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.

Misdiagnosis of complex absence seizures.

Video-EEG monitoring disclosed absence seizures in five patients who were treated for partial seizures. Analysis of the historical and video data showed the presence of several potentially misleading ictal manifestations as follows: unidirectional head and/or eye turning, symmetric clonic activity, urinary incontinence, loss of balance causing injuries, focal clonic activity, and de novo automatisms. Without EEG correlation, complex absence seizures may be difficult to differentiate from other types of seizures. When correctly diagnosed, appropriate therapy may improve seizure control.

Cephalic fibromuscular dysplasia in 32 patients: clinical findings and radiologic features.

The clinical and angiographic features of 32 patients with cephalic fibromuscular dysplasia (FMD) are reported. All of our patients were women, 78% of whom were between 41 and 70 years of age. At examination, 18 (56%) patients had the sudden onset of focal ischemic neurologic deficits. Seven (22%) patients had intracranial berry aneurysms, which ruptured in five patients but were asymptomatic in two. The most common angiographic pattern was the "string of beads" deformity, which involved both extracranial internal carotid arteries at or distal to the third cervical vertebral level. The vertebral artery was affected in six cases, while three cases had intracranial involvement. Less common angiographic findings in this series consisted of segmental fusiform dilation of the artery, and lesions in the form of a septum that extended across the lumen. Twelve patients were followed up for an average of four years. Progression of FMD lesions was shown in two of the six patients who had repeated angiograms. The literature contains reports of only nine cases of cephalic FMD with repeated angiograms, three of which demonstrated progression. Our experience suggests a beneficial role for surgery in patients with specific symptoms in the distribution of the affected vessel, when coexistent disease is negligible or absent.

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.

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.

Prognosis of photoparoxysmal response in nonepileptic patients.

Photoparoxysmal response (PPR) is sometimes incidentally encountered in EEGs performed for evaluation of nonepileptic symptoms. We conducted the first long-term study of a cohort of nonepileptic patients to determine their risk of having seizures subsequent to incidental recording of PPR. After 6 to 12 years (mean, 9 years), none of the 33 patients had had epileptic seizures. To identify prognostic factors associated with PPR, we performed a case-control study comparing the cohort with 33 age-matched patients who had had epileptic seizures prior to PPR recording. There was no statistically significant difference between the two groups with respect to the clinical or EEG data. Morphology of the PPR discharge was not different between the two groups. Contrary to what is widely believed, persistence of PPR discharges beyond stimulation was not associated with a high risk of developing seizures. Prognosis of PPR is age-dependent and seems favorable in adults without previous epileptic seizures.

Population-based study of seizure disorders after cerebral infarction.

We performed the first population-based study that determined the magnitude of the risk and identified the factors predictive of developing seizure disorders after cerebral infarction. Five hundred thirty-five consecutive persons without prior unprovoked seizures were followed from their first cerebral infarctions until death or migration out of Rochester, Minnesota. Thirty-three patients (6%) developed early seizures (within 1 week), 78% of which occurred within the first 24 hours after infarction. Using multivariate analysis, the only factor predictive of early seizure occurrence was anterior hemisphere location of infarct (odds ratio 4.0; 95% CI 1.2 to 13.7). Twenty-seven patients developed an initial late seizure (past 1 week), whereas 18 developed epilepsy (recurrent late seizures). Compared with the population in the community, the risk during the first year was 23 times higher for initial late seizures and 17 times higher for epilepsy. The cumulative probability of developing initial late seizures was 3.0% by 1 year, 4.7% by 2 years, 7.4% by 5 years, and 8.9% by 10 years. Independent predictive factors on multivariate analysis for initial late seizures were early seizure occurrence (hazard ratio of 7.8 [95% CI 2.8 to 21.7]) and stroke recurrence (3.1 [1.2 to 8.3]). Both early seizure occurrence (16.4 [5.5 to 49.2]) and stroke recurrence (3.5 [1.2 to 10.5]) independently predicted the development of epilepsy as well. We also found that early seizure occurrence predisposed those with initial late seizures to develop epilepsy.

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.

Rapidly progressive hippocampal atrophy: evidence for a seizure-induced mechanism.

Hippocampal formation atrophy (HFA) developed in an adult, who did not have epilepsy previously, after the occurrence of new-onset partial seizures from acute thrombosis of an ipsilateral parietal venous angioma. There was no evidence of hippocampal injury, and the patient had only one brief, generalized tonic-clonic seizure. Although HFA progressed rapidly over 5.5 months, the partial seizures did not become prolonged or secondarily generalized. Evidence from the patient indicates that partial seizure activity can cause rapid and progressive hippocampal atrophy.

Subtraction SPECT co-registered to MRI improves postictal SPECT localization of seizure foci.

OBJECTIVE: To determine whether the detection of focal hypoperfusion by subtraction SPECT co-registered to MRI (SISCOM) improves the sensitivity and specificity of postictal SPECT in intractable partial epilepsy. BACKGROUND: Postictal SPECT injections are easier to perform than are ictal injections, but the images are more difficult to interpret and have been reported to have lower sensitivity and specificity. METHODS: Thirty-five consecutive intractable partial epilepsy patients who had postictal SPECT studies were evaluated. The following sets of SPECT images were separately interpreted by three blinded reviewers and classified as either localizing to 1 of 16 possible sites in the brain or as nonlocalizing: unsubtracted postictal and interictal images for conventional side-by-side comparison, SISCOM images of hyperperfusion, SISCOM images of hypoperfusion, and both sets of SISCOM hyperperfusion and hypoperfusion images (combined SISCOM evaluation). RESULTS: Significantly higher proportions of the hyperperfusion SISCOM images (65.7%), the hypoperfusion SISCOM images (74.3%), and the combined SISCOM evaluation (82.9%) were localizing than were the conventional method of side-by-side comparison of unsubtracted images (31.4%; p < 0.0001). Concordance with the discharge diagnosis was higher for the combined SISCOM evaluation than it was for either the hyperperfusion or the hypoperfusion SISCOM images alone (both p < 0.05). For the hypoperfusion SISCOM and the combined SISCOM evaluations, concordance of the localization with the site of epilepsy surgery was associated with a greater probability of an excellent outcome than were nonconcordant/nonlocalizing images (both p < 0.05). CONCLUSION: The use of SISCOM to detect focal cerebral hypoperfusion, in addition to focal hyperperfusion, improves the sensitivity and specificity of postictal SPECT in intractable partial epilepsy.

Temporal lobectomy for partial complex seizures: evaluation, results, and 1-year follow-up.

Twenty-six patients were evaluated for temporal lobectomy. Fourteen underwent initial monitoring with electrodes in the amygdala and hippocampus bilaterally. Twelve had initial monitoring with scalp and sphenoidal electrodes. Four had conclusive localization without depth electrodes. Twenty-three patients underwent lobectomy. At 1-year minimum follow-up, 15 were seizure free. Five had greater than 90% reduction in seizure frequency. Complications of depth electrodes were one hemorrhage and one abscess. One patient developed impaired memory following surgery. Temporal lobectomy is effective in well-selected patients. Depth electrodes localize seizure onset from mesial temporal structures. Scalp and sphenoidal recording may be sufficient in some cases.

Subtraction ictal SPECT co-registered to MRI improves clinical usefulness of SPECT in localizing the surgical seizure focus.

Traditional side-by-side visual interpretation of ictal and interictal single-photon emission computed tomography (SPECT) scans can be difficult in identifying the surgical focus, particularly in patients with extratemporal or otherwise unlocalized intractable epilepsy. Computer-aided subtraction ictal SPECT co-registered to MRI (SISCOM) may improve the clinical usefulness of SPECT in localizing the surgical seizure focus. We studied 51 consecutive intractable partial epilepsy patients who had interictal and ictal scans. The SPECT studies were blindly reviewed and classified as either localizing to 1 of 16 sites in the brain or as nonlocalizing. SISCOM images were localizing in 45 of 51 (88.2%) compared with 20 of 51 (39.2%) for traditional side-by-side inspection of ictal and interictal SPECT images (p < 0.0001). Inter-rater agreement for two independent reviewers was better for SISCOM (84.3% versus 41.2%, kappa = 0.83 versus 0.26; p < 0.0001). Concordance of seizure localization with the more established tests was also higher for SISCOM. Late injection of the radiotracer (> 45 seconds), but not secondary generalization of the seizure, was associated with a falsely localizing or nonlocalizing SISCOM. Epilepsy surgery patients whose SISCOM localization was concordant with a falsely localizing or nonlocalizing SISCOM. Epilepsy surgery patients whose SISCOM localization was concordant with the surgical site were more likely to have excellent outcome than patients with nonconcordant or nonlocalizing findings (62.5% [10/16] versus 20% [2/10]; p < 0.05). On the other hand, seizure localization by the traditional method of SPECT inspection had no significant association with postsurgical outcome. We conclude that SISCOM improves the sensitivity and the specificity of SPECT in localizing the seizure focus for epilepsy surgery. Concordance between SISCOM localization and site of surgery is predictive of postsurgical improvement in seizure outcome.

Dual-isotope SPECT using simultaneous acquisition of 99mTc and 123I radioisotopes: a double-injection technique for peri-ictal functional neuroimaging.

UNLABELLED: The acquisition of multiple radiotracer studies at different time points during a neurological event permits the study of different functional activation states in humans. Peri-ictal SPECT is a promising technique for localizing the epileptogenic zone and would be enhanced by the ability to acquire sequentially coregistered ictal and postictal SPECT images of a single seizure. This study was designed to develop and validate an accurate method for the simultaneous acquisition of 99mTc and 123I SPECT images of the brain. METHODS: A multicompartment, transaxial Hoffman brain-slice phantom was filled with 99mTc, 123I or a 3:1 mixture of the two isotopes. Planar and SPECT images were acquired by a dual-head gamma camera system equipped with parallel and fanbeam collimators, respectively. Thirty-two energy windows (2 keV width) were acquired over the energy range 120-184 keV. From the planar data, the signal-to-noise characteristics and crosstalk were measured for each energy window and used to devise an energy window acquisition strategy that was then applied to the SPECT data. Three summed energy windows were created: a primary 99mTc image (130-146 keV), a primary 123I image (152-168 keV) and a secondary 99mTc crosstalk image (134-140 keV). A fraction (0.041) of the 99mTc crosstalk image was subtracted from the 123I image. No crosstalk correction was performed on the primary 99mTc image. RESULTS: (a) Planar images: results showed 1.3% crosstalk in the 123I image compared with 19.7% for a 10% asymmetric energy window alone. 123I crosstalk into the 99mTc window was 2.79% and was relatively constant with changes in the location of the 99mTc energy window. (b) Tomographic images: results showed 1.51% 99mTc crosstalk in the 123I image compared with 12.44% for the uncorrected image and 3.70% 123I crosstalk in the 99mTc image. CONCLUSION: An effective technique for the simultaneous acquisition of 99mTc and 123I radiotracer distributions in the brain has been developed and validated in a phantom model and should have clinical application in peri-ictal functional activation studies of the brain.

Selection of antiepileptic drugs: a practical approach.

The selection of antiepileptic drugs (AEDs) is increasingly more complex as new agents become available. We discuss an individualized approach to selection of an AED that is tailored to each patient's needs by considering the following six factors: effectiveness of the drug in controlling seizures, adverse effects profile, pharmacokinetic properties, special or unique patient situations, drug interactions, and cost of treatment. When these factors are considered, treatment complications and failure can be minimized by anticipating incompatibilities among drugs or between the drugs and the patient's condition. We emphasize the concept that the best AED therapy is dependent on optimal seizure control and absence of unacceptable side effects. In the current environment of medical practice, the cost of treatment has also become a major concern. With rare exceptions, no single factor dictates the choice of an AED. In the long term, the most cost-effective treatment will be the one that provides the most therapeutic benefit with the fewest complications and maximal patient satisfaction.

A clinical approach to the classification of seizures and epileptic syndromes.

Seizures and epilepsies are heterogeneous. Their classifications are essential for clinicians to achieve a common understanding of the disorders. The diagnosis, treatment, and prognosis of seizure disorders depend on the correct identification of the types of seizures and epilepsy. The two currently accepted classifications are the International Classification of Epileptic Seizures and the International Classification of Epilepsies and Epileptic Syndromes. Both are based on clinical and electrophysiologic data, and both maintain a basic dichotomy between partial (focal, localization-related) and generalized epileptic disorders. Partial seizures are further classified into those that are simple partial, complex partial, and partial with secondary generalization. Generalized seizures are classified predominantly on the basis of their motor manifestations. Epilepsies are divided into idiopathic, cryptogenic, and symptomatic types. The utility and the limitations of these two classifications are discussed. A simplified system that encompasses neuroradiologic advances is offered to enhance the clinical usefulness of classifying epileptic disorders.

Psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (NES) are commonly encountered in clinical practice, and they may pose difficult diagnostic problems. For appropriate evaluation and treatment of NES, a multidisciplinary team approach is needed; typically, a neurologist with expertise in epilepsy, a psychologist or psychiatrist, and a support staff should be involved. Psychogenic NES have no single initial clinical manifestation, and various etiologic factors may contribute to their development. Of importance, psychogenic NES are "real" seizures that may be as disabling as epileptic seizures. Most often, they occur on a subconscious level, and the patient may have no control over their occurrence. Precipitation or termination of a habitual seizure during video-electroencephalographic monitoring has often been used to distinguish NES from epileptic seizures, but the results can sometimes be misleading. Numerous additional diagnostic techniques can be used to assist in making the diagnosis. Treatment is based on the type of psychiatric disorder present. Favorable prognostic factors include being female and having an independent lifestyle, normal electroencephalographic findings, higher intelligence, and no prior psychotherapy.