more toxic symptoms than at discharge, 1 had more frequent seizures, 3 were unchanged, and 1, who had had a temporal lobectomy after drug withdrawal, had less frequent seizures. Sedative drugs are not necessary for optimal seizure control, even in intractable epilepsy, and they may be safely withdrawn.     

Seizure control and cognitive outcome after temporal lobectomy: a comparison of classic Ammon's horn sclerosis,atypical mesial temporal sclerosis,and tumoral pathologies

PURPOSE: Neuropathologic examination of resected tissue after anterior temporal lobectomy (ATL) for treatment of complex partial seizures revealed several distinct histologic substrates. Our study examined the relation between neuropathology, seizure control, and cognition in ATL patients and described preliminary profiles to aid in the prediction of outcome. METHODS: Of the 149 patients who underwent ATL from 1980 to 1999, long-term follow-up was available for 145. Specimens from 124 of the 145 patients had histologic findings consistent with one of three diagnoses: classic Ammon's horn sclerosis (cAHS; n = 75), atypical mesial sclerosis (Atypical; n = 21), or low-grade tumor (Tumor; n = 28). The other 20 patients had diverse pathologies that were insufficient for analysis. ATL patients underwent a complete preoperative and 68 underwent a postoperative neuropsychological evaluation. RESULTS: Of the 145 patients, 84% of cAHS, 57% of Tumor, and 29% of Atypical patients had a > or =95% reduction in seizure frequency. Neuropsychological testing suggested that cAHS patients demonstrate more generalized preoperative cognitive impairment than do the Atypical or Tumor patients. The Atypical group recalled significantly less nonverbal material after surgery than did the cAHS or Tumor groups. Stratification by both pathology and surgery side revealed that the right Atypical patients declined more on information processing and set shifting. CONCLUSIONS: Patients with cAHS or Tumor demonstrated better seizure control and fewer declines in cognitive functioning after ATL than did the Atypical patients, highlighting the need to investigate this group as a distinct entity.     

Long-term seizure outcome and its predictors in patients with recurrent seizures during the first year aftertemporal lobe resective epilepsy surgery

Purpose: The existing data on the implications of the characteristics of seizures that recur during the first year following epilepsy surgery on subsequent seizure outcome are conflicting. We investigated the impact of recurrent seizures in the first postoperative year and their attributes on long‐term seizure outcome. Methods: We studied the postoperative courses of 492 patients who had completed two or more years of follow‐up after temporal lobe resective epilepsy surgery. We used Kaplan‐Meier survival curves to define long‐term seizure outcome and assessed the predictive value of recurrent seizure characteristics on the outcome by univariate and multivariate proportional hazards regression models. Key Findings: In our patients, seizure recurrences during the first postoperative year, irrespective of the attributes of recurrent seizures (such as provoked vs. unprovoked, and timing and number of recurrences), imparted fourfold to sevenfold increased hazards for continued seizures beyond the first postoperative year. Although patients with complex partial seizures with or without secondary generalized tonic–clonic seizures (CPS/GTCS) had a sixfold increased risk, those with auras alone had only a borderline risk for seizures beyond the first postoperative year. In the multivariate model, CPS/GTCS as the predominant seizure type and three or more seizure recurrences during the first postoperative year independently predicted unfavorable long‐term seizure outcome. Significance: Our study provides valuable information that is helpful in prognosticating and counseling patients, and in making rational decisions on the withdrawal of antiepileptic drugs following surgery. Our findings enhance the general understanding of the etiopathogenesis of surgical failure.     

Preoperative FDG-PET temporal lobe hypometabolism and verbal memory after temporal lobectomy

OBJECTIVE: To examine the relationship of preoperative fluorodeoxyglucose (FDG)-PET asymmetry in temporal lobe metabolism and memory outcome after anterior temporal lobectomy (ATL). METHODS: In a university-based epilepsy surgery center, 60 ATL patients (27 left, 33 right) were divided into two groups: no/mild (n = 21) or moderate/ severe (n = 39) asymmetry in temporal lobe hypometabolism as determined by FDG-PET. All patients were nonretarded, at least 18 years of age, left-hemisphere speech dominant, without MRI abnormalities other than hippocampal atrophy, and with unilateral temporal lobe origin of intractable complex partial seizures. Neuropsychological measures of intelligence and verbal and visual memory function were assessed preoperatively and 6 months postoperatively. RESULTS: Left ATL patients with no/mild asymmetry in FDG-PET temporal lobe metabolism exhibited significantly greater verbal memory decline compared with left ATL patients with moderate/severe hypometabolism. There was no significant relationship between PET asymmetry and pre- to postsurgical IQ change. No significant relationship was observed between extent of PET hypometabolism and memory outcome for right ATL patients. CONCLUSIONS: FDG-PET asymmetry can be added to the preoperative clinical markers that appear useful in predicting verbal memory decline after left ATL.     

Factors that preclude the successful use of monopharmacy in the medical treatment of patients with epilepsy

A neurologist conducted research efforts for more than 12 years as a step toward the establishment of monotherapy for epilepsy. Of 406 patients with epilepsy, seizures could be controlled for more than one year in 72% and for more than 3 years in 54%. Monotherapy was given to 57% of all the patients with a success rate of 54%. Factors that were found likely to interfere with a reduction in antiepileptic drug therapy to one drug modality included: symptomatic etiology, prolonged duration of illness, low age at onset and secondary generalized epilepsy with a large number of seizures in combination, for generalized epilepsies; symptomatic etiology, prolonged duration of illness, low age at onset, other than occipital lobe origin, complex partial seizure with secondary generalization, temporal lobe epilepsy with associated automatisms, elementary sensorimotor seizure and high frequency of seizures, for partial epilepsies. In addition to these factors relevant to the nature of epilepsies, other factors apparently unrelated to the disease process, e.g., liability of polypharmacy to produce side effects precluding dosage elevation, patient's rejection to reduce drug and the inability of a physician to treat the patient properly for want of information, were also recognized to exist.     

Factors related to successful antiepileptic drug withdrawal after anterior temporal lobectomy for medial temporal lobe epilepsy.

OBJECTIVE: To assess the rate of successful antiepileptic drug (AED) discontinuation, prognostic factors and proper time of AED withdrawal after surgery for medial temporal lobe epilepsy (MTLE). METHODS: We reviewed 171 consecutive patients who underwent resective surgery for MTLE. All patients were followed up for more than two postoperative years. AEDs were slowly tapered with an individualized schedule for each patient. Outcome status was determined from medical records and telephone interviews. RESULTS: 41.2% of patients experienced no seizure recurrence. 34.5% discontinued medication without seizure recurrence for more than 2 years at final assessment. Multivariate analysis revealed that an age greater than 30 years at surgery and postoperative AED reduction before 10 months increased the risk of recurrence [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.1-3.9 and HR 2.5, CI 1.1-5.8]. CONCLUSIONS: Resective surgery for MTLE brings seizure remission without AED to one-third of patients. Postoperative AED tapering is recommended after at least 10 months. Younger age at surgery is a good predictive factor of remission after MTLE surgery.     

Limitations in the Medical Treatment of Cryptogenic or Symptomatic Localization-Related Epilepsies of Childhood Onset

Summary: We retrospectively examined 169 patients who had cryptogenic or symptomatic localization-related epilepsies (LRE) and were followed-up for more than 5 years. The probability of seizure control was 0.13 during the first year of treatment, 0.25 during the first 5 years, and 0.09 during the second and third 5 years. No patients who continued to have intractable seizures for 15 years became free of seizures. The onset of LRE at the age of 3 years or less, seizure cluster, mesial temporal sclerosis (MTS), and temporal lobe epilepsy (TLE) were significantly associated with a poor seizure control. If an antiepileptic drug (AED) failed to control seizures, probability of seizure control by the next drug was low, in particular in patients in whom more than 4 AEDs have already been tried, and seizure control could not be expected after a trial of 6 AEDs. A tentative indication of epilepsy surgery for LRE of childhood onset may be 5 years of poor seizure control and/or failure of four AEDs.     

Refractory grand mal seizures with onset during infancy including severe myoclonic epilepsy in infancy.

In 1978, Dravet proposed a clinical entity called severe myoclonic epilepsy in infancy (SMEI). In the same year, a patient group, which was later called high voltage slow wave-grand mal syndrome (HVSW-GM), is reported in Japan. Both syndromes are very similar, except for seizure manifestation: generalized tonic-clonic convulsions (GTC) with myoclonic and other polymorphic seizures in SMEI vs. GTC only in HVSW-GM. To study the pathophysiology of these refractory epilepsies, the author formulated new clinical diagnostic criteria common to both syndromes as follows: GTC with onset before the age of 1 year as the principal seizure type; an epilepsy entity unclassifiable either as partial or generalized by all the clinical data including EEG findings; mental and motor dysfunction absent prior to seizure onset but appearing later; absence of epileptiform activities on EEG in the initial stage; stubborn refractoriness to conventional antiepileptic medication. Twenty-two patients meeting all of five clinical criteria above mentioned were recruited in the study. Detailed analysis of clinico-electrical features and long-term follow-up of these patients led the author to the conclusion that GTC in combination with seizures of other types will contribute to an unfavorable pathophysiological or prognostic conditions, and, especially when GTC exists in combination with myoclonic seizures, the severity of epilepsy will increase. The author claimed that the three clinical entities, SMEI, HVSW-GM, and their variant form, share certain characteristics in common and may constitute a unique epilepsy syndrome for which a new name of infantile refractory grand mal syndrome (IRGMS) was offered. This is a more basic concept with broader spectrum than SMEI, encompassing not only SMEI but also related borderlands like HVSW-GM. More recently, the author observed that early zonisamide medication within 1 year after seizure onset may improve seizure prognosis in IRGMS, by preventing the development of myoclonic seizures.