Language reorganization in aphasics: an electrical stimulation mapping investigation.

OBJECTIVE: The purpose of this investigation was to determine whether clinical speech deficits after brain injury are associated with functional speech reorganization. METHODS: Across an 18-year interval, 11 patients with mild-to-moderate speech deficits underwent language mapping as part of their treatment for intractable epilepsy. These "aphasics" were compared with 14 matched "control" patients with normal speech who also were undergoing epilepsy surgery. Neuroanatomic data were compared with quantitative language profiles and clinical variables. RESULTS: Cortical lesions were evident near speech areas in all aphasia cases. As expected, aphasic and control patients were distinguished by quantitative language profiles. The groups were further distinguished by the anatomic distribution of their speech sites. A significantly greater proportion of frontal speech sites was found in patients with previous brain injury, consistent with frontal site recruitment. The degree of frontal recruitment varied as a function of patient age at the time of initial brain injury; earlier injuries were associated with greater recruitment. The overall number of speech sites remained the same after injury. Significant associations were found between the number of the speech sites, naming fluency, and the lesion proximity in the temporal lobe. CONCLUSION: Language maps in aphasics demonstrated evidence for age-dependent functional recruitment in the frontal, but not temporal, lobe. The proximity of cortical lesions to temporal speech sites predicted the overall extent of temporal lobe speech representation and performance on naming fluency. These findings have implications for neurosurgical planning in patients with preoperative speech deficits.

Do patients with psychogenic nonepileptic seizures produce trustworthy findings on neuropsychological tests?

Drane et al. (2006) has recently raised the possibility that patients with psychogenic nonepileptic seizures (PNES) may make poor effort in taking neuropsychological tests in comparison with patients with epilepsy (ES). Therefore, findings previously reported with PNES patients may be in error, especially with regard to tests of mental abilities. Using the same measure of effort used by Drane et al. (2006) but with more broadly selected patients, this paper attempts to replicate their findings with new samples of ES (n = 65) and PNES (n = 32) cases. However, their findings could not be replicated, and no differences in test taking effort could be demonstrated across the groups. The highly selected samples of Drane et al. (2006) appear to be responsible for their results, and neuropsychological findings with PNES patients appear to be as trustworthy as those with ES patients.

Do recent seizures and recent changes in antiepileptic drugs impact performances on neuropsychological tests in subtle ways that might easily be missed?

PURPOSE: The possibility that a recent seizure or a recent change in antiepileptic medication might produce an occult change in neuropsychological performance is of interest, and especially so in the context of evaluation for epilepsy surgery. Such an evaluation is often done in a setting of video-EEG monitoring where a strong effort is made to produce seizures as quickly as possible with abrupt changes in medication, alterations in sleep, etc., which could impact the validity of neuropsychological findings. METHODS: A total of 126 adults were studied who had seizures of strictly temporal origin (47 right, 79 left) and whose recent medication history and seizure occurrence prior to testing was as clear as possible. All were tested with an extensive neuropsychological battery with great attention to giving tests only when the patients appeared clinically not to be suffering from recent seizures (seizures occurring on the day of testing or on the day prior to testing) or medication change effects. The cognitive correlates of side of seizures were also evaluated in order to provide a strength-of-effect comparison with recency of AED changes and seizures. RESULTS: Findings from three-way ANOVA showed a possible slight adverse effect of recent AED change, no effects of recent seizures, and a sizeable relationship with side of seizures. A simultaneous consideration of all three of these variables did not provide additional findings of interest. CONCLUSIONS: Although it is not possible to completely rule out some subtle cognitive effects of recent changes in medication or recent seizures, this investigation does not provide evidence for such effects when the neuropsychological evaluation is conducted carefully with no testing during any questionable or definite postictal periods.

Gender differences in handedness and speech lateralization related to early neurologic insults.

Left-handedness is a normal variant but also may result from early-life brain insults. Speech typically resides in the left cerebral hemisphere in normal subjects. In 170 subjects with past brain injuries, bilateral or right hemisphere speech lateralization, determined by the intracarotid amobarbital procedure, was more frequent in females (19 vs 5, p = 0.003) as was left-handedness (26 vs 10, p = 0.004). This could be attributed to greater plasticity or functional symmetry in females.

Neuropsychological effects of seizures.

The neuropsychological effects of seizures, including an accumulation of single attacks, on mental abilities are explored through a selective review of the world's literature. Each paper included in this review was longitudinal in nature, and in each case, formal psychological testing was accomplished both at the beginning and at the end of the study. Of the 22 investigations meeting all requirements for inclusion, 9 focused on children and 13 on adolescents and adults. Some difficulties were encountered in that the types and numbers of seizures occurring during the studies were rarely included. Except in three studies where there were very few seizures of any kind, it appears justifiable to assume that the patients in all other studies had active seizure disorders. Assuming this to be true, in 12 of the remaining 20 papers, a relationship was found between seizures and changes in mental abilities, in 5 cases the results were mixed or uncertain, and in 3 cases the available evidence was against such a relationship. Mild but definite relationships between seizures and mental decline are supported by this literature review, but these relationships require much more study, particularly with a clearer understanding of the types and frequencies of seizures experienced. Suggestions for future research are offered.

Assessment of CNS effects of antiepileptic drugs by using quantitative EEG measures.

PURPOSE: Antiepileptic drugs (AEDs) can be associated with adverse neurologic effects including cognitive dysfunction. Objective methods for recognizing AED effects on the brain could be valuable for long-term management. We compared quantitative EEG measures and cognitive tests in a group of patients beginning or ending AED therapy. METHODS: Subjects included 20 patients beginning AED therapy (AEDon), 12 patients stopping AED therapy (AEDoff), 33 patient controls receiving stable AED therapy (AEDco), and 73 healthy controls (Nco). All subjects underwent structured EEG recording and a cognitive test battery before change in AED dose and again 12-16 weeks later, >or=4 weeks after the last dose change. Four occipital EEG measures (peak frequency, median frequency, relative theta and delta power) were analyzed. Cognitive test changes were scored by using test-retest regression equations based on the Nco subjects. Wilcoxon tests were used for two-group comparisons. RESULTS: AEDons had a significant decrease, and AEDoffs, a significant increase in the peak frequency of the EEG rhythm, as compared with controls. Results for median frequency and theta power were similar. Change in the EEG peak frequency correlated with an aggregate cognitive change measure (r2= 0.71; p < 0.001), individual cognitive measures, and subjective complaints. Of the combined AEDon/AEDoff patients, 58% exceeded the 95% confidence interval for test-retest change in EEG peak frequency. CONCLUSIONS: Quantitative measures derived from the occipital EEG are sensitive to AEDs and correlate with AED-related cognitive effects and subjective complaints. Although this correlation does not indicate a direct relation, quantified EEG may be a practical measure of AED impact on the brain.

Identifying potential surgical candidates in patients with evidence of bitemporal epilepsy.

PURPOSE: To determine which patients with evidence of medically refractory bitemporal epilepsy are potentially good candidates for surgical therapy. METHODS: We reviewed 42 adults with intractable seizures who were found to have bitemporal ictal onsets, based on scalp video-EEG long-term monitoring (LTM). All underwent invasive LTM before surgery. Surgical outcomes were classified as seizure free, >75% reduction in seizures, or <75% reduction in seizures, >or=1 year after resection. We related the following factors to outcome: (a). >75% preponderance of interictal scalp EEG discharges to one temporal region; (b). magnetic resonance imaging (MRI) findings; (c). lateralizing deficits on verbal or visual reproduction memory testing; and (d). memory failure with injection contralateral to side of surgery on Wada testing. RESULTS: Twenty-six (62%) of 42 patients had unilateral ictal onsets based on intracranial studies. Seizure freedom (occurring in 64% of this group), or >75% seizure reduction (found in 12% of subjects) occurred only when at least one of the following three factors was concordant with the side of surgery: preponderance of interictal scalp EEG discharges, unilateral temporal lesion on MRI, or lateralizing verbal or visual reproduction memory deficits on neuropsychological tests (p = 0.004). Seven subjects with bilateral ictal onsets based on intracranial studies had resections based on preponderance of seizures to one side, or other lateralizing noninvasive abnormality. Five of these (all of whom had >or=80% of seizures originating from one side) had >75% reduction in seizures. CONCLUSIONS: Invasive monitoring to pursue possible surgical therapy for patients with surface EEG evidence of bitemporal epilepsy may be justified only when some lateralizing feature is found in other noninvasive assessments.

Factors predicting outcome of surgery for intractable epilepsy with pathologically verified mesial temporal sclerosis.

PURPOSE: To examine the subgroup of patients with medically intractable epilepsy receiving temporal lobectomies who have pathologically verified mesial temporal sclerosis (MTS) and to determine the relation of demographic and clinical factors, results of diagnostic testing, and details of the surgical procedure with prognosis for achieving control of seizures. METHODS: All patients receiving surgical treatment for intractable epilepsy between 1991 and 1998 at the University of Washington were reviewed. There were 118 patients who met inclusion criteria of adequate pathological analysis showing MTS without a progressive process and a minimum of 1-year follow-up. RESULTS: Only personal history of status epilepticus demonstrated significant (p = 0.0276) prediction of outcome, increasing the risk of surgical failure. No other factors were significant predictors of outcome, including history of febrile seizures, possible etiologic factors, EEG, magnetic resonance imaging (MRI) or neuropsychological testing results, or extent of resection. CONCLUSIONS: Many factors that have been previously described to predict favorable outcome in the overall group of patients receiving temporal lobe resections for intractable epilepsy are, in fact, predictors of MTS and lose their predictive value when the subgroup of patients with confirmed MTS is examined. Neurosurgical treatment of MTS can be very effective even in the presence of significant etiologic factors, or of bilateral or extratemporal abnormalities on EEG or MRI.

Progressive cognitive decline in adolescents and adults with epilepsy.

The effects of an accumulation of single seizures upon mental abilities in adolescents and adults is explored through a selective review of the world's literature. The papers reviewed were divided up into cross-sectional and longitudinal studies. Of 16 investigations meeting all requirements for inclusion, 12 produced results pointing to a relationship between seizures and adverse cognitive change. The cross-sectional studies produced stronger results than the longitudinal ones, no doubt because the effects of co-existing factors not related to seizure effects were included in measures of cognitive decline. The longitudinal investigations showed mild but definite relationships between seizures and mental decline. However, relationships could be found only with generalized tonic-clonic seizures and not with partial attacks. Results of an original investigation were reported which were consistent with the literature review. Suggestions for future research were offered.

Effects of gabapentin and carbamazepine on the EEG and cognition in healthy volunteers.

PURPOSE: Antiepileptic drug (AED) therapy can be associated with neurotoxic side effects including cognitive dysfunction. Objective methods for detection of neurotoxicity in individual patients would be useful. We studied the effects of gabapentin (GBP) and carbamazepine (CBZ) on neurophysiologic and cognitive/behavioral measures in healthy volunteers. METHODS: In a 12-week, randomized, double-blind, parallel-group study of CBZ and GBP in healthy volunteers, 23 subjects completed the protocol. All achieved the target dose of 1,200 mg CBZ or 3,600 mg GBP. A structured EEG for quantitative analysis and a cognitive test battery were administered before AED therapy and again after 12 weeks of therapy. Test-retest differences were compared with those of 72 untreated control subjects. RESULTS: Both CBZ and GBP significantly decreased the peak frequency of the posterior (alpha) rhythm, with CBZ exerting a greater effect. Ten CBZ and six GBP subjects exceeded the 95% confidence interval (CI) for an individual. Cognitive tests revealed AED vs. control group effects for two of seven measures (Digit Symbol, Stroop) and all subjective measures. However, few subjects exceeded the 95% CI for any objective test. Differences between CBZ and GBP were not significant. Greater EEG slowing was associated with greater subjective neurotoxicity and poorer test-retest performance on a cognitive test summary measure. CONCLUSIONS: Prolonged CBZ and GBP therapy induced EEG slowing that correlated with cognitive complaints and often exceeded the confidence interval for individual subjects. Quantitative EEG measures may be useful in the objective determination of AED-related neurotoxicity.

The experience of earthquakes by patients with epileptic and psychogenic nonepileptic seizures.

PURPOSE: We sought to understand better the experience of seizures by studying differences in the subjective experience of being in an earthquake between patients with epileptic (EP) and nonepileptic (NES) seizures. METHODS: Forty-eight patients with CCTV/EEG-documented EP or NES who were in the Seattle metropolitan area during the February 28, 2001 Nisqually earthquake were randomly selected for telephone interviews on their earthquake experiences, including whether they thought they were having a seizure during the event. RESULTS: Twenty-three percent of EP patients spontaneously volunteered that they initially thought they were having a seizure during the earthquake as compared with none of the NES individuals (p = 0.03). However, 35% of EP and 23% of NES patients thought they were having a seizure during it when asked directly (p = 0.37). The most common reasons given, regardless of seizure type, were shaking and feelings of losing control. Of those responding negatively, 100% of EP and 47% of NES patients said that movement of their environment indicated that it was not a seizure (p = 0.001). EP patients took an average of 42 s to realize that the earthquake was not a seizure compared with 105 s for the NES group (p = 0.06). The earthquake precipitated seizures in both groups (11.5% EP, 9.1% NES). CONCLUSIONS: EP patients were more likely to mistake the earthquake spontaneously for a seizure. This indicates these two experiences are similar and provides a glimpse into the subjective experience of a seizure for those who have never had one but have experienced an earthquake.

Effects of Vagal Nerve Stimulation on Cognition and Quality of Life in Epilepsy.

To evaluate the cognitive and quality-of-life (QOL) impacts of vagal nerve stimulation (VNS), 160 patients with uncontrolled partial seizures from 20 sites were enrolled in a double-blind study. Patients were randomly assigned to low (minimal) stimulation (n = 82) or high (now clinically used) stimulation (n = 78) conditions and given a group of cognitive and QOL tests before implantation and after 12-16 weeks of VNS treatment. Results showed no clear cognitive changes. However, fewer emotional and physical problems were reported by the High Group than the Low Group at the end of the study. The 32 patients who had at least 50% seizure relief showed slightly more improvement in QOL variables than those patients who did not demonstrate this degree of seizure reduction. Overall, a small number of favorable QOL but no cognitive changes were associated with levels of VNS stimulation that are now typically used clinically.

Evidence That Emotional Maladjustment Is Worse in Men Than in Women with Psychogenic Nonepileptic Seizures.

The purpose of this study is to examine the effects of gender on adjustment and cognition in patients with psychogenic nonepileptic seizures (NES) and on patients with epilepsy. We compared 57 women and 27 men, all at least 16 years old, with only NES as documented by long-term EEG-video monitor studies, to equal numbers of randomly selected women and men with only epileptic seizures. Variables examined included age, age of onset, education, scales from the MMPI, the WAIS-R, and the number of tests outside normal limits from the Neuropsychological Battery for Epilepsy. We found no significant differences in mean age, intelligence, or percentage of neuropsychological tests outside normal limits across the four groups. Women and men with NES had significantly later age of onset of attacks compared with subjects of either gender with epilepsy (26 years vs 13 years, P < 0.001) and men with NES had greater educational achievement than women with NES or patients with epilepsy (P < 0.02). However, the most important findings were seen on the MMPI. Men with NES exhibited significantly greater elevations on multiple scales (especially Hysteria, Depression, Hypochondriasis, Psychoasthenia, Schizophrenia) compared with men with epilepsy or women with either epilepsy or NES. We conclude that men with NES have significantly worse patterns of emotional adjustment, as measured by the MMPI, than women with NES or subjects of either gender with epilepsy.

Language Disturbances as Side Effects of Topiramate and Zonisamide Therapy.

Reversible side effects of two sulfa-containing antiepileptic drugs (AEDs), topiramate (TPM) and zonisamide (ZNS), are reported. These effects differ from those of other AEDs in that language impairment was the predominant cognitive complaint. Information was available for 42 patients exposed to TPM. Twenty-two (52%) complained of adverse effects; 12, specifically of deficits in language-related functions. Brief neuropsychological testing in four patients on TPM confirmed verbal deficits. These deficits could appear shortly after initiating TPM and disappear variably after drug withdrawal. Similar complaints were seen in a pilot study of ZNS monotherapy, administered in supratherapeutic doses, confirmed by neuropsychological testing. TPM and ZNS both contain a sulfa moiety, suggesting that verbal processing is especially sensitive to these sulfa-containing AEDs.