From the American Epilepsy Society 2009 Annual Course. Non-substrate-directed epilepsy and surgery: PRO and CON.

The surgical treatment of epilepsy is the most efficacious therapeutic modality for patients with a medically refractory partial seizure disorder. Epilepsy surgery has been demonstrated to be both effective and well tolerated in individuals with medial temporal lobe epilepsy associated with mesial temporal sclerosis. The identification of an MRI pathological substrate may be useful in identifying the epileptogenic zone and the appropriate operative strategy, and is predictive of the long-term seizure outcome. Patients with a non-substrate-directed partial epilepsy often require a more rigorous presurgical evaluation because of issues regarding the lateralization and localization of the epileptic brain tissue. The surgical outcome may be most disappointing in individuals with localization-related epilepsy of extratemporal origin associated with a normal MRI study. The present discussion focuses on the selection of patients with extratemporal non-substrate-directed epilepsy for a presurgical evaluation. The important factors associated with an improved quality of life subsequent to epilepsy surgery include seizure remission and avoidance of operation-induced adverse effects.

Psychiatric co-morbidity in 75 patients undergoing epilepsy surgery: lack of correlation with pathological findings.

BACKGROUND: Psychiatric disorders may occur in patients with intractable partial epilepsy after surgical treatment. Previous reports attributed the presence of psychological adverse events to specific pathological entities such as dysembryoplastic neuroepithelial tumors (DNETs) and gangliogliomas. The rationale for the present study is to evaluate the importance of the surgical pathology in individuals undergoing epilepsy surgery. METHODS: The patients were separated into three groups based on the surgical pathology: group I ganglioglioma (N=25), group II DNETs (N=25), and group III mesial temporal sclerosis (N=25). Thirteen of the 75 patients (17.3%) had a preexisting psychiatric disorder. The most common preoperative psychiatric diagnosis was depression (N=4). Sixty-three of the lesions (84%) were restricted to the temporal lobe. The operative strategy included resection of the lesion and epileptogenic cortex. Sixty-two of the 75 patients (83%) were rendered seizure-free. RESULTS: Eight of the 75 patients (10.7%) had an acquired psychiatric illness following surgical treatment. A mood disorder developed in three patients after surgery. No statistical difference emerged in preoperative psychiatric co-morbidity (no group difference; p=1.0) or in newly diagnosed postoperative psychiatric disease (group I vs. II, p=0.67; group I vs. III, p=1.0; and group II vs. III, p=0.67) within the three surgical pathology groups. CONCLUSION: This study indicates that the presence of psychiatric disease before and after surgery for intractable partial epilepsy, predominantly of temporal lobe origin, was independent of the pathological findings.

Partial epilepsy presenting as focal paroxysmal pain.

A 3-year old, previously well child developed paroxysms of left thigh pain. Evaluation was unremarkable except for interictal and postictal EEG epileptiform activity in the right parietal and posterior temporal regions. The painful spells were controlled with anticonvulsant medication. Episodes of paroxysmal, unexplained pain may rarely be the initial clinical manifestation of a partial seizure disorder.

Brainstem auditory hallucinosis.

We studied three patients with findings suggesting that auditory hallucinations may occur with lesions of the tegmentum of the pons and lower midbrain. The evidence was clinical (indicating location of the lesion), radiologic (CT), pathologic in one case, and physiologic (affirming integrity of the cochleas and auditory nerves). The condition is comparable with the Lhermitte peduncular-diencephalic visual hallucinosis.

Hippocampal sclerosis without detectable hippocampal atrophy.

Six patients from three centers had MRI and pathologic evidence of hippocampal sclerosis but no detectable hippocampal atrophy. Loss of normal internal structure and T1- and T2-weighted signal abnormalities allowed the MRI diagnosis of unilateral hippocampal sclerosis when hippocampal volume measurements were normal and symmetric. Although accurate hippocampal volume measurements will determine the most severely affected side in most cases, volume measurements or atrophy alone will not always detect all MRI-visible pathology. Additional detailed MRI assessment is required before structural abnormality of the hippocampus is excluded on the basis of volume measurements.

Unusual viral causes of transverse myelitis: hepatitis A virus and cytomegalovirus.

Twenty to 40% of cases of acute transverse myelitis are attributed to viral infections, although the specific viral etiology is only rarely identified. We studied two patients with transverse myelitis in association with acute hepatitis A virus (HAV) infection and acute primary cytomegalovirus (CMV) infection. This is the first well-documented report of an association between HAV infection and transverse myelitis, and only the fourth documented case of transverse myelitis in association with CMV infection in an immunocompetent adult. Both viruses should be considered as rare causes of transverse myelitis in immunologically normal adults.

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.

Evoked potentials in motor system diseases.

We studied pattern-shift visual (PSVEP), brainstem auditory (BAEP), and somatosensory (SEP) evoked potentials in 38 unselected patients with motor system diseases (MSD) (28 sporadic, 10 familial). PSVEPs were normal in all patients, and BAEPs were normal in all except one with clinical hearing loss who had absent waves I and III and prolonged wave V latencies. Median and tibial SEPs revealed definite CNS conduction abnormalities in only 1 of 30 and 1 of 18 patients, respectively. In addition, four patients had peripheral and four had peripheral or central delays on tibial nerve testing. There were no or only small group differences in central conduction SEP, BAEP, and PSVEP values in patients with normal studies compared with controls. This study suggests that central conduction SEP, BAEP, or PSVEP abnormalities can rarely be attributed to MSD and that their presence in patients suspected of having this disorder should prompt a search for an alternative diagnosis.

Gadolinium-DTPA-enhanced magnetic resonance imaging in intractable partial epilepsy.

We performed magnetic resonance imaging (MRI), before and after the administration of gadolinium-DTPA (Gd-DTPA), in 23 patients with medically refractory partial epilepsy who subsequently had surgical treatment for their seizure disorder. In most patients, 61%, unenhanced and enhanced MRI studies were negative. In 26% the unenhanced image was positive, and the abnormality enhanced with Gd-DTPA. In 13% the unenhanced MR image was positive, but the abnormality did not enhance with Gd-DTPA. Gd-DTPA does not appear to increase the diagnostic yield of MRI in the presurgical evaluation of patients with partial epilepsy if the unenhanced MRIs are normal.

Surgery for focal epilepsy in the older patient.

Eight of the 237 patients who received a surgical procedure for intractable partial epilepsy at the Mayo Clinic during a 3-year period were 50 years of age or older. All patients had disabling partial seizures of several years in duration that were refractory to antiepileptic drug medication. A neuroimaging-identified epileptogenic lesion prompted referral for surgical treatment in three patients. The only clinically significant morbidity associated with surgery in the eight patients was a transient exacerbation of an aphasia in a patient who underwent a left frontal corticectomy. All eight patients had a favorable seizure outcome, and three patients postoperatively are seizure free. Epilepsy surgery may be an appropriate alternate therapy for select patients in the sixth decade of life or older with medically refractory partial seizures.

Long-term mortality after a first episode of status epilepticus.

OBJECTIVE: To evaluate long-term mortality among people with status epilepticus (SE). METHODS: The authors performed a population-based retrospective cohort study to determine long-term mortality after SE. Between January 1, 1965, and December 31, 1984, all first episodes of SE receiving medical attention were ascertained through the Rochester Epidemiology Project Records-Linkage System. Cases surviving the first 30 days (n = 145) were followed until death or study termination (February 1996). RESULTS: At 10 years, cumulative mortality among 30-day survivors was 43%. The standardized mortality ratio (SMR) at 10 years was 2.8 (95% CI, 2.1-3.5). The mortality rate of those with idiopathic/cryptogenic SE was not increased (SMR = 1.1; 95% CI, 0.5-2.3). The following characteristics of SE increased long-term risk for mortality: SE > or = 24 hours in duration vs. SE < 2 hours (relative risk [RR] = 2.3; 95% CI, 1.1-5.1); acute symptomatic etiology vs idiopathic/cryptogenic etiology (RR = 2.2; 95% CI, 1.0-5.1) SE; myoclonic SE vs generalized convulsive SE (RR = 4.0; 95% CI, 1.3-13). CONCLUSION: Forty percent of subjects who survived the first 30 days after an incident episode of SE die within the next 10 years. The long-term mortality rate was threefold that of the general population over the same time period. The long-term mortality rate at 10 years was worse for those with myoclonic SE, for those who presented with SE lasting more than 24 hours, and for those with acute symptomatic SE. The long-term mortality rate was not altered in those with idiopathic/cryptogenic SE. We conclude that SE alone does not modify long-term mortality.

Incidence and clinical consequence of the purple glove syndrome in patients receiving intravenous phenytoin.

OBJECTIVE: To determine the incidence, risk factors, and long-term sequelae of the purple glove syndrome (PGS) in hospital patients receiving IV phenytoin. BACKGROUND: PGS is a poorly understood, potentially serious local complication of IV phenytoin administration characterized by progressive distal limb edema, discoloration, and pain. METHODS: The pharmacologic records of the Mayo Foundation hospitals were reviewed to identify 179 consecutive patients who had IV phenytoin ordered during a 3-month period. Their hospital records were then reviewed to confirm IV phenytoin treatment, the frequency of PGS (defined as the progressive development of edema, discoloration, and pain in the limb after administration of IV phenytoin), and the outcome of PGS. RESULTS: A total of 152 patients received IV phenytoin, and nine (5.9%) developed PGS. PGS patients received a greater median initial dose of phenytoin, total 24-hour dose, and total number of doses (all p < 0.05). In addition, the median age of the PGS patients was older, their infusion was more often given for acute seizures, it was less likely to be administered in the operating room, and the length of their hospital stay was longer (all p < 0.05). One patient required surgical therapy, and all other patients resolved within 3 weeks with conservative management. CONCLUSIONS: PGS is not rare and elderly patients and individuals receiving large, multiple doses are particularly at risk. This iatrogenic complication may be preventable by substituting fosphenytoin for IV phenytoin.

MRI assessments of hippocampal pathology in extratemporal lesional epilepsy.

We performed a prospective study in 18 patients to determine the extent of MRI-identified hippocampal pathology in patients with intractable partial epilepsy of extratemporal origin. A mesial temporal signal-intensity alteration or hippocampal formation (HF) atrophy, or both, have been shown to be reliable markers of the temporal lobe of seizure origin in patients with mesial temporal sclerosis. All patients subsequently received surgical ablative therapy between 1988 and 1992. During shortterm follow-up, 14 of the 18 patients experienced a significant reduction in seizure tendency, and 12 patients were rendered seizure-free. Qualitative and quantitative (HF volumetry) assessments of HF pathology were performed retrospectively by a blinded investigator. No hippocampal imaging alteration was present in 17 patients. Left HF atrophy was confirmed in one patient with post-traumatic epilepsy who underwent a successful right frontal lobectomy. Morphometric MRI studies rarely identify hippocampal pathology in patients with extratemporal epilepsy.

Facial asymmetry, hippocampal pathology, and remote symptomatic seizures: a temporal lobe epileptic syndrome.

We performed a prospective study of neuroimaging studies and temporal lobe pathology in 13 patients with facial asymmetry and intractable partial epilepsy of temporal lobe origin. The 13 patients, derived from 50 consecutive patients with nonlesional medically refractory partial epilepsy, were deemed appropriate candidates for an anterior temporal lobectomy. The facial weakness occurred exclusively, or was most prominent, during emotional expression, ie, spontaneous smiling. The temporal lobe of seizure origin, demonstrated by ictal long-term EEG monitoring, was always contralateral to the side of weakness. All 13 patients had a history of early childhood neurologic disease, eg, complex febrile seizure or bacterial meningitis. Hippocampal formation atrophy was present in all the epileptic temporal lobes by MRI-based volume studies. Twelve of the 13 patients subsequently received an anterior temporal lobectomy, and mesial temporal sclerosis was present in all the surgically excised temporal lobes. Ten of the 12 patients have been seizure-free during short-term follow-up. Facial asymmetry may occur in patients with partial epilepsy related to remote symptomatic seizures and mesial temporal sclerosis.

Comparative diagnostic utility of 1H MRS and DWI in evaluation of temporal lobe epilepsy.

OBJECTIVE: To compare the ability of diffusion-weighted MRI (DWI) and (1)H MRS to lateralize to the temporal lobe of seizure onset and to predict postoperative seizure control in patients with temporal lobe epilepsy (TLE). METHODS: Forty TLE patients who subsequently underwent epilepsy surgery and 20 normal subjects were studied with (1)H MRS and DWI. Medial parietal and temporal lobe N-acetylaspartate (NAA)/creatine (Cr) ratios and hippocampal and temporal stem apparent diffusion coefficients (ADC) were obtained. Lateralization to either temporal lobe with each MR measurement was based on the threshold values derived from +/-1-SD right/left ratios of normal subjects. RESULTS: Temporal lobe NAA/Cr lateralized to the operated temporal lobe in 18 of 40 (45%), hippocampal ADC in 32 of 40 (80%), and temporal stem ADC in 26 of 40 (65%) patients. Almost all of the cases that lateralized to the surgical side with NAA/Cr ratios (94%) had an excellent postoperative seizure control (p = 0.01). Lateralization to the side of surgery was not associated with surgical outcome with hippocampal and temporal stem ADC (p > 0.05). CONCLUSION: (1)H MRS and DWI complement each other in the clinical setting. DWI more frequently lateralized to the operated side, and (1)HMRS was a better predictor of postoperative seizure control.

Population-based study of the incidence of sudden unexplained death in epilepsy.

OBJECTIVE: To determine the population-based incidence of sudden unexplained death in epilepsy (SUDEP) and to determine the risk of SUDEP compared with the general population. BACKGROUND: Prior studies of SUDEP have described a wide range of incidence and have suffered from selection bias and other methodologic limitations. A population-based study of the incidence of SUDEP has never been performed. Furthermore, the risk of sudden death in the epilepsy population has not been compared with that of the general population. METHODS: All deaths in persons whose epilepsy was diagnosed between 1935 and 1994 in Rochester, MN, were reviewed. The rate of SUDEP was compared with the expected rate of sudden death in the general population for patients age 20 to 40 years to determine the standardized mortality ratio (SMR). RESULTS: We identified nine cases of SUDEP. SUDEP accounted for 8.6% (7 of 81) of the deaths in persons 15 to 44 years of age. The incidence of SUDEP was 0.35 per 1,000 person-years. SMR for SUDEP was 23.7 (95% confidence interval, 7.7 to 55.0) compared with the general population. CONCLUSIONS: The incidence of SUDEP in our study was 0.35 per 1,000 person-years. SUDEP was responsible for 1.7% of deaths in our cohort. SUDEP is a rare cause of death in the epilepsy population but exceeds the expected rate of sudden death in the general population by nearly 24 times.

Predictors of outcome of anterior temporal lobectomy for intractable epilepsy: a multivariate study.

OBJECTIVE: To identify presurgical and postsurgical factors that are independently predictive of the outcome of anterior temporal lobectomy (ATL) for intractable epilepsy. BACKGROUND: There have been reports of prognostic factors in epilepsy surgery, but little is known about factors that independently predict outcome of ATL. METHODS: We studied 175 consecutive ATL patients who had at least 2 years of postsurgical follow-up. Significant factors on univariate analyses were subjected to stepwise logistic regression analysis. RESULTS: On univariate analyses, two presurgical conditions were significantly associated with excellent seizure control at last follow-up: (1) unilateral hippocampal formation atrophy as detected on MRI and (2) all scalp interictal epileptiform discharges concordant with the location of ictal onset (p < 0.05). Three postsurgical factors that occurred during the first year were associated with excellent seizure outcome: the absence of interictal epileptiform discharges at 3 months, complete seizure control, and having only nondisabling seizures for those who did not become seizure free. Logistic regression analysis revealed the following to be independently predictive of excellent seizure control: MRI-detected unilateral hippocampal formation atrophy, concordant interictal epileptiform discharges, complete seizure control during the first postsurgical year, and having only nondisabling seizures during the first postsurgical year for those who did not become seizure free. CONCLUSIONS: Presurgical identification of unilateral hippocampal formation atrophy, or of interictal epileptiform discharges that are all concordant with the location of ictal onset, predict excellent outcome of ATL. However, the probability of excellent outcome is highest (94%) when both factors are present.

Bilaterally symmetric hippocampi and surgical outcome.

This study investigates the relationship between hippocampal volume and seizure control following temporal lobectomy in patients with volumetrically symmetric hippocampi. Forty-six patients who underwent temporal lobectomy for nonlesional temporal-lobe-onset seizures, and in whom the volumes of the two hippocampi were roughly equal (ie, the difference of the right minus the left hippocampal volume fell between -0.1 and 0.3 cm3), were included. We graded postoperative seizure control on a four-point scale according to criteria defined by Engel. We found no relationship between the hippocampal sum (sum of the right plus left hippocampal volumes normalized for cranial size) and operative outcome. A satisfactory operative outcome is possible in patients with bilaterally symmetric mesial temporal sclerosis by MRI criteria.

Subtraction peri-ictal SPECT is predictive of extratemporal epilepsy surgery outcome.

OBJECTIVES: To determine whether localization of extratemporal epilepsy with subtraction ictal SPECT coregistered with MRI (SISCOM) is predictive of outcome after resective epilepsy surgery, whether SISCOM images provide prognostically important information compared with standard tests, and whether blood flow change on SISCOM images is useful in determining site and extent of excision required. BACKGROUND: The value of SISCOM in predicting surgical outcome for extratemporal epilepsy is unknown, especially if MRI findings are nonlocalizing. METHODS: SISCOM images in 36 consecutive patients were classified by blinded reviewers as "localizing and concordant with site of surgery," "localizing but nonconcordant with site of surgery," or "nonlocalizing." SISCOM images were coregistered with postoperative MRI, and reviewers visually determined whether cerebral cortex underlying the SISCOM focus had been completely resected, partially resected, or not resected. RESULTS: Twenty-four patients (66.7%) had localizing SISCOM, including 13 (76.5%) of those without a focal MRI lesion. Eleven of 19 patients (57.9%) with localizing SISCOM concordant with the surgical site, compared with 3 of 17 (17.6%) with nonlocalizing or nonconcordant SISCOM, had an excellent outcome (p < 0.05). With logistic regression analysis, SISCOM findings were predictive of postsurgical outcome, independently of MRI or scalp ictal EEG findings (p < 0.05). The extent of resection of the cortical region of the SISCOM focus was significantly associated with the rate of excellent outcome (100% with complete resection, 60% with partial resection, and 20% with nonresection, p < 0.05). CONCLUSION: SISCOM images may be useful in guiding the location and extent of resection in extratemporal epilepsy surgery.

Intractable nonlesional epilepsy of temporal lobe origin: lateralization by interictal SPECT versus MRI.

We performed a retrospective study of 53 consecutive "nonlesional" temporal lobectomy patients to assess the relative utility of MRI versus interictal single-photon emission computed tomography (SPECT) in this patient population. We compared the seizure lateralizing properties of MRI and SPECT using multiple blinded expert reviewers for both SPECT and MRI with a test-retest reviewer paradigm and measurements of hippocampal volume from MRI. The criterion standard for seizure lateralization was satisfactory postoperative seizure control (n = 43). The rate of correct seizure lateralization was significantly greater for MRI than for SPECT (p < or = 0.01), and the rate of incorrect lateralization was significantly less for MRI than for SPECT. The most accurate MRI measure was hippocampal volume measurements, which correctly lateralized the seizures in 86.0% of cases. The correct lateralization rate for SPECT was 45.4%. The MRI and SPECT studies tended to be noncomplementary with respect to seizure lateralization, and SPECT was likely to give an incorrect or indeterminate result in patients who were not lateralized by MRI. Concordant MRI-EEG lateralization was a strong predictor of satisfactory postoperative seizure control, while no relationship between postoperative seizure control and SPECT findings was present.