Long-term cognitive outcomes following out-of-hospital cardiac arrest: a population-based study.

OBJECTIVE: To report the neurologic outcomes in long-term survivors of out-of-hospital cardiac arrest with ventricular fibrillation as the presenting rhythm (OHCA VF) at a population level. METHODS: All adults who experienced OHCA VF in Olmsted County, MN, from 1990 to 2008, survived more than 6 months postarrest, and were alive at the time of study recruitment were invited to participate in structured neuropsychological testing and a neurologic examination. Cognitive test results were compared to the normal population using the Mayo's Older Adults Normative Studies. Linear regression models were fit to evaluate each neuropsychological test result in relation to call-to-shock time, sex, age at cardiac arrest, time elapsed since event, witnessed vs unwitnessed arrest, and administration of bystander cardiopulmonary resuscitation. RESULTS: Of 332 OHCA VF arrests, 140 people (42.2%, 95% confidence interval 36.9%-47.5%) survived to discharge. No patient entered a minimally conscious or permanent vegetative state. Long-term survivors (n = 47, median survival 7.8 years postarrest) had lower scores on measures of long-term memory and learning efficiency (p = 0.001) but higher than average scores on verbal IQ (p = 0.001). Nearly all survivors were functionally independent and scored high on the Mini-Mental State Examination (MMSE) (median Barthel Index 100/100, median MMSE 29/30). CONCLUSIONS: Long-term survivors of OHCA VF have long-term memory deficits compared to the normal population at the same age and education level. These findings provide a baseline for cognitive outcomes studies of OHCA VF as new techniques are developed to improve survival.

Neurologic manifestations in welders with pallidal MRI T1 hyperintensity.

BACKGROUND: Neurologic symptoms have been attributed to manganese fumes generated during welding. Increased T1 MRI signal in the basal ganglia is a biologic marker of manganese accumulation. Recent studies have associated welding and parkinsonism, but generally without MRI corroboration. OBJECTIVE: To characterize the clinical and neuropsychological features of patients with MRI basal ganglia T1 hyperintensity, who were ultimately diagnosed with neurotoxicity from welding fumes. METHODS: The medical records of welders referred to the Department of Neurology with neurologic problems and basal ganglia T1 hyperintensity were reviewed. RESULTS: All eight patients were male career welders with increased T1 basal ganglia signal on MRI of the brain. Several different clinical syndromes were recognized: a parkinsonian syndrome (three patients), a syndrome of multifocal myoclonus and limited cognitive impairment (two patients), a mixed syndrome with vestibular-auditory dysfunction (two patients), and minor subjective cognitive impairment, anxiety, and sleep apnea (one patient). Neuropsychometric testing suggested subcortical or frontal involvement. Inadequate ventilation or lack of personal respiratory protection during welding was a common theme. CONCLUSIONS: Welding without proper protection was associated with syndromes of parkinsonism, multifocal myoclonus, mild cognitive impairment, and vestibular-auditory dysfunction. The MRI T1 hyperintensity in the basal ganglia suggests that these may have been caused by manganese neurotoxicity.

The relationship between quantitative T2 relaxometry and memory in nonlesional temporal lobe epilepsy.

PURPOSE: We investigated the relationship between preoperative quantitative magnetic resonance imaging (MRI) T2 relaxometry and volumetry of the hippocampi and pre- and postoperative verbal memory in temporal lobectomy patients who had nonlesional temporal lobe epilepsy. METHODS: Pre- and postoperative memory data based on the Logical Memory (LM) subtest of the Wechsler Memory Scale-Revised (WMS-R) and the 30-min delayed recall trial of the Rey Auditory Verbal Learning Test (AVLT) were obtained from 26 left and 15 right temporal lobectomy patients. Coronal MRI T2 maps were generated for these 41 temporal lobectomy patients as well as 61 control patients. Hippocampal T2 relaxation times and hippocampal volumes, converted to z scores using control group data, were correlated with neuropsychological performance in the patients. RESULTS: In left temporal lobe-onset patients, high T2 in the left hippocampal body predicted higher LM performance after surgery. Asymmetrically high T2 in the left hippocampal body (i.e., the right-minus-left difference), compared with the right hippocampal body, also predicted higher LM performance after surgery. In right temporal lobe-onset patients, high T2 in the left hippocampal body predicted relatively lower AVLT performance after surgery. Multiple regression analysis in left temporal-onset patients revealed that high T2 in the left hippocampal body together with higher preoperative LM performance predict higher postoperative LM performance. CONCLUSIONS: Our findings suggest that elevated (i.e., abnormal) hippocampal T2 signal is associated with memory ability (or hippocampal functional capacity) independent of MRI-determined hippocampal atrophy. Therefore, our findings support the use of quantitative T2 relaxometry as an independent predictor of verbal memory outcome in both left and right TLE patients who are candidates for temporal lobectomy.

Temporal lobectomy in children: cognitive outcome.

OBJECT: The authors sought to determine the impact of early temporal lobectomy (in patients younger than age 17 years) on intellectual functioning. The efficacy of temporal lobectomy for treating seizures is well established and the procedure is becoming more acceptable as a treatment for children whose seizures are intractable. However, cognitive outcomes of temporal lobectomy in children and adolescents are largely unreported. The present study takes advantage of a unique multicenter collaboration to examine retrospectively intellectual functioning in a large sample of children who underwent temporal lobectomy. METHODS: Intellectual functioning was assessed before and after temporal lobectomy for treatment of medication-resistant seizures in 82 patients at eight centers of epilepsy surgery. All children underwent standard presurgical examinations, including electroencephalography-video monitoring, magnetic resonance (MR) imaging, and neuropsychological testing, at their respective centers. Forty-three children underwent left temporal lobectomy and 39 underwent right temporal lobectomy. For the entire sample, there were no significant declines in intelligence quotient (IQ) following surgery. Children who underwent left temporal lobectomy demonstrated no significant loss in verbal intellectual functioning and improved significantly in nonverbal intellectual functioning. Children who underwent right temporal lobectomy did not demonstrate significant changes in intellectual functioning. Although group scores showed no change in overall IQ values, an analysis of individual changes revealed that approximately 10% of the sample experienced a significant decline and 9% experienced significant improvement in verbal functioning. Significant improvement in nonverbal cognitive function was observed in 16% of the sample and only 2% of the sample showed significant declines. Risk factors for significant decline included older patient age at the time of surgery and the presence of a structural lesion other than mesial temporal sclerosis on MR imaging. CONCLUSIONS: The present study provides preliminary data for establishing the risk of cognitive morbidity posed by temporal lobectomy performed during childhood. With respect to global intellectual functioning, a slight improvement was significantly more likely to occur than a decline. However, there were several patients in whom significant declines did occur. It will be necessary to study further the factors associated with such declines. In addition, further study of more specific cognitive functions, particularly memory, is needed.

Effects of anomalous language representation on neuropsychological performance in temporal lobe epilepsy.

OBJECTIVE: To examine the effects of anomalous language representation (i.e., mixed- and right-cerebral dominant) on neuropsychological performance. BACKGROUND: Right cerebral language dominance resulting from early cerebral injury is associated with relatively preserved language function with decreased visuospatial ability. However, previous reports of this phenomenon have examined patients with relatively large cerebral injuries (e.g., infantile hemiplegia) or limited sample sizes. METHODS: A total of 561 patients with complex partial seizures of left temporal lobe origin were studied. Patients were classified into left (n = 455), bilateral (n = 58), and right (n = 48) language dominant groups based on Wada testing. RESULTS: Right language dominant patients performed more poorly on multiple tests of visuospatial function, including Performance IQ (PIQ), than did left language patients. No significant group differences were detected for measures of language or general verbal function. The effects of bilateral language on PIQ differed according to handedness. Lowered PIQ was present in the bilateral nondextral group but not for bilateral dextral patients, and this pattern was observed with other visuospatial measures. CONCLUSIONS: In patients with relatively small lesions restricted to the left mesial temporal lobe, a shift in language dominance to the right hemisphere is associated with decreased visuospatial functions but preserved verbal abilities. Nondextral patients with bilateral language representation also displayed decreased visuospatial performance, although dextral patients with bilateral language did not.

Visual confrontation naming following left anterior temporal lobectomy: a comparison of surgical approaches.

Change in visual confrontation naming was examined following left (speech dominant) anterior temporal lobectomy (ATL) as a function of surgical technique and patient characteristics. Two hundred seventeen patients with intractable left temporal lobe epilepsy were selected according to standard criteria across 8 centers, and combined into 4 surgical approaches to ATL: (a) tailored resections with intraoperative mapping of eloquent cortex, (b) tailored resections with extraoperative mapping, (c) standard resections with sparing of superior temporal gyrus, and (d) standard resections including excision of superior temporal gyrus. Changes in visual confrontation naming were examined with an index of reliable change derived from an independent sample of 90 nonsurgical patients with complex partial seizures. Results showed significant decline in visual confrontation naming following left ATL, regardless of surgical technique. Across surgical approaches, the risk for decline in visual confrontation naming was associated with a later age of seizure onset and more extensive resection of lateral temporal neocortex.

Does presurgical IQ predict seizure outcome after temporal lobectomy? Evidence from the Bozeman Epilepsy Consortium.

PURPOSE: Considerable debate exists concerning whether the presence of low preoperative IQ should be a contraindication for focal resective epilepsy surgery. METHODS: We examined the relationship between baseline IQ scores and seizure outcome in 1,034 temporal lobectomy cases from eight epilepsy surgery centers participating in the Bozeman Epilepsy Consortium. RESULTS: Those patients who continued to have seizures following surgery had statistically lower preoperative IQ scores than those who were seizure-free (p < 0.009), but only by 2.3 points. This small but statistically significant relationship was fairly robust; it was observed across seven of the eight centers, and indicates that the findings can be generalized. Among patients with IQ scores of < or = 75, 32.8% continued to have seizures following surgery, whereas 23.8% and 16.9% were not seizure-free when IQ scores were between 76 and 109 and > or = 110, respectively. Relative risk analyses revealed no significant increase in risk among patients with low IQ scores who had no structural lesions other than mesial temporal sclerosis. However, patients with IQ scores of < or = 75 had nearly a fourfold (390%) increase in risk for continued seizures as compared with those with higher IQ scores if structural lesions were present. CONCLUSIONS: While our results suggest that preoperative IQ scores alone are not good predictors of seizure outcome and should not be used to exclude patients as potential surgical candidates. IQ scores can be useful for counseling patients and their families concerning the relative risks of surgery.

Differential rates of age of seizure onset between sexes and between hemispheres?

In a descriptive analysis of 158 patients with temporal lobe epilepsy, Taylor (1969) reported that the age of first seizure varied systematically as a function of laterality and sex. We conducted inferential analyses of Taylor's original data which (1) provided support for his proposal of disproportionate left hemisphere vulnerability to seizure onset in early life, but (2) failed to provide evidence of sex differences in age of onset of unilateral seizures. Examination of these effects in a larger sample of 844 patients drawn from the Bozeman Epilepsy Consortium provided some additional support for findings from the inferential analysis. Specifically, the left hemisphere appeared more vulnerable to seizure onset in childhood, this increased vulnerability extending to about age 5 years. Age of onset of seizures was not different when males and females were compared. Thus, reanalysis of Taylor's original data as well as examination of data from a larger, more contemporary sample suggest that seizure onset varies as a function of laterality, but not sex.

The use of figural reproduction tests as measures of nonverbal memory in epilepsy surgery candidates.

The construct of nonverbal memory, as assessed by figural reproduction tests, has recently been questioned by a number of investigators. The purpose of this study was to reexamine this construct and its relationship to right temporal lobe dysfunction. Figural reproduction test scores were examined in 757 epilepsy surgery candidates obtained from 8 epilepsy centers participating in the Bozeman Epilepsy Consortium. All participants exhibited unequivocal evidence of left (LTL) or right (RTL) temporal lobe epilepsy observed in ictal and interictal EEG recordings. All subjects also had IQ scores exceeding 70, right-hand preference, and left hemisphere language dominance confirmed by intracarotid sodium amytal testing. Comparisons of LTL and RTL groups showed no significant differences in scores on the Visual Reproduction subtests from the Wechsler Memory Scale (WMS) or Wechsler Memory Scale-Revised (WMS-R) or on the copy and delayed recall conditions of the Rey-Osterrieth Complex Figure Test (ROCFT). Significant differences were observed among centers on WMS and ROCFT scores, which are likely to be a result of variations in administration and/or scoring procedures. The lack of significant differences between LTL and RTL groups in this large sample raise questions about the nature of nonverbal memory and its relationship to right temporal lobe dysfunction.

Resection of frontal encephalomalacias for intractable epilepsy: outcome and prognostic factors.

PURPOSE: Because focal encephalomalacia is an important cause of medically intractable partial epilepsy and few studies have evaluated the efficacy and the safety of resecting focal-encephalomalacias to improve seizure control, we studied a cohort of 17 consecutive patients who underwent resection of encephalomalacias in the frontal lobes as a treatment of their intractable epilepsy. METHODS: We evaluated several factors for their value in predicting postsurgical seizure control. Pre- and postsurgical magnetic resonance imaging (MRI) scans were reviewed independently by 2 blinded investigators. RESULTS: At a median of 3 years of follow-up (range 0.6-7.5 years), 12 patients (70%) were seizure-free or had only rare seizures. The presence of a focal fast frequency discharge (focal ictal beta pattern) at the beginning of seizures on scalp EEG was predictive of seizure-free outcome (p = 0.017), even among patients who had complete resection of their encephalomalacias (p = 0.016). There was no significant differences in outcome with regard to age at the time of the injury that caused encephalomalacia, interval between injury and onset of seizures, duration of presurgical seizure history, presurgical seizure frequency, age at surgery, or the completeness of encephalomalacia resection. The analysis regarding completeness of encephalomalacia resection almost reached significance, suggesting that it may also be an important predictive factor (p = 0.051). CONCLUSIONS: We conclude that surgery is a very effective treatment for intractable frontal lobe epilepsy (FLE) secondary to encephalomalacias. Patients are more likely to become seizure-free if they have a focal ictal beta discharge on their scalp EEG. Complete resection of the encephalomalacia should be attempted, since our results suggest that this may be a favorable predictive factor. Moreover, the operative strategy for our patients entailed, whenever possible, complete resection of the encephalomalacias and of the adjacent electrophysiologically abnormal tissues.

Factors associated with work outcome after anterior temporal lobectomy for intractable epilepsy.

PURPOSE: Whereas the effect of anterior temporal lobectomy on seizure frequency is well recognized, less is known about its impact on work status. METHODS: One hundred thirty-four of 190 consecutive patients with temporal lobectomy participated in this study. Eligibility criteria were developed to ensure that only patients with the potential of achieving specific outcomes were included in the corresponding analyses. RESULTS: After surgery, significantly more patients were independent in activities of daily living (p < 0.001) or able to drive (p < 0.001). Income from work also increased (p < 0.01). Nearly one fifth of the patients who were eligible for analysis had either a gain (8%) or a loss (11%) of full- or of part-time work. Univariate analyses revealed the following factors to be associated with full-time work after surgery: student or full-time work within a year before surgery, full-time work experience before surgery, full- or part-time employment experience before surgery, no disability benefits before surgery, low postsurgical seizure frequency, improved postsurgical seizure control, excellent postsurgical seizure control, driving after surgery, and further education after surgery (p < 0.05). Significant factors on multivariate analysis were being a student or having full-time work within a year before surgery [odds ratio, 16.2 (95% CI, 4.3-60.5)], driving after surgery [15.2 (3.2-72.0)], and obtaining further education after surgery [9.2 (2.2-53.0)]. CONCLUSIONS: Anterior temporal lobectomy for intractable epilepsy improves activities of daily living and the ability to drive. Work outcome of this surgery is influenced by presurgical work experience, successful postsurgical seizure control especially to allow driving, and obtaining further education after surgery.

Neuropsychologic assessment in surgical treatment of epilepsy.

Neuropsychologic assessment has long been an integral part of evaluation for surgical treatment of epilepsy. Neuropsychologic evaluation and consultation continue to be an important part of the assessment for operative intervention for epilepsy, but the role of neuropsychology has changed over time. At one time, neuropsychologic assessment assumed a diagnostic role in preoperative evaluation for epilepsy and also contributed to the lateralization and localization of the seizure focus. Sophisticated electroencephalographic techniques and especially neuroimaging have revolutionized the diagnosis and management in epilepsy surgical treatment centers. Although still helpful, neuropsychology no longer has a major role in lateralization or localization of seizure onset. This report describes neuropsychologic evaluation and its current role in surgical treatment of epilepsy. The characteristics and purposes of neuropsychologic assessment and Wada testing (intracarotid injection of amobarbital) are described. Current research on assessment of emotional adjustment and on its predictors before and after surgical therapy for epilepsy is reviewed. Finally, the risk for neuropsychologic decline after temporal lobectomy is discussed in light of recent research on preoperative memory, hippocampal pathologic lesions, and quantitative neuroimaging data.

Routine EEG and temporal lobe epilepsy: relation to long-term EEG monitoring, quantitative MRI, and operative outcome.

PURPOSE: To investigate the relation among routine EEG, long-term EEG monitoring (LTM), quantitative magnetic resonance imaging (MRI), and surgical outcome in temporal lobe epilepsy (TLE). METHODS: We evaluated 159 patients with intractable TLE who underwent an anterior temporal lobectomy between 1988 and 1993. The epileptogenic temporal lobe was determined by ictal LTM. A single awake-sleep outpatient EEG with standard activating procedures was performed before LTM. EEGs were analyzed by a blinded investigator. RESULTS: MRI scans showed unilateral medial temporal atrophy (109 patients) or symmetrical hippocampal volumes (50 patients). The surgically excised epileptogenic brain tissue revealed mesial temporal sclerosis, gliosis, or no histopathologic alteration. Routine EEG revealed temporal lobe epileptiform discharges in 123 patients. Routine EEG findings correlated with the temporal lobe of seizure origin (p < 0.0001) and the results of MRI volumetric studies (p < 0.0001). Interictal epileptiform discharges were seen only during LTM in 24 patients. Routine EEG was disconcordant with interictal LTM in another 20 patients. MRI-identified unilateral medial temporal lobe atrophy was a strong predictor of operative success (p < 0.0001). There was no significant relation between the routine EEG findings and operative outcome (p > 0.20). CONCLUSIONS: Results of this study modified our approach in patients with TLE. Interictal epileptiform discharges localized to one temporal lobe on serial routine EEGs or during LTM may be adequate to identify the epileptogenic zone in patients with MRI-identified unilateral medial temporal lobe atrophy.

Learned helplessness, attributional style, and depression in epilepsy. Bozeman Epilepsy Surgery Consortium.

PURPOSE: We wished to examine the relevance of the theory of learned helplessness in general, and attributional style in particular, to the understanding of depression among patients with epilepsy. METHODS: Patients with lateralized temporal lobe epilepsy (TLE) (right = 73, left = 70) were administered two self-report depression inventories [Beck Depression Inventory (BDI), Center for Epidemiological Studies-Depression scale (CES-D)]. Depression scores were examined in relation to a key component of the revised theory of learned helplessness (attributional style) using the Optimism/Pessimism Scale. RESULTS: Attributional style was significantly associated with increased self-reported depression and remained significant when the effects of several confounding variables were controlled [age, age at onset, laterality of TLE, sex, and method variance]. CONCLUSIONS: The results indicate that the concept of learned helplessness in general, and attributional style in particular, are related to the genesis of depression in epilepsy. Because they are known to be related to depression in the general population, and because specific techniques for intervention and prevention are available, greater consideration of learned helplessness and attributional style in the genesis of depression in epilepsy may be worthwhile.

Bilateral magnetic resonance imaging-determined hippocampal atrophy and verbal memory before and after temporal lobectomy.

We investigated pre- and postoperative verbal memory in temporal lobectomy patients who had volumetrically symmetric hippocampi. Pre- and postoperative verbal memory data based on the Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS-R) were obtained from 15 left and 18 right temporal lobectomy patients. The difference between hippocampal volumes (R/L) was between -0.1 and 0.3 cm3, which is indeterminate for lateralizing hippocampal atrophy. Patients were divided into four groups based on side of operation and combined hippocampal volume expressed as a function of total intracranial volume (R + L volume/total intracranial volume). Patients with a combined hippocampal volume that was smaller than any combined hippocampal value of a normal control group were defined as bilaterally atrophic. Left temporal lobectomy patients demonstrated the expected decrease in verbal memory postoperatively regardless of whether the volumetrically symmetric hippocampi were nonatrophic or atrophic. Left temporal lobectomy patients with bilaterally atrophic hippocampi, however, had the poorest verbal memory before and after operation. Right temporal lobectomy patients tended to have improved verbal memory after operation whether or not the volumetrically symmetric hippocampi were atrophic. We conclude that side of operation is a more potent predictor of verbal memory outcome than is hippocampal atrophy when hippocampi are bilaterally symmetric and that left temporal lobectomy patients with bilateral atrophy may be at risk for greater functional deficits after operation.

Mesial temporal sclerosis: diagnosis with fluid-attenuated inversion-recovery versus spin-echo MR imaging.

PURPOSE: To compare the accuracy of a fluid-attenuated inversion-recovery (FLAIR) sequence with that of a conventional double spin-echo (SE) sequence in the identification of increased signal intensity of the hippocampus in mesial temporal sclerosis (MTS). MATERIALS AND METHODS: Three blinded reviewers independently graded the FLAIR and SE images in 36 patients with intractable complex partial seizures. Reproducibility was tested. At histopathologic examination, the criterion standard, 32 patients had MTS. RESULTS: The accuracy of FLAIR images was 97% versus 91% for SE images (P<.02). The radiologists preferred the contrast properties of FLAIR to those of SE images by a significant margin (P<.0001). Surgical to nonsurgical hippocampal contrast-to-noise ratio (C/N) measurements were better for the second echo of the SE sequence than for FLAIR (P<.002). Hippocampus-to-background tissue C/N was superior with FLAIR (P<.0001). CONCLUSION: FLAIR provides images with T2-weighted contrast and complete suppression of high signal intensity of CSF. Incorporation of a FLAIR sequence into the routine MR evaluation of patients with epilepsy is recommended.

Intracarotid amobarbital procedure. The Wada test.

Wada testing has been a standard part of temporal lobectomy evaluation since the early 1960s. Although the procedure was initially used to lateralize language function, it was soon modified to assess risk for postoperative amnesia. The use of the procedure has now evolved to include prediction of degrees of memory decline. This use has been criticized, but more recent research has better described important parameters of the procedure and supported its validity. The Wada test is effective in lateralizing seizure onset, predicting postoperative seizure control, and predicting degree of verbal memory decline following left temporal lobectomy. The validity of Wada test data has also been supported by correlations between Wada memory performance and hippocampal pyramidal cell loss or MR imaging determined hippocampal volumes. It remains to be seen, however, if Wada memory performance and data from other sources such as MR imaging, ictal SPECT, positron emission tomography, or functional MR imaging are redundant or independently contribute to patient diagnosis and management.

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.

Electrocorticography and temporal lobe epilepsy: relationship to quantitative MRI and operative outcome.

We investigated the relationship between electrocorticography (ECoG), quantitative magnetic resonance imaging (MRI), and surgical outcome in 165 patients with intractable nonlesional temporal lobe epilepsy (NLTLE). A standard mesial temporal resection was performed in all patients. Patients with an operative follow-up < 1 year were excluded from the study. The extent of the lateral temporal neocortex resection (LCR) was guided by ECoG and the side of surgery. The extent of the LCR was not predictive of seizure outcome in patients with or without hippocampal formation atrophy (p > 0.5). Patients undergoing a right anterior temporal lobectomy had a larger LCR (p < 0.0001), but the side of surgery was not of predictive value in determining seizure outcome (p > 0.1). The topography of the acute intracranial spikes did not correlate with operative outcome (p > 0.5) and was independent of hippocampal volumetric studies (p > 0.5). The postexcision ECoG was also shown not to be of prognostic importance (p > 0.5). Our results indicates that the extent of the lateral temporal cortical resection and the ECoG findings are not important determinants of surgical outcome in patients with NLTLE.