Imagining future events in patients with unilateral temporal lobe epilepsy.

OBJECTIVES: Imagining future events, which contain episodic and non-episodic details, has been found to (1) engage the temporal lobes bilaterally and (2) be impaired in patients with bilateral temporal lobe pathology. Here, we examined whether unilateral temporal lobe dysfunction also impairs the ability to generate future events. DESIGN: Prospective cross-sectional. METHODS: Twenty patients with a history of unilateral temporal lobe epilepsy [TLE; 10 left (LTLE) and 10 right (RTLE)] and 20 normal control (NC) subjects comparable on age, sex and education completed the Adapted Autobiographical Interview, which required recall of past and generation of future events and distinguished episodic (internal) from non-episodic (external) details. Participants also completed a battery of neuropsychological tests. RESULTS: Patients with unilateral TLE were significantly impaired in provision of internal details for past and future events, but not in the generation of external details. Examination of detail subcategories revealed that patients with LTLE did exhibit a significant deficit relative to patients with RTLE (and NC) with respect to the generation of perceptual details for both past and future events. Moreover, patients with LTLE generated significantly fewer place details for future events (relative to NC only). The overall number of internal details recalled by patients with LTLE was related to semantic fluency. CONCLUSIONS: Our study provides the first evidence that unilateral temporal lobe dysfunction is associated with not only impaired recall of past, but also the generation of future episodic details. Clinically, deficits in future thinking may reduce motivation and decision-making, and as such adversely impact behavioural regulation and socialization. PRACTITIONER POINTS: Patients with temporal lobe epilepsy generate less details when asked to describe past and potential future events, particularly with regard to details involving specific events, places and perceptions. These same patients are aware of their difficulties in this realm, but judge their past memories as similar in vividness and even more personally significant than the memories generated by control participants. The deficits in generation of future episodic details were particularly pronounced in patients with left temporal lobe epilepsy. Verbal semantic fluency was correlated with the ability to generate future scenarios.

Disruption of learning and long-term retention of prose passages in patients with focal epilepsy.

Recent investigations of accelerated long-term forgetting, a condition in which newly acquired memory is normal initially but decays rapidly over days or weeks, indicate that multiple factors might influence whether this phenomenon is seen in patients with epilepsy. Test-based differences such as learning condition or type of memory measure (e.g., recall vs recognition) as well as epilepsy variables (e.g., side, site, or frequency of epileptiform activity) may be important. The present study sought to characterize factors affecting learning and memory for prose passages in patients with focal epilepsy. We enrolled 21 patients with temporal lobe epilepsy, with and without hippocampal lesions, 11 patients with extratemporal epilepsy (ETE), and 29 healthy controls. Two matched passages were used to compare effects of initial learning condition (one exposure versus learning-to-criterion) on subsequent patterns of retention. Recall and recognition were tested at different delays (i.e., immediately, 30min, 24h, and 4days). Regression analyses and one-way ANOVAs indicated that having a left-hemisphere epileptic focus had a negative impact on learning, whilst presence of a hippocampal lesion (irrespective of side) was associated with deterioration in recall for intervals up to 24h postencoding. Learning condition affected patterns of memory decay in that the ETE group showed significant decline in recall between 24h and 4days only when stories were learned to criterion. In contrast with recall, no changes over time were evident in recognition memory, as patients with hippocampal lesions were impaired from 30min onward. Epilepsy variables other than side and site of epilepsy/lesion did not influence performance. In conclusion, the left hemisphere is involved in learning of prose material, and the hippocampus is involved in the consolidation of this material mainly for the first 24h. After this, cortical regions outside the hippocampus become important for recall.

Old dogs with new tricks: Detecting accelerated long-term forgetting by extending traditional measures.

Accelerated long-term forgetting (ALF) is a condition in which normal memory performance is displayed after short delays, but significant memory loss is detected when memory is tested after several days or weeks. This condition has been reported in patients with epilepsy, but there are few normative scores available for its detection in clinical practice. In the present study, we assessed 60 healthy control subjects 18-60years of age on three memory measures [Rey Auditory Verbal Learning (RAVLT), Logical Memory (LM), and Aggie Figures] at delays of 30min and 7days. With these normative values, we determined cutoff scores to look for ALF and then categorized the performance of 15 patients with focal epilepsy on the same tasks. Seven of the patients showed ALF, and, in four of these, no other memory deficits (i.e., deficits at 30min on at least one task) were detected. Of the several demographic and epilepsy factors examined, only higher estimated IQ and older age predicted ALF (and only on one task: RAVLT). The findings provide a useful set of data to be applied in the clinic and some insight into the factors that influence retention within the first week.

The relationship between neuropsychological functioning and FDG-PET hypometabolism in intractable mesial temporal lobe epilepsy.

We examined the relationship between baseline neuropsychological functioning and 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in intractable mesial temporal lobe epilepsy (MTLE). We hypothesized relationships between dominant temporal lobe hypometabolism and verbal memory and between nondominant temporal lobe hypometabolism and nonverbal memory in line with the lateralized material-specific model of memory deficits in MTLE. We also hypothesized an association between performance on frontal lobe neuropsychological tests and prefrontal hypometabolism. Thirty-two patients who had undergone temporal lobectomy for treatment of MTLE and who completed both presurgical FDG-PET and comprehensive neuropsychological investigations with widely used standardized measures were included. Age-adjusted composite measures were calculated for verbal memory, nonverbal memory, relative material-specific memory, IQ, executive function, attention/working memory, and psychomotor speed. Fluorodeoxyglucose positron emission tomography was analyzed with statistical parametric mapping (SPM) to identify hypometabolism relative to healthy controls. Pearson's correlation was used to determine the relationship between regions of hypometabolism and neuropsychological functioning. Dominant temporal lobe hypometabolism was associated with relatively inferior verbal memory, while nondominant temporal lobe hypometabolism was associated with inferior nonverbal memory. No relationship was found between performance on any frontal lobe measures and prefrontal hypometabolism. Statistical parametric mapping-quantified lateralized temporal lobe hypometabolism correlates with material-specific episodic memory impairment in MTLE. In contrast, prefrontal hypometabolism is not associated with performance on frontal lobe measures. We suggest that this is because frontal lobe neuropsychology tests may not be good measures of isolated frontal lobe functioning.

The cognitive profile of occipital lobe epilepsy and the selective association of left temporal lobe hypometabolism with verbal memory impairment.

We investigated the cognitive profile of structural occipital lobe epilepsy (OLE) and whether verbal memory impairment is selectively associated with left temporal lobe hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). Nine patients with OLE, ages 8-29 years, completed presurgical neuropsychological assessment. Composite measures were calculated for intelligence quotient (IQ), speed, attention, verbal memory, nonverbal memory, and executive functioning. In addition, the Wisconsin Card Sorting Test (WCST) was used as a specific measure of frontal lobe functioning. Presurgical FDG-PET was analyzed with statistical parametric mapping in 8 patients relative to 16 healthy volunteers. Mild impairments were evident for IQ, speed, attention, and executive functioning. Four patients demonstrated moderate or severe verbal memory impairment. Temporal lobe hypometabolism was found in seven of eight patients. Poorer verbal memory was associated with left temporal lobe hypometabolism (p = 0.002), which was stronger (p = 0.03 and p = 0.005, respectively) than the association of left temporal lobe hypometabolism with executive functioning or with performance on the WCST. OLE is associated with widespread cognitive comorbidity, suggesting cortical dysfunction beyond the occipital lobe. Verbal memory impairment is selectively associated with left temporal lobe hypometabolism in OLE, supporting a link between neuropsychological dysfunction and remote hypometabolism in focal epilepsy.

Cognitive behaviour therapy to improve mood in people with epilepsy: a randomised controlled trial.

This study compared a 9-week individualised Cognitive Behaviour Therapy (CBT) programme for people with epilepsy (PWE), with a wait-list control. Fifty-nine PWE were randomised and 45 (75%) completed post-treatment outcomes. People with lower quality of life (QoL), particularly for cognitive functioning, were more likely to drop out. Analyses based on treatment completers demonstrated significant improvements on the Neurological Depressive Disorders Inventory for Epilepsy (p = .045) and Hospital Anxiety Depression Scale-Depression subscale (p = .048). Importantly, CBT significantly reduced the likelihood of clinical depressive symptoms (p = .014) and suicidal ideation (p = .005). Improvements were not observed for anxiety, QoL or maintained overtime for depression. Results suggest that CBT was effective, however, and could be improved to increase patient retention and long-term outcomes.

Examining factors related to accelerated long-term forgetting in epilepsy using ambulatory EEG monitoring.

PURPOSE: Some patients with epilepsy demonstrate normal memory when this is tested at relatively short intervals (e.g., 30 min), but substantial loss over longer delay periods (e.g., days or weeks) when compared to healthy control subjects. This pattern of "accelerated long-term forgetting" (ALF) affects the everyday lives of patients, yet goes undetected by standard neuropsychological memory tests, and its pathophysiologic basis is poorly understood. By testing memory over a period of concurrent ambulatory electroencephalography (EEG), the current study aimed to investigate possible factors contributing to ALF. METHODS: Thirty-nine patients diagnosed with epilepsy or probable epilepsy underwent 5 days of continuous ambulatory EEG: 18 had normal EEG studies, 10 had focal epileptic discharges, 5 had generalized epileptic discharges, and 6 had one or more seizures. Fifteen matched healthy control subjects also participated, but did not undergo EEG. Subjects were taught 13-item word and design lists to criterion, and recall was tested at 30 min, 24 h, and 4 days. Subjects also completed questionnaires pertaining to everyday memory and mood. KEY FINDINGS: Group analyses (excluding patients who experienced seizures during monitoring) indicated that patients who experienced generalized discharges during the 24-h to 4-day delay intervals showed higher rates of forgetting for nonverbal information. Those with focal discharges showed ALF between 30 min and 4 days for verbal information, whereas those with normal EEGs over the 4 days recording had no evidence of ALF. Surprisingly, mood and epilepsy variables (such as duration of disease or number of anticonvulsant medications) showed no significant correlation with ALF. Although no aspect of nighttime sleep architecture was found to be related to recall after the first 24 h, daytime naps were associated with better retention. Self-report of everyday memory functioning was related to recall at longer delays, but not at 30 min. SIGNIFICANCE: The present findings indicated that ALF in epilepsy is associated with subclinical discharges rather than antiepileptic drugs (AEDs), mood or sleep disturbance. Measures of longer-term recall can reveal correlations with subjective everyday memory complaints that are not evident when recall is only tested at a standard (30 min) delay interval. These findings have the potential to improve treatment strategies for patients who complain of memory difficulties.

Rates of DSM-IV mood, anxiety disorders, and suicidality in Australian adult epilepsy outpatients: a comparison of well-controlled versus refractory epilepsy.

Despite recent research into the impact of seizure control on mood disorders in epilepsy, it is often assumed that rates of psychiatric disorders are higher in people with refractory rather than well-controlled epilepsy. We assessed the point prevalence of mood and anxiety disorders and suicide risk using the Mini International Neuropsychiatric Interview (MINI) in a consecutive sample of epilepsy outpatients from a tertiary referral center. One hundred and thirty patients, whose epilepsy was categorized as well-controlled versus drug-treatment-refractory epilepsy (69; 53% well-controlled epilepsy) were recruited. High rates of mood disorders (n = 34; 26%), anxiety disorders (n = 37; 29%) and suicide risk (n = 43; 33%) were found. However, there was no difference in rates of disorders or suicide risk for those with refractory versus well-controlled epilepsy. These results underscore the importance of assessment and management of psychopathology in all people with epilepsy, regardless of their seizure control.

Relationship between preoperative hypometabolism and surgical outcome in neocortical epilepsy surgery.

PURPOSE: Fluorine-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) hypometabolism has been used to localize the epileptogenic zone. However, glucose hypometabolism remote to the ictal focus is common and its relationship to surgical outcome has not been considered in many studies. We investigated the relationship between surgical outcome and FDG-PET hypometabolism topography in a large cohort of patients with neocortical epilepsy. METHODS: We identified all patients (n = 68) who had interictal FDG-PET between 1994 and 2004 and who underwent resective epilepsy surgery with follow up for more than 2 years. The volumes of significant FDG-PET hypometabolism involving the resected epileptic focus and its surrounding regions (perifocal hypometabolism) and those distant to and not contiguous with the perifocal hypometabolism (remote hypometabolism) were determined statistically using Statistical Parametric Mapping (voxel threshold p = 0.01, extent threshold ≥ 250 voxels, uncorrected cluster-level significance p < 0.05) and were compared with magnetic resonance imaging (MRI) and clinical and demographic variables using a multiple logistic regression model to identify independent predictors of seizure outcome. KEY FINDINGS: Remote hypometabolism was present in 39 patients. Seizure freedom was 49% (19 of 39 patients) in patients with glucose hypometabolism remote from the epileptogenic zone compared to 90% (26 of 29 patients) in patients without remote hypometabolism. In 43 patients with an MRI-identified lesion, seizure freedom was 79% (34 of 43 patients). In patients with normal MRI, cortical dysplasia was the predominant pathologic substrate. Multiple logistic regression analysis identified a larger volume of significant remote hypometabolism (p < 0.005) and absence of a MRI-localized lesion (p = 0.006) as independent predictors of continued seizures after surgery. SIGNIFICANCE: In patients with widespread glucose hypometabolism that is statistically significant when compared to controls, epilepsy surgery may not result in complete seizure freedom despite complete removal of the MRI-identified lesion. The volume of significant glucose hypometabolism remote to the ictal-onset zone may be an independent predictor of the success of epilepsy surgery.

Brain activation patterns of versive, hypermotor, and bilateral asymmetric tonic seizures.

PURPOSE: Patients who have seizure onset from different brain regions can produce seizures that appear clinically indistinguishable from one another. These clinically stereotypic manifestations reflect epileptic activation of specific networks. Several studies have shown that ictal perfusion single photon emission computed tomography (SPECT) can reveal propagated ictal activity. We hypothesize that the pattern of hyperperfusion may reflect neuronal networks that generated specific ictal symptomatology. METHODS: All patients were identified who were injected with (99m)Tc-hexamethyl-propylene-amine-oxime (HMPAO) during versive seizures (n = 5), bilateral asymmetric tonic seizures (BATS; n = 5), and hypermotor seizures (n = 7) in the presurgical epilepsy evaluation between 2001 and 2005. The SPECT ictal­interictal difference image pairs of each subgroup were compared with image pairs of 14 controls using statistical parametric mapping (SPM 2) to identify regions of significant hyperperfusion. Hyperperfused regions with corrected cluster-level significance p < 0.05 were considered significant. RESULTS: We have identified a distinct ictal perfusion pattern in each subgroup. In versive seizure subgroup, prominent hyperperfusion was present in the frontal eye field opposite to the direction of head version. In addition, there was associated caudate and crossed cerebellar hyperperfusion. The BATS subgroup showed pronounced hyperperfusion supplementary sensorimotor area ipsilateral to the epileptogenic region, bilateral basal ganglia, and contralateral cerebellar hemisphere. The hypermotor seizure subgroup demonstrated two clusters of significant hyperperfusion: one involving bilateral frontomesial regions, cingulate gyri, and caudate nuclei, and another involving ipsilateral anteromesial temporal structures, frontoorbital region, insula, and basal ganglia. DISCUSSION: We have identified distinct hyperperfusion patterns for specific ictal symptomatology. Our findings provide further insight into understanding the anatomic basis of seizure semiology.

The topography and significance of extratemporal hypometabolism in refractory mesial temporal lobe epilepsy examined by FDG-PET.

PURPOSE: This study aims to map the temporal and extratemporal 18-fluorodeoxyglucose positron emission tomography (FDG-PET)-defined hypometabolism in mesial temporal lobe epilepsy (MTLE). We hypothesize that quantitative analysis will reveal extensive extratemporal glucose hypometabolism (EH), that the EH is related to seizure propagation beyond the temporal lobe, hypometabolism restricted to one temporal lobe predicts a good outcome following surgery, and EH predicts a poor outcome. METHODS: Sixty-four patients were studied who had undergone temporal lobectomy for intractable MTLE and had at least 2 years of postoperative follow-up. Spatial preprocessing and statistical analysis on preoperative interictal FDG-PET using statistical parametric mapping (SPM 2) identified significant regions of hypometabolism compared to normal controls. The predictors of outcome were determined by univariable and multiple logistic regression analyses. RESULTS: EH was common and widespread, occurring most frequently in the ipsilateral insula and frontal lobe. The extent of EH was not significantly associated with age of onset or the duration of epilepsy. Presence of secondarily generalized tonic--clonic seizures (SGTCS) was associated with a larger extent of remote hypometabolism (RH, p < 0.005). Multiple logistic regression analysis identified the extent of RH and the age at surgery as independent predictors of seizure outcome. DISCUSSION: Our results indicate that RH in MTLE is associated with a poorer surgical outcome, especially if seen in the contralateral hemisphere. The extent of RH relates to SGTCS but not to duration of epilepsy.

Determining the relationship between sleep architecture, seizure variables and memory in patients with focal epilepsy.

Sleep has been shown to be important to memory. Both sleep and memory have been found to be abnormal in patients with epilepsy. In this study, we explored the effects that nocturnal epileptiform discharges and the presence of a hippocampal lesion have on sleep patterns and memory. Twenty-five patients with focal epilepsy who underwent a 24-hr ambulatory EEG also completed the Everyday Memory Questionnaire (EMQ). The EEG record was scored for length of time spent in the various sleep stages, time spent awake after sleep onset, and rapid eye movement (REM) latency. Of these sleep variables, only REM latency differed when the epilepsy patients were divided on the bases of either presence/absence of nocturnal discharges or presence/absence of a hippocampal lesion. In both cases, presence of the abnormality was associated with longer latency. Furthermore, longer REM latency was found to be a better predictor of EMQ score than either number of discharges or presence of a hippocampal lesion. Longer REM latency was associated with a smaller percentage of time spent in slow-wave sleep in the early part of the night and may serve as a particularly sensitive marker to disturbances in sleep architecture. (PsycINFO Database Record

Testing the importance of the Medial Temporal Lobes in human interoception: Does it matter if there is a memory component to the task?

Interoception is the ability to consciously perceive internal bodily states. Neuroimaging suggests that the insula (IC) and anterior cingulate cortex (ACC) mediate interoception, while studies involving patients/animals with brain lesions suggest the medial temporal lobe (MTL) is particularly important. One reason for these contrasting conclusions may lie in the types of interoceptive task used by these different approaches. Some tasks probably require integration of current physiological state with mnemonic information (e.g., how much one last ate), and these may be especially reliant upon MTL processing. We compared one task that probably requires integration - a water load task - with one that likely does not - a heart-rate tracking task - in two individuals with selective MTL damage (and with intact IC and ACC). A group of matched healthy individuals served as controls. The main finding was that individuals with MTL damage, relative to controls, were equally and significantly impaired on both types of interoception task. This suggests that MTL structures are involved in mediating interoception even when using a task (heart rate tracking) that does not seemingly require memory and that in neuroimaging studies activates the IC and ACC. The reasons for this apparent inconsistency with neuroimaging findings and the functional role of the MTL in interoception are discussed.

Frequency of a false positive diagnosis of epilepsy: A systematic review of observational studies.

PURPOSE: To determine the frequency of false positive diagnoses of epilepsy and to explore its imitators and consequences. METHOD: A systematic review of all published observational studies (to November 2015) was conducted to determine the proportion of false positive diagnoses of epilepsy. We included studies of people of all ages receiving a diagnosis of epilepsy. All observational study designs were included with the exception of case-reports and case series with fewer than 3 participants. RESULTS: Data were available from 27 studies (31 reports), reporting considerably varied frequencies of false positive diagnoses. The frequency of false positive diagnosis range from 2% to 71%. The data also suggest that syncope and psychogenic non-epileptic paroxysmal events were the commonest imitators of epilepsy. Misdiagnosis led to mismanagement with anti-epileptic drugs (AEDs) and affected legal driving status and employment. CONCLUSIONS: False positive diagnosis of epilepsy is common, even though there is considerable heterogeneity across studies. All potential imitators should be considered and clinicians should be cautious introducing AEDs without a definite diagnosis given the risk of side effects, and the possible impact on legal driving status and employment.

The impact of epileptiform abnormalities and hippocampal lesions on retention of recent autobiographical experiences: Adding insult to injury?

Accelerated long term forgetting (ALF), whereby information is rapidly lost over days or weeks has been noted in patients with epileptic conditions. The present study sought to determine which clinical factors underlie such consolidation failure for recent autobiographical experiences in patients with focal epilepsy. We enrolled 21 patients with temporal lobe epilepsy (TLE), with and without hippocampal lesions (TLE(+)=12; TLE(-)=9, respectively), 11 patients with extratemporal epilepsy (ETE) and 29 controls (NC). Recall and recognition were tested at different delays (i.e., 30min, 24h and 4 days). During the study interval, most of the patients underwent concurrent ambulatory EEG monitoring. Analyses of variance indicated Group×Delay interval interactions for recall. The TLE(+) group showed significant decline in recall by 24h delay. On recognition Group by Delay interval was not detected but main effect for Group revealed that the ETE group demonstrated ALF on recognition questions over the interval between 24h and 4 days. Regression analyses confirmed that a hippocampal lesion was particularly disruptive to consolidation over the first 24h, and that seizures were associated with memory decline over longer delays. Our findings show that the retention of autobiographical experiences involves multiple mechanisms, which operate over different timeframes.

Anxiety in epilepsy: a neglected disorder.

OBJECTIVE: Anxiety disorders and symptoms are highly prevalent and problematic comorbidities in people with epilepsy (PWE), yet they remain poorly understood and often go undetected. This research aimed to further our understanding about anxiety in PWE. METHODS: Study 1 assessed the effectiveness of the commonly utilised yet unvalidated measure (Hospital Anxiety Depression Scale-Anxiety subscale; HADS-A) to identify DSM-IV anxiety disorders in 147 adult epilepsy outpatients. RESULTS: This study found that although the HADS-A had reasonable specificity (75%), its poor sensitivity (61%) and inadequate area under the curve (.68) deemed it unreliable as a screener for anxiety disorders in this population. METHODS: Study 2 aimed to further our understanding of the relationship between anxiety disorders, as defined by clinical interview, and psychosocial correlates in PWE. One hundred and twenty-two participants from Study 1 completed a battery of psychosocial measures. RESULTS: Multivariate analysis revealed that the presence of an anxiety disorder was associated with unemployment, which was found to be the only independent predictor. That is, despite the fact that psychosocial factors together contributed to the variance in anxiety disorders none were revealed to be significant independent predictors. CONCLUSION: These findings add to the literature indicating that the HADS may indicate distress, but does not adequately identify people with anxiety disorders and highlights the urgent need for the development of a reliable anxiety screening measure for PWE. Further, the results suggest that anxiety disorders in PWE are likely to be multiply determined with respect to psychosocial factors and require further investigation.

Baló's concentric sclerosis and tumefactive demyelination: a shared immunopathogenesis?

Baló's concentric sclerosis (BCS) and tumefactive demyelination (TD) are considered atypical forms of multiple sclerosis (MS). Baló lesions are characterized by concentric rings corresponding to alternating bands of demyelination and relatively preserved myelin (Hu and Lucchinetti, 2009). Tumefactive lesions are pseudotumoural demyelinating lesions of >2 cm and may have an open ring-enhancing magnetic resonance imaging appearance (Hu and Lucchinetti, 2009; Lucchinetti et al., 2008; Altintas et al., 2012). We present a patient who developed limb weakness and focal seizures secondary to a lesion radiologically and histopathologically consistent with BCS who, six months later, developed a tumefactive demyelinating lesion. This is the first description of BCS and TD occurring in the same patient and is particularly notable because of the lack of any other more typical demyelinating lesions on the MRIs. The nature of BCS and TD in relation to more typical multiple sclerosis is discussed.

Interictal EEG, hippocampal atrophy, and cell densities in hippocampal sclerosis and hippocampal sclerosis associated with microscopic cortical dysplasia.

The EEG characteristics of isolated hippocampal sclerosis (HS) and HS associated with other types of temporal lobe pathology are not well defined. The pathologic substrate may be an important variable in determining seizure-free outcome. The objective of this study was to define the distribution of epileptiform discharges in patients with HS and HS associated with microscopic dysplasia, and to examine their relationship with hippocampal atrophy and cell loss. Thirty-four patients (15 women and 19 men; mean age, 30.6 +/- 11.2 years), all with good outcomes after temporal lobectomy (Engel classes I and II), were included. The characteristics studied were frequency and distribution of spikes, MRI-based hippocampal volume ratios, and quantitative hippocampal cell density in various subregions. The isolated HS group showed a trend to a higher percentage of epileptiform discharges maximal at the anterior temporal electrodes (89.87 +/- 17.0%; 79.5 +/- 28.2% in the dual-pathology group). The isolated HS group had, on average, significantly more cell loss (P < 0.001). There was a significant negative correlation between the amount of cell loss in the CA1 area and both anterior temporal spikes and hippocampal ratios (P < 0.05). Isolated HS and dual pathology show minimal differences in interictal spike distribution and frequency. More widespread spike distributions in severe isolated HS compared with patients with less cell loss is probably the result of less organized limbic circuitry.

A critical review of the different conceptual hypotheses framing human focal epilepsy.

In the attempt to understand the processes affecting human focal epilepsy, various models that have been proposed as a back drop to which current observations of the clinical manifestations and therapies in this disorder can be tested. There are three main models that are reviewed. The notion of epileptogenicity as described by Penfield and Jasper's epileptogenic zone model postulates that specific regions of cerebral cortex have varying degrees of importance in the generation of focal epilepsy. A variation of this hypothesis comprises the second model put forth by Talairach and Bancaud. In this view the notion of the epileptogenic zone is expanded to incorporate a larger regions of cerebral cortex involved in the seizure propagation. A third concept and more separate hypothesis suggests that all components of the neural network involved in focal epilepsy are equally importance in the initiation and maintenance of the seizure. The various concepts underlying these models are reviewed in this paper and data from clinical and neurophysiologic observations are discussed in the context of these models. We suggest in this paper that the data best supports the epileptogenic zone hypothesis put forth by Penfield and Jasper.

Accelerated long-term forgetting of verbal information in unilateral temporal lobe epilepsy: Is it related to structural hippocampal abnormalities and/or incomplete learning?

The factors contributing to accelerated long-term forgetting (ALF) are not yet clear. In this study, a 12-item word list was presented repeatedly to 23 patients with temporal lobe epilepsy (TLE) and 27 control participants (NC) until it was recalled completely on two consecutive trials or until 12 trials were undertaken. Compared to NCs, patients with hippocampal lesions and those who failed to learn the list showed ALF by one day post learning, but the alternative patient groups also showed ALF when tested after seven days. Overall, our findings suggest that in patients with TLE neither a preserved hippocampus nor intact learning protects against ALF.