Periventricular nodular heterotopia: epileptogenic findings

PURPOSE: We studied 17 patients with periventricular nodular heterotopia (PNH) to further investigate the electroclinical pictures and semiology of the associated seizures. METHODS: PNH was diagnosed by means of magnetic resonance imaging (MRI). The patients' clinical and familial histories were carefully analyzed, and their electroclinical features and course of epilepsy followed for periods ranging from 10 months to 22 years. The electroclinical data were compared with those of previously reported PNH cases. RESULTS: The patients were subdivided into those with bilateral (7) and unilateral (10) PNH. The former were mainly characterized by structural abnormalities in the posterior cerebral fossa and multiple seizure types; the latter were characterized by the paratrigonal location of the malformation and, frequently, by elementary seizures with a visual or auditory onset. Focal seizures were drug resistant in most cases. The interictal EEG abnormalities were always focal and consistent with the location of the PNH. A previously unreported photic driving of posterior background activity was observed in all patients and was always consistent with the PNH location. CONCLUSIONS: Our present findings and previously reported data show that bilateral and unilateral PNH cases are different in their morphological and electroclinical features and may be determined by different etiologies. The female predominance, frequent familial occurrence, and positive family history for epilepsy suggest that genetic factors may be involved in the genesis of bilateral and symmetrical PNH, whereas the presence of prenatal risk factors and its location in the watershed paratrigonal area suggest that vascular mechanisms may determine unilateral PNH.     

Amygdala atrophy and seizure outcome after temporal lobe epilepsy surgery

Surgical outcome in hippocampal atrophy (n = 44) and amygdalohippocampal atrophy (n = 14) were compared. Hippocampal atrophy had better seizure-free outcome than amygdalohippocampal atrophy (80% versus 50%, p = 0.043). Severity of hippocampal atrophy correlated with duration of epilepsy in patients with hippocampal atrophy (r = 0.4, p = 0.007), but not in those with amygdalohippocampal atrophy, suggesting that these two groups may have a different pathogenesis.     

Olfactory functioning before and after temporal lobe resection for intractable seizures.

An olfactory test battery was administered monorhinically to 21 epilepsy patients prior to and 6 mo after unilateral medial temporal lobe resection for treatment of intractable seizures. 33 matched control Ss were also tested. Presurgically, controls and patients exhibited normal sensitivity for 1-butanol. Patients performed at levels significantly below controls on tests for odor discrimination, odor memory, and odor naming. Left-resected patients did not show significant changes following surgery. Right-resected patients demonstrated significant right nostril decline. Postsurgical changes demonstrated by the right-resected group were not attributable to deficits in primary sensory function or to deficits in cognition brought on by surgery. These findings imply that right medial temporal lobe structures play a greater role in olfactory processing than do corresponding structures in the left hemisphere. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Outcome after temporal lobectomy in bilateral temporal lobe epilepsy

We determined how noninvasive presurgical data relate to prognosis after temporal lobectomy in patients with independent bilateral temporal lobe (IBTL) complex partial seizures on the intracranial electroencephalogram (EEG). Between 1986 and 1994, 28 patients had IBTL seizures on intracranial EEG. Fifteen of these 28 patients underwent temporal lobectomy and 13 were not offered surgery. Of the 15 patients who had surgery, 10 patients became seizure-free. Magnetic resonance imaging (MRI) and the Wada test were the only variables associated with a seizure-free outcome. Seven of 10 seizure-free patients had a lateralized Wada result or the presence of unilateral hippocampal sclerosis, whereas none of the patients with persistent seizures had either of these findings. Variables not found to be predictive of a seizure-free outcome included location of scalp interictal spikes, degree of seizure-onset laterality, presence of early epilepsy risk factor, duration of epilepsy, and full-scale intelligence quotient. We conclude that MRI and the Wada test provide information of prognostic value in patients with bilateral temporal seizures independent of intracranial EEG data.     

Relationship between anatomic lesions of the temporal lobe and temporal lobe epilepsy

A structural lesion of the brain is a frequent finding in intractable partial epileptic patients. We analyse anatomo-electro-clinical characteristics of 58 patients in which MR showed a lesion inside the temporal lobe. They are 29 males and 29 females with a mean age at surgery of 23.5 +/- 10.7 years (2.6-45.9). The mean epilepsy duration is of 13.4 +/- 8 years (1.3-35.5), with a mean seizure frequency of 28.7 +/- 43.6 per month, with a great inter-individual variability (from 3 per month to 15 a day). The minimum follow-up is 3.5 years. A video-EEG monitoring was performed in 21 cases, while a stereo-EEG investigation was judged mandatory in 26. On the basis of anatomo-electro-clinical correlations and of the results of presurgical investigations, the epileptogenic area was proved to be temporal in 49 cases, temporal but controlateral to the lesion in 1, and at least bilobar in 8 patients.     

Stereotaxic surgery of temporal lobe epilepsy

Forty patients with temporal epilepsy were operated on with a stereotaxic technique. Eleven patients had a unilateral localization of the epileptic focus, and in 29 bitemporal foci were diagnosed. In evaluating the results of the treatment the dynamics of the epileptic fits, the peculiarities of changes in the mental status, and the degree of social adaptation were taken into consideration. A postoperative improvement was achieved in 73% of the patients with monotemporal lesions, while in those with bitemporal epilepsy and distinct persistent mental disorders the state was improved in 44% of the cases. Indications for the choice of the zone of destruction depending on the clinical peculiarities of the lesion are presented.     

A case of intractable temporal lobe epilepsy: discrepancy between epileptogenic area and structural lesion demonstrated by subdural recording

We reported a 25-year-old man with intractable right temporal lobe epilepsy in whom subdural recording successfully delineated the epileptogenic area in the right anterior mesial to basal temporal region in spite of the presence of a postoperative lesion in the right posterior temporal region. The patient underwent right posterior temporal resection due to ependymoma at the age of 8 years. Since age 19, he had suffered from medically intractable psychomotor seizures. Ictal scalp-recorded EEG suggested an epileptogenic area at the right temporal area, but it could not specifically demarcate the site because of bone deficits from the previous surgery. Ictal SPECT showed a hyperactive area in the right anterior temporal area, which was inconsistent with the MRI finding. In case of partial epilepsy associated with structural lesion like in the present case, if results of various non-invasive studies are discrepant as to the epileptogenic area, invasive studies using, for example, subdural EEG monitoring is necessary to determine the responsible area.     

Modified approach for the selective treatment of temporal lobe epilepsy: transsylvian-transcisternal mesial en bloc resection

1. Intracerebronventricular (i.c.v.) injection of gamma-mangostin (10-40 nmol/mouse), a major compound of the fruit hull of Garcinia mangostana Lin., like ketanserin (10, 20 nmol/mouse, i.c.v.) inhibited 5-fluoro-alpha-methyltryptamine (5-FMT) (45 mg kg(-1), i.p.)-induced head-twitch response in mice in the presence or absence of citalopram (a 5-hydroxytryptamine (5-HT)-uptake inhibitor). 2. Neither the 5-FMT- nor the 8-hydroxy-2-(di-n-propylamino)tetralin (5-HT1A-agonist)-induced 5-HT syndrome (head weaving and hindlimb abduction) was affected by gamma-mangostin or ketanserin. 3. The locomotor activity stimulated by 5-FMT through the activation of alpha1-adrenoceptors did not alter in the presence of gamma-mangostin. 4. 5-HT-induced inositol phosphates accumulation in mouse brain slices was abolished by ketanserin. Gamma-mangostin caused a concentration-dependent inhibition of the inositol phosphates accumulation. 5. Gamma-mangostin caused a concentration-dependent inhibition of the binding of [3H]-spiperone, a specific 5-HT2A receptor antagonist, to mouse brain membranes. 6. Kinetic analysis of the [3H]-spiperone binding revealed that gamma-mangostin increased the Kd value without affecting the Bmax value, indicating the mode of the competitive nature of the inhibition by gamma-mangostin. 7. These results suggest that gamma-mangostin inhibits 5-FMT-induced head-twitch response in mice by blocking 5-HT2A receptors not by blocking the release of 5-HT from the central neurone. Gamma-mangostin is a promising 5-HT2A receptor antagonist in the central nervous system.     

Familial temporal lobe epilepsy: a clinically heterogeneous syndrome

We describe the clinical characteristics of a group of patients with familial temporal lobe epilepsy (TLE) in 11 kindreds with 36 affected individuals identified and investigated at the Montreal Neurological Hospital. Seizure types were simple partial (n = 20), complex partial (n = 29), and rare generalized tonic-clonic. Simple and complex partial seizures were infrequent or well controlled by anticonvulsant medication in 17 of 29 patients (59%) and without optimal response to medical therapy in 12 of 29 patients (41%). Pedigree analysis suggested autosomal dominant inheritance with incomplete penetrance. The syndrome of familial TLE has heterogeneous clinical manifestations and is not always benign.     

Neuropsychological outcome following anterior temporal lobectomy in patients with and without the syndrome of mesial temporal lobe epilepsy.

The nature, pattern, and degree of neuropsychological change following anterior temporal lobectomy (ATL) were examined as a function of the presence or absence of the syndrome of mesial temporal lobe epilepsy (MTLE). Fifty-four patients exhibited the syndrome of MTLE, while 34 patients were without the syndrome (non-MTLE). The test-retest performance of a group of 40 epilepsy patients who did not undergo surgery was used to derive regression based estimates of test-retest change. Overall, the MTLE group did not show significant cognitive decline following ATL. In contrast, the left non-MTLE group showed significant declines on verbal memory, confrontation naming, and verbal conceptual ability. Further, verbal memory was the most substantial area of decline, and was independent of seizure outcome. Clinical and theoretical implications of these findings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anterior temporal abnormality in temporal lobe epilepsy: a quantitative MRI and histopathologic study

OBJECTIVE: To examine the nature and frequency of anterior temporal lobe (AT) abnormalities that occur in intractable temporal lobe epilepsy (TLE). METHODS: We reviewed the MR scans and clinical histories of 50 consecutive patients with intractable TLE. Histopathology was available in 42 surgically treated cases. RESULTS: MRI demonstrated loss of the gray-white matter differentiation and decreased T1- and increased T2-weighted signal in the ipsilateral AT in 58% of the 50 patients. This appearance was observed in 64% of the 36 patients with hippocampal sclerosis (HS) but was also seen in patients without HS. These changes were associated with temporal lobe atrophy, a higher hippocampal T2 relaxation time, and a history of febrile convulsions. Pathologic examination showed that the MRI appearances were not caused by dysplasia, degenerative abnormalities, or inflammatory change. Histologic quantitation showed increased glial cell nuclei counts in the intractable TLE cases compared with controls. There was no difference in glial cell numbers between cases with AT abnormality and those without this appearance. Presence or absence of changes was not predictive of preoperative neuropsychology, postoperative change in neuropsychology, or seizure outcome after surgery. CONCLUSIONS: These frequently seen ipsilateral changes are not caused by gliosis and may reflect a nonspecific increase in water content in the temporal lobe. This may be due to myelin abnormalities or some other as yet unidentified pathologic factor.     

Microdysgenesis in mesial temporal lobe epilepsy: a clinicopathological study

The interrelationship of mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis, and febrile convulsions still remains an enigma. Additional microscopical cortical dysplasia or microdysgenesis has been suggested as pre-existent susceptibility factor rendering the affected brain vulnerable to the development of MTLE after initial precipitating injuries such as febrile convulsions. Twenty-four MTLE cases with histopathologically definite hippocampal sclerosis were examined for clearly defined features of microdysgenesis and further signs of neocortical dysplasia. Although unequivocal signs of dysplasia were absent, 29.2% of cases showed cortical neuronal clustering, 25.0% showed perivascular clustering, and 20.8% showed increased white matter neurons. The features of microdysgenesis studied here were not linked with each other and were not related to initial precipitating injuries, positive family history, or any other clinical parameter. Their suggested fundamental role as dysplastic factor within development of hippocampal sclerosis and MTLE is not confirmed.     

Long-term follow-up after temporal lobe resection for lesions associated with chronic seizures

A follow-up study was conducted on 60 patients who had standard en bloc anterior temporal lobe resection, including mesiotemporal structures, as treatment for temporal lobe lesions associated with chronic, medically intractable seizures. Lesions were identified as glial tumors, hamartomas, or vascular malformations. Long-term outcome was assessed in terms of seizure frequency and certain psychosocial sequelae. Seizure onset occurred at an average age of 15 years (median = 13.5 years), and patients experienced seizures for an average of 13 years prior to surgery. The mean time of follow-up was 8.4 years postsurgery (median = 6 years). The Kaplan-Meier curve at median follow-up showed a seizure-free rate of 80%. Late seizure recurrence was documented for three patients; two had been seizure-free for 10 years and one for 15 years after surgery, before re-onset of seizures in the absence of tumor recurrence. A prolonged history of seizures prior to surgery was associated with a poorer seizure outcome (p = 0.06), suggesting that secondary epileptogenesis at sites distant to the lesion may develop with years of uncontrolled seizures. There was a low tumor recurrence rate of 3.3% (two cases). The psychosocial outcome was generally good, with 67% working or engaged in educational studies, and improvement noted in 59% of cases for one or more of the psychosocial factors investigated. This study confirms that anterior temporal lobe resection for temporal lesions associated with chronic seizures is a successful treatment with a high seizure-free rate following surgery and good psychosocial outcome.     

Cortical and hippocampal volume deficits in temporal lobe epilepsy

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

Amygdala damage in experimental and human temporal lobe epilepsy

The amygdala complex is one component of the temporal lobe that may be damaged unilaterally or bilaterally in children and adults with temporal lobe epilepsy (TLE) or following status epilepticus. Most MR (magnetic resonance) imaging studies of epileptic patients have shown that volume reduction of the amygdala ranges from 10-30%. In the human amygdala, neuronal loss and gliosis have been reported in the lateral and basal nuclei. Studies in rats have more specifically identified the amygdaloid regions that are sensitive to status epilepticus-induced neuronal damage. These areas include the medial division of the lateral nucleus, the parvicellular division of the basal nucleus, the accessory basal nucleus, the posterior cortical nucleus, and portions of the anterior cortical and medial nuclei. Otherwise, other amygdala nuclei, such as the magnocellular and intermediate divisions of the basal nucleus and the central nucleus, remain relatively well preserved. Amygdala kindling studies in rats have shown that the density of a subpopulation of GABAergic inhibitory neurons that also contain somatostatin may be reduced even after a low number of generalized seizures. While analyses of histological sections and MR images indicate that in approximately 10% of TLE patients, seizure-induced damage is isolated to the amygdala, more often amygdala damage is combined with damage to the hippocampus and/or other brain areas. Moreover, recent data from rodents and nonhuman primates suggest that structural and functional alterations caused by seizure activity originating in the amygdala are not limited to the amygdala itself, but may also affect other temporal lobe structures. The information gathered so far on damage to the amygdala in epilepsy or after status epilepticus suggests that local alterations in inhibitory circuitries may contribute to a lowered seizure threshold and greater excitability within the amygdala. Furthermore, damage to select nuclei in the amygdala may predict impairment of performance in behavioral tasks that depend on the integrity of the amygdaloid circuits.     

Memory and intelligence in lateralized temporal lobe epilepsy and schizophrenia

The relation between use of sunscreens, different host factors and malignant melanoma was investigated in a population-based, matched case-control study of malignant melanoma in the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, between 1 July 1988 and 30 June 1990. In total, 400 melanoma patients and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire regarding different epidemiologic variables, including questions on use of sunscreens and different constitutional factors. The use of sunscreens was not found to protect against developing malignant melanoma. Instead, an unexpected relation between the use of sunscreens and the risk of developing malignant melanoma was seen (odds ratio (OR) 1.8 for almost always vs never using sunscreens). A tentative dose-response relation was found. Virtually the same ORs were seen in both sexes. Furthermore, persons younger than 50 years had a higher OR than persons older than 50 years. When different melanoma presentation sites were considered, lesions of the trunk were associated with sunscreen use in females (adjusted OR = 3.7 for almost always vs never using sunscreens), while lesions of the extremity or head and neck were associated with sunscreen use in males (adjusted OR = 3.2 for almost always vs never using sunscreens). Raised naevi on the left arm and freckling were shown to be the major constitutional risk factors (OR = 3.9 for more than three naevi vs none and OR = 1.4, respectively). The results were essentially unaltered in a histopathologically re-examined material. Further investigations are needed in order to form a basis for melanoma prevention.     

Evidence for nodular epileptogenicity and gender differences in periventricular nodular heterotopia

The new synthetic oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a potent, multifunctional molecule. It induces monocytic differentiation of human myeloid leukemia cells and adipogenic differentiation of mouse 3T3-L1 fibroblasts and enhances the neuronal differentiation of rat PC12 pheochromocytoma cells caused by nerve growth factor. CDDO inhibits proliferation of many human tumor cell lines, including those derived from estrogen receptor-positive and -negative breast carcinomas, myeloid leukemias, and several carcinomas bearing a Smad4 mutation. Furthermore, it suppresses the abilities of various inflammatory cytokines, such as IFN-gamma, interleukin-1, and tumor necrosis factor-alpha, to induce de novo formation of the enzymes inducible nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse peritoneal macrophages, rat brain microglia, and human colon fibroblasts. CDDO will also protect rat brain hippocampal neurons from cell death induced by beta-amyloid. The above activities have been found at concentrations ranging from 10(-6) to 10(-9) M in cell culture, and these results suggest that CDDO needs further study in vivo, for either chemoprevention or chemotherapy of malignancy as well as for neuroprotection.