Lateralizing value of memory tests in drug-resistant temporal lobe epilepsy

Our aim was to test the lateralizing value of a neuropsychological battery including several memory tests on a large sample of consecutive patients with drug-resistant temporal lobe epilepsy (TLE) evaluated for epilepsy surgery. We studied 73 right-handed patients (56% males, mean age 35.3 +/- 11.2 years, 49% left TLE) aged 16 years or older with normal IQ who underwent a preoperative neuropsychological assessment including several memory tests and were seizure-free after at least 1 year of follow-up. Forty-seven had TLE due to hippocampal sclerosis, whilst 26 had TLE secondary to tumors or other lesions. Receiver Operating Characteristic (ROC) analysis and discriminant function analysis were used to evaluate the lateralization value of selected tests and of the battery as a whole, respectively. In patients with TLE secondary to tumors or other lesions, no test showed significant lateralizing value. In patients with TLE due to hippocampal sclerosis, the immediate (P < 0.01) and delayed (P < 0.001) Rey Auditory Verbal Learning Test (RAVLT) displayed substantial discriminatory ability. The battery as a whole correctly classified 82% of patients with respect to side of epileptogenesis. Our findings suggest that a non-invasive, relatively short and unexpensive neuropsychological battery based on memory tests may profitably complement other well-established diagnostic procedures such as video-EEG or magnetic resonance imaging (MRI), at least in patients with drug-resistant TLE due to hippocampal sclerosis.     

Ictal vocalizations occur more often in temporal lobe epilepsy with dominant (left-sided) epileptogenic zone

Objective:   To investigate the lateralization value of ictal vocalizations in temporal lobe epilepsy (TLE).
Methods:   We reviewed video-recordings of 97 patients who had undergone presurgical evaluation programs with video-EEG (electroencephalography)–recorded complex partial seizures (CPS) and high-resolution magnetic resonance imaging (MRI). All patients had surgery due to TLE and became seizure-free. In 57 patients, determination of speech dominance was necessary by using Wada tests or functional MRI (fMRI). To reevaluate the archived seizures, we reviewed one to three consecutively recorded CPS of each patient. Altogether 223 archived seizures were analyzed. Ictal vocalization was considered to be present in a particular patient if it occurred in at least one of the recorded seizures.
Results:   Ictal vocalizations occurred in 22 patients. They occurred in 37% of left-sided and in 11% of right-sided patients with TLE (p = 0.003). In patients with determined speech lateralization, ictal vocalizations occurred in 37% of the dominant and in 14% in patients with nondominant epileptogenic zone (p = 0.04). In patients with ictal vocalizations, epilepsy began at age 8.7 ± 6, whereas in the remaining patients, epilepsy started at age 14.0 ± 9 (p = 0.017). Logistic regression showed that both hemispheric dominance and age at onset were independently associated with pure ictal vocalization (PIV).
Conclusions:   Ictal vocalization is a frequent phenomenon, occurring in 23% of patients with TLE. It is more often associated with left-sided and early onset TLE. Our results may improve the lateralization of the epileptogenic zone and suggest that nonspeech vocalizations in humans are related to the dominant (left-sided) hemisphere. Our study is a further argument that there are different subtypes of TLE depending on the age at onset.     

Nonmanipulative proximal upper extremity automatisms lateralize contralaterally in temporal lobe epilepsy

Purpose : Upper extremity automatisms are considered to be an ipsilateral seizure lateralizing sign in temporal lobe epilepsy (TLE). Herein we describe different types of contralateral upper extremity automatisms (CUEAs). Methods : One hundred ninety‐three video–(electroencephalography) EEG recordings of 59 patients were reviewed. Other than two patients who refused surgery, all patients underwent standardized temporal lobectomy with favorable postoperative outcome. Fifty‐seven seizures of 21 patients were selected with CUEAs. We evaluated their electroclinical characteristics and their relation to other lateralizing motor symptoms. Results : Two types of CUEAs were observed. Nonmanipulative, proximal upper extremity automatisms were seen unilaterally and contralaterally to the operated side. These automatisms were rhythmic; repetitive; and often occurred with a circulatory component resembling waving, flaunting, circling, or stirring movements. They occurred in 29 seizures (15%) of 11 patients (19%), in most seizures in the first half of the seizure, and never postictally, in various time sequences and combined with dystonic/tonic posturing or limb immobility. Manipulative/distal type of CUEAs occurred in 11 seizures (6%) of 7 patients (12%) on the unexpected contralateral side. These CUEAs were seen in all phases of the seizures, including in the postictal state. Discussion : Nonmanipulative unilateral proximal upper extremity automatism is a reliable lateralizing sign to the contralateral hemisphere in TLE. This sign may be pathophysiologically related to dystonic/tonic posturing. Manipulative distal automatisms have less lateralizing value.     

Lateralizing seizure focus in presurgical patients with temporal lobe epilepsy: Utility of the Ruff–Light Trail Learning Test

From a neuropsychological perspective, left or right temporal lobe abnormalities underlying seizures in patients with temporal lobe epilepsy (TLE) are thought to contribute to selective deficits in verbal or nonverbal memory abilities, respectively. The Ruff–Light Trail Learning Test (RULIT) is specifically designed to detect right hemisphere dysfunction. The purpose of our study was to examine the utility of the RULIT in distinguishing between patients with right (n = 20) and patients with left (n = 32) TLE in presurgical evaluations. We identified a significant between-group difference in RULIT scores, but not in the expected direction; that is, patients with right TLE had significantly better scores than patients with left TLE. These findings indicate that the RULIT may not be an appropriate test for presurgical epilepsy evaluations. Findings are discussed within the context of results from other lateralizing neuropsychological tests.     

Ictal automatisms with preserved responsiveness in a patient with left mesial temporal lobe epilepsy

PURPOSE: To describe the possible mechanism of ictal automatisms with preserved responsiveness (APRs) in a patient with left mesial temporal lobe epilepsy, which had not been reported previously. METHODS: Ictal EEGs recorded from bilateral foramen ovale electrodes with scalp-sphenoidal electrodes were analyzed in respect to the ictal semiology. RESULTS: The patient had a right hemispheric language dominance in the dextral. Electroclinical analysis revealed that the onset of oroalimentary automatisms coincided with the involvement of the left mesial and lateral temporal structures by spreading ictal discharges. The ictal discharge spreading was limited to the ipsilateral hemisphere throughout the seizure, which explained the intact consciousness and preserved responsiveness of the patient. CONCLUSIONS: This case suggests that APRs take place in seizures originating from the nondominant temporal lobe, during which ipsilateral mesial and lateral temporal structures are diffusely involved without spreading to the contralateral side.     

Etiology and site of temporal lobe epilepsy influence postictal cytokine release

Inflammatory mechanisms are involved in the pathogenesis of epilepsy. Vice versa, immune functions are regulated by the brain. We measured postictal changes in serum levels of the immuno-modulating cytokines IL-1β, IL-6 and TNFα in patients with well-defined temporal lobe epilepsy (TLE) and determined modifying factors. Serum levels of IL-1β, IL-6 and TNFα were quantified by ELISA at baseline as well as immediately, 1 h and 24 h after a complex partial (CPS) or secondary generalized tonic–clonic seizure (GTCS) during video-EEG monitoring in 25 patients suffering from temporal epilepsy. IL-6 increased by 51% immediately after the seizure (p < 0.01) and remained elevated for 24 h. This increase lacked in patients with hippocampal sclerosis (HS; n = 16, mean increase 28%, p > 0.5, vs. 112%, p < 0.01 in patients without HS). IL-6 levels were higher after right-sided seizures as compared to left-sided seizures 24 h after the seizure (8.7 pg/mL vs. 3.4 pg/mL, p < 0.05). In patients taking valproate (VPA, n = 9), the levels of IL-1β were higher as compared to patients not treated with VPA. The results suggest a relationship between the cytokine system and characteristics of TLE such as side and pathology.     

Mitochondrial involvement in temporal lobe epilepsy

Mitochondrial dysfunction has been identified as a potential cause of epileptic seizures and therapy-resistant forms of severe epilepsy. Thus, a broad variety of mutation in mitochondrial DNA or nuclear genes leading to the impairment of mitochondrial respiratory chain or of mitochondrial ATP synthesis has been associated with epileptic phenotypes. Additionally, with a variety of different methods impaired mitochondrial function has been reported for the seizure focus of patients with temporal lobe epilepsy and Ammon's horn sclerosis and of animal models of temporal lobe epilepsy. Since mitochondrial oxidative phosphorylation provides the major source of ATP in neurons and mitochondria participate in cellular Ca²⁺ homeostasis, their dysfunction strongly affects neuronal excitability and synaptic transmission, which is proposed to be highly relevant for seizure generation. Additionally, mitochondrial dysfunction is known to trigger neuronal cell death, which is a prominent feature of therapy-resistant temporal lobe epilepsy. Therefore, mitochondria have to be considered as promising targets for neuroprotective strategies in epilepsy.     

Significance of lateralization of upper limb automatisms in temporal lobe epilepsy: A quantitative movement analysis

Purpose: To evaluate the significance of lateralization of ictal upper limb automatisms in patients with temporal lobe epilepsy (TLE). Methods: Ictal upper limb automatisms of 28 patients with temporal lobe epilepsy were quantified. Duration of automatisms in relation to total seizure duration, movement speed, extent, length, and predominant frequencies of the movements were analyzed for both upper extremities separately and compared to the lateralization of the epileptogenic temporal lobe. Results: Predominantly ipsilateral upper limb automatisms were more common (n = 19) than predominantly contralateral automatisms (n = 9). The duration of ictal ipsilateral upper limb automatisms was significantly longer than the duration of contralateral automatisms (ipsilateral automatisms: 29 of 86 s total seizure duration; contralateral automatisms: 19 of 110 s total seizure duration; p = 0.048). Patients with ipsilateral upper limb automatisms had more often exclusively unitemporal interictal epileptiform discharges (IEDs) (84.2%) than patients with contralateral automatisms (11.1%; p < 0.001). The positive predictive value (PPV) of the combination of these parameters is 84.2%. Excellent surgical seizure outcome was better in patients with ipsilateral upper limb automatisms (77.8%) compared to those with contralateral automatisms (20%) (p = 0.09). The quantitative analysis of movement extent, average speed, maximum speed, and repetition rate of ipsilateral and contralateral upper limb automatisms did not show any statistically significant difference in this patient sample. Conclusion: The lateralization of upper limb automatisms in TLE has a good lateralizing value if the lateralization of IEDs were also taken into consideration.     

Efficacy of temporal lobe surgery for epilepsy in patients with negative MRI for mesial temporal lobe sclerosis

Epilepsy surgery is a successful treatment for refractory temporal lobe epilepsy (TLE). Reports suggest fewer seizure-free outcomes for patients with TLE and who have a negative brain MRI (nMRI) for mesial temporal sclerosis. Data were collected prospectively from patients with nMRI who underwent temporal lobe surgery for TLE characterized by unilateral ictal temporal lobe seizure onset based on a scalp video electroencephalogram or invasive subdural electrode recordings. A total of 86 patients were followed for at least 24 months after surgery. Outcome was evaluated using the Engel classification. Seizure control was obtained by 55% (47/86) of patients (Class [CL]-I), 27% (23/86) showed significant improvement (CL-II) and 19% (16/86) were deemed surgical failures. Shorter duration of epilepsy, later onset of seizures, and ictal theta rhythm (5-7 Hz) were the most significant predictors of postoperative seizure control. Although hypometabolism on positron emission tomography scan and significant memory disparity (>2.5/8) were not significant prognosticators independently, cumulatively they were predictors for favorable outcome.     

Localizing and lateralizing value of behavioral change in childhood partial seizures

OBJECTIVE: To describe clinical characteristics as well as localizing and lateralizing value of behavioral change (BC) at the onset of childhood seizures. METHODS: Five hundred forty-one videotaped seizures of 109 consecutive patients < or = 12 years with partial epilepsy and postoperatively seizure-free outcome were analyzed. Behavioral change (the first clinical feature of a certain seizure with a sudden change in the child's behavior) was evaluated by two independent investigators. RESULTS: Thirty-three (30%) patients showed BC at least once during their seizures. Behavioral changes appeared in arrestive form in 19 and with affective activities in 18 children; four patients produced both kinds of BCs, separately. Arrest-type BC happened in 16 of 50 children with right- and 3 of 59 patients with left-sided seizure onset zone (p < 0.001). Affective-type BC was observed in 17 of 67 temporal lobe epilepsy patients while it happened in only 1 of 42 children with extratemporal lobe epilepsy (p = 0.001). CONCLUSIONS: Arrest-type BC lateralizes to the right hemisphere, while affective-type BC localizes to the temporal lobe in childhood partial seizures. Type of BCs can add important information to the presurgical evaluation of young children with refractory partial epilepsy.     

Depression in temporal lobe epilepsy surgery patients: an FDG-PET study

PURPOSE: Depression is common in temporal lobe epilepsy (TLE) and after temporal lobectomy, and its etiology is obscure. In nonepileptic depression (including depression associated with other neurologic disorders), a consistent PET imaging finding is frontal lobe hypometabolism. Many TLE patients have hypometabolism involving frontal regions. Thus in data available from routine clinical assessments in an epilepsy surgery unit, we tested the hypothesis that the pattern of hypometabolism, particularly in the frontal lobe, may be associated with the depression seen in patients with TLE and TLE surgery. METHODS: We studied 23 medically refractory TLE patients who underwent anterior temporal lobectomy and who had preoperative FDG-PET scanning. All patients had pre- and postoperative psychiatric assessment. By using statistical parametric mapping (SPM-99), patterns of hypometabolism were compared between patients who had a preoperative history of depression (n=9) versus those who did not (n=14) and between those in whom postoperative depression developed (n=13) versus those in whom it did not (n=10). A significant region of hypometabolism was set at p<0.001 for a cluster of >or=20 contiguous voxels. RESULTS: Patients with a history of depression at any time preoperatively showed focal hypometabolism in ipsilateral orbitofrontal cortex compared with those who did not (t=4.64; p<0.001). Patients in whom depression developed postoperatively also showed hypometabolism in the ipsilateral orbitofrontal region (t=5.10; p<0.001). CONCLUSIONS: Although this study is methodologically limited, and other explanations merit consideration, orbitofrontal cortex dysfunction, already implicated in the pathophysiology of nonepileptic depression, may also be relevant to the depression of TLE and temporal lobectomy.     

Quantitative movement analysis differentiates focal seizures characterized by automatisms

The analysis of epileptic seizures is typically performed by visual inspection, limited by interrater variation. Our aim was to differentiate seizures characterized by automatisms with an objective, quantitative movement analysis. In part 1 of this study we found parameters (extent and speed of movement of the wrist and trunk) separating seizures with predominant proximal (hyperkinetic, n=10) and distal (automotor, n=10) limb automatisms (P<0.002). For each movement parameter we used the lowest value recorded for a hyperkinetic seizure in part 1 as the cutoff parameter in part 2 on a consecutive sample of 100 motor seizures. As in part 1, the difference between hyperkinetic and non-hyperkinetic seizures was highly significant (<0.001). When all movement parameters were above the threshold, a hyperkinetic seizure was identified with a probability of 80.8%, but the probability for a non-hyperkinetic seizure to have all parameters above the threshold was only 0.02%.     

Age-dependent seizure semiology in temporal lobe epilepsy

OBJECTIVE: To examine the effects of age on different aspects of temporal lobe seizure semiology. METHODS: We performed a video analysis of 605 archived seizures from 155 consecutive patients (age 10 months to 49 years) selected by seizure freedom after temporal lobectomy. Eighty patients had hippocampal sclerosis (HS). Beside semiological seizure classification, we assessed age dependency of several axes of seizure semiology: (1) aura, (2) number of different lateralizing signs, occurrence of ictal (3) emotional signs, (4) autonomic symptoms, (5) automatisms, and (6) secondary generalization as well as (7) the ratio of motor seizure components. RESULTS: From the 155 patients, 117 reported aura, 39 had ictal emotional signs, 51 had autonomic symptoms, 130 presented automatisms, while 18 patients showed secondary generalization at least once during their seizures. Altogether 369 (median: 2/patient) different lateralizing signs were recorded. Frequency of HS (p < 0.001), ictal automatisms (p < 0.001), secondary generalization (p = 0.014), number of different lateralizing signs (p < 0.001) increased while the ratio of motor seizure component (p = 0.007) decreased by age. Auras, emotional symptoms, and autonomic signs occurred independently of patients' ages. Hippocampal sclerosis adjusted linear models revealed that the frequency of automatisms and secondarily generalized seizures as well as the number of different lateralizing signs are HS-independent significant variables. CONCLUSION: Our findings support that brain maturation significantly influences the evolution of some important aspects (motor seizures, lateralizing signs) of temporal lobe seizure semiology. Conversely, other aspects (aura, emotional, and autonomic signs) are independent of the maturation process. This is the first report investigating age dependency of epileptic seizure semiology comparing all age groups.     

Diffusion tensor analysis of temporal and extra-temporal lobe tracts in temporal lobe epilepsy

OBJECTIVE: To determine whether the major temporal lobe white matter tracts in patients with temporal lobe epilepsy manifest abnormal water diffusion properties. METHODS: Diffusion tensor MRI measurements were obtained from tractography for uncinate, arcuate, inferior longitudinal fasciculi and corticospinal tract in 13 children with left temporal lobe epilepsy and normal conventional MRI, and the data were compared to measurements in 12 age-matched normal volunteers. The relationship between tensor parameters and duration of epilepsy was also determined. RESULTS: All four tracts in the affected left hemisphere showed lower mean anisotropy, planar and linear indices, but higher spherical index in patients versus controls. Diffusion changes in the left uncinate and arcuate fasciculus correlated significantly with duration of epilepsy. Arcuate fasciculus showed a reversal of the normal left-right asymmetry. Various diffusion abnormalities were also seen in the four tracts studied in the right hemisphere. CONCLUSION: Our findings indicate abnormal water diffusion in temporal lobe and extra-temporal lobe tracts with robust changes in the direction perpendicular to the axons. Diffusion abnormalities associated with duration of epilepsy suggest progressive changes in ipsilateral uncinate and arcuate fasciculus due to chronic seizure activity. Finally, our results in arcuate fasciculus are consistent with language reorganization to the contralateral right hemisphere.     

Depression in temporal lobe epilepsy before epilepsy surgery

PURPOSE: This study examined the association of depression with laterality of epilepsy surgery in patients with temporal lobe epilepsy before standard lobectomy. METHODS: Forty-nine patients presented for EEG telemetry for localization of epilepsy and eventual temporal lobectomy. Patients underwent routine neuropsychiatric evaluation blinded for epileptic focus, including ratings on depression. Patients were grouped according to right (n = 25, M = 10/F = 15) and left (n = 24, M = 13/F = 11) temporal lobectomy. Analysis of variance included side of surgery as grouping variable and sex, general depressive, cognitive depressive, and vegetative depressive symptoms as dependent variables. Chi2 analyses included categoric variables of sex, handedness, education, neuropathologic findings, and current affective disorders. t Tests were performed on variables of age, epilepsy duration, and cognitive function. RESULTS: Right and left temporal epilepsy groups did not differ with regard to sex, handedness, age, duration of epilepsy, education, cognitive function, and neuropathology. Patients with right temporal epilepsy rated higher on general, cognitive. and vegetative depression scores. Women scored higher on general, cognitive, and vegetative depression scores. Current affective disorders were more common in the right temporal epilepsy group. CONCLUSIONS: Depression ratings and diagnoses were more prominent in patients with right temporal lobe epilepsy and in women in particular. The strength of this laterality finding lies in the selection of patients, as all underwent epilepsy surgery. The finding on gender difference partly reflects the higher incidence of depression in women and needs further exploration. The laterality finding contrasts with recent findings in epilepsy, stroke, and trauma that associate depression with left hemispheric lesions. However, our results are consistent with findings in electrically hyperactive lesions such as gelastic and dacrystic epilepsy.     

Temporal lobe volumetric cell densities in temporal lobe epilepsy

Volumetric cell densities in 13 different subfields of the temporal lobe were calculated to test various hypotheses about mesial and lateral temporal lobe sclerosis in patients with complex partial epilepsy. In patients benefitting (primary group) from anterior temporal lobectomy (ATL), sclerosis was greater (fewer cells) in anterior than in posterior hippocampus. By contrast, the patients lacking full benefit (nonprimary group) from ATL had decreased numbers of neurons equally distributed from anterior to posterior hippocampus, indicating that zones of mesial temporal cell loss are linked to zones of epileptogenicity. These data support a model of focal hippocampal epilepsy originating from zones of cell loss and synaptic reorganization that is epileptic. There were no differences in cell densities in gyrus hippocampi or in lateral temporal gyri when patients with temporal lobe epilepsy and controls were compared. Hippocampal cell densities in mesial temporal lobe were not reduced in psychomotor epileptic patients with extrahippocampal foci consisting of foreign tissue. Variables in seizure histories were not correlated with Ammon's horn cell densities, indicating that most of the sclerosis preceded the seizures, which did virtually no significant further damage to hippocampus with repeated partial or generalized seizures.     

颞叶癫(癎)影像诊断和脑电图分析

目的探讨CT和脑电图(EEG)对颞叶癫的诊断作用。方法分析使用美国GE1800型CT机及ND-82B型EEG仪监测的28例颞叶癫。结果CT检查正常6例(21.4%),异常22例(78.6%)。EEG记录间歇期样发作19例,临床发作期9例。结论CT结合EEG对颞叶癫的诊断、定位具有重要意义。     

Hypersalivation in temporal lobe epilepsy

PURPOSE: We sought to determine whether hypersalivation helps lateralize seizure onset during complex partial seizures of temporal lobe origin. Several clinical signs, which help lateralize seizure onset, have been reported in temporal lobe epilepsy (TLE). Increased salivation only occasionally has been reported as a manifestation of partial epilepsy. METHODS: Of 590 consecutive patients admitted for video-EEG monitoring, either as a part of a presurgical evaluation of medically intractable epilepsy or for diagnosis and clarification of their paroxysmal symptoms, we identified 10 patients with ictal hypersalivation as a prominent manifestation of complex partial seizures. We reviewed the clinical features, scalp-sphenoidal video-EEG monitoring, intracarotid amytal (Wada) testing, hippocampal volumetric magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (FDG-PET) scans of these patients. RESULTS: Of the 10 patients with ictal hypersalivation, seven patients had nondominant/right TLE, and three patients had dominant/left TLE. All patients had hippocampal atrophy on volumetric MRI. Eight of the 10 patients underwent standard temporal lobectomy with amygdalohippocampectomy (six right, two left). All of the operated-on patients had a seizure-free (Engel class I) outcome, and their increased salivation resolved. Two patients, who did not undergo surgical treatment, continue to have complex partial seizures with increased salivation. CONCLUSIONS: We conclude that increased salivation as a prominent ictal finding in complex partial seizures of temporal lobe origin is more likely to be of nondominant temporal lobe origin. Further studies with larger numbers of patients are needed to replicate this finding.     

Hyperventilation-induced ictal fear in nonlesional temporal lobe epilepsy

Hyperventilation is a traditional seizure-provoking procedure used mainly in idiopathic generalized epilepsy and with a relatively limited role in partial epilepsy. Ictal fear is a rare seizure semiology seen in temporal lobe epilepsy. It has been suggested that the amygdala and anterior hippocampus are involved in generating ictal fear. We describe a rare patient with nonlesional temporal epilepsy who, while hyperventilating during an electroencephalography recording, developed complex partial seizures presenting as ictal fear. The particular sensitivity of the anterior hippocampus (probably the amygdala) to hypocapnia might be an important factor contributing to seizures. To avoid misdiagnosing this unusual condition as a pseudo-seizure, a detailed history and seizure semiology, as well as a concurrent electroencephalography recording, are mandatory.