Mark J. Cook

Frequency and characteristics of dual pathology in patients with lesional epilepsy

We studied 167 patients who had identifiable lesions and temporal or extratemporal partial epilepsy. Pathology included neuronal migration disorders (NMDs) (48), low-grade tumors (521, vascular malformations (34), porencephalic cysts (16), and gliotic lesions as a result of cerebral insults early in life (17). MRI volumetric studies using thin (1.5-or 3-mm) coronal images were performed in all patients and in 44 age-matched normal controls. An atrophic hippocampal formation (HF), indicating dual pathology, was present in 25 patients (15%). Abnormal HF volumes were present in those with lesions involving temporal (17%) but also extratemporal (14%) areas. Age at onset and duration of epilepsy did not influence the presence of HF atrophy. However, febrile seizures in early childhood were more frequently, although not exclusively, found in patients with hippocampal atrophy. The frequency of hippocampal atrophy in our patients with low-grade tumors (2%) and vascular lesions (9%) was low. Dual pathology was far more common in patients with NMDs (25%), porencephalic cysts (31%), and reactive gliosis (23.5%). Some structural lesions, such as NMDs, are more likely to be associated with hippocampal atrophy, independent of the distance of the lesion from the HF. In other types of lesions, such as vascular malformations, dual pathology was found when the lesion was close to the HF. A common pathogenic mechanism during pre- or perinatal development may explain the occurrence of concomitant mesial temporal sclerosis and other structural lesions because of either (1) associated developmental abnormalities or (2) predisposition to prolonged febrile convulsions. Further clarification of this issue would improve our understanding of the pathogenesis of mesial temporal sclerosis and lead to more efficient planning of surgical treatment for lesional epilepsy.

Association of hippocampal sclerosis with cortical dysgenesis in patients with epilepsy

The possible dual occurrence of hippocampal sclerosis (HS) and other structural lesions (especially cortical dysgenesis [CD]) is well established in patients with chronic partial epilepsy. We describe the frequency of additional CD in a series of 100 patients with evidence of HS, using volumetric MRI. Additional, often subtle, CD was present in 15 patients: subependymal heterotopia (six), forme fruste of tuberous sclerosis (two), focal macrogyria (two), focal cortical dysplasia (one), laminar heterotopia (one), bilateral schizencephaly (one), and simplified gyral patterns (two). In contrast, in 46 healthy volunteers, only one had possible CD (p < 0.05). Only 2 of 15 patients had a history of childhood febrile convulsions. HS is a heterogeneous condition; patients being evaluated for temporal lobe surgery should be carefully screened for additional CD using appropriate MR techniques.

EEG source localization in focal epilepsy: Where are we now?

Electroencephalographic source localization (ESL) by noninvasive means is an area of renewed interest in clinical epileptology. This has been driven by innovations in the computer‐assisted modeling of dipolar and distributed sources for the investigation of focal epilepsy; a process fueled by the ever‐increasing computational power available to researchers for the analysis of scalp EEG recordings. However, demonstration of the validity and clinical utility of these mathematically derived source modeling techniques has struggled to keep pace. This review evaluates the current clinical “fitness’ of ESL as applied to the focal epilepsies by examining some of the key studies performed in the field, with emphasis given to clinical work published in the last five years. In doing so, we discuss why ESL techniques have not made an impact on routine epilepsy practice, underlining some of the current problems and controversies in the field. We conclude by examining where ESL currently sits alongside magnetoencephalography and combined EEG‐functional magnetic resonance imaging in the investigation of focal epilepsy.

Hippocampal sclerosis in epilepsy and childhood febrile seizures

The connection between hippocampal sclerosis and childhood febrile seizures (CFS) is a contentious issue in the study of epilepsy. We investigated 107 patients with drug-resistant epilepsy by high-resolution volumetric magnetic resonance imaging (MRI). 20 had a history of CFS, 45 had focal (26) or diffuse (19) hippocampal volume loss (HVL). The frequency of CFS was significantly (p < 0.001) higher in the patients with HVL, especially of the diffuse pattern, compared to other epileptic patients without HVL and to the general population. Furthermore, the severity of HVL was greatest in those with a history of CFS. No other clinical or demographic features were associated with either a history of CFS or HVL. The frequency of CFS in patients with other structural congenital causes of epilepsy did not differ from that in a general population. Although these findings show that hippocampal sclerosis is strongly associated with a history of CFS, they do not indicate whether this is a causal relationship. If CFS do cause some cases of hippocampal sclerosis, this can not be the only mechanism, as 64% of those with HVL gave no history of CFS. As diffuse HVL is more strongly associated with a history of CFS than focal HVL, it is also possible that CFS convert pre-existing congenital focal abnormalities into diffuse hippocampal sclerosis. Given the possibility that CFS may cause hippocampal damage and epilepsy, they require urgent medical intervention.

Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy

UNLABELLED To compare the incidence of foetal malformations (FMs) in pregnant women with epilepsy treated with different anti-epileptic drugs (AED) and doses, and the influence of seizures, family and personal history, and environmental factors. A prospective, observational, community-based cohort study. METHODS A voluntary, Australia-wide, telephone-interview-based register prospectively enrolling three groups of pregnant women: taking AEDs for epilepsy; with epilepsy not taking AEDs; taking AEDs for a non-epileptic indication. Four hundred and fifty eligible women were enrolled over 40 months. Three hundred and ninety six pregnancies had been completed, with 7 sets of twins, for a total of 403 pregnancy outcomes. RESULTS 354 (87.8%) pregnancy outcomes resulted in a healthy live birth, 26 (6.5%) had a FM, 4 (1%) a death in utero, 1 (0.2%) a premature labour with stillbirth, 14 (3.5%) a spontaneous abortion and 4 lost to follow-up. The FM rate was greater in pregnancies exposed to sodium valproate (VPA) in the first trimester (16.0%) compared with those exposed to all other AEDs (16.0% vs. 2.4%, P < 0.01) or no AEDs (16.0% vs. 3.1%, [Formula: see text] ). The mean daily dose of VPA taken in pregnancy with FMs was significantly greater than in those without (1,975 vs. 1,128 mg, P < 0.01). The incidence of FM with VPA doses >or= 1,100 mg was 30.2% vs. 3.2% with doses <1,100 mg (P <0.01). CONCLUSIONS There is a dose-effect relationship for FM and exposure to VPA during the first trimester of pregnancy, with higher doses of VPA associated with a significantly greater risk than with lower doses or with other AEDs. These results highlight the need to limit, where possible, the dose of VPA in pregnancy.

Evaluating the Utility of Inpatient Video‐EEG Monitoring

Summary:  Purpose: Inpatient video‐EEG monitoring (VEM) is widely used for the diagnosis, seizure classification, and presurgical evaluation of patients with seizure disorders. It is resource intensive and relatively expensive, so its utility continues to be debated. Few studies have specifically evaluated the utility of inpatient VEM in altering diagnosis or management of patients with seizure disorders. We sought to assess the proportion of patients for whom the preadmission diagnosis and management were altered after inpatient VEM of patients admitted for diagnostic and presurgical evaluation of seizure disorders.

Hippocampal Atrophy Is Not a Major Determinant of Regional Hypometabolism in Temporal Lobe Epilepsy

Summary: Purpose: The pathophysiologic basis for the [18F]fluorodeoxyglucose positron‐emission tomography (FDG‐PET) temporal lobe hypometabolism in patients with hippocampal sclerosis (HS) is uncertain. We tested the hypothesis that hippocampal atrophy, which is strongly correlated with hippocampal cell loss, is largely responsible for the regional hypometabolism in HS.

Epilepsy Surgery for Pathologically Proven Hippocampal Sclerosis Provides Long‐term Seizure Control and Improved Quality of Life

Summary:  Purpose: To examine long‐term seizure and quality‐of‐life outcome in a homogeneous group of patients after temporal lobectomy with pathologically proven hippocampal sclerosis (HS). Previous research has had limited follow‐up (generally <2 years) and has grouped patients across multiple pathologies.

Degree of left hippocampal atrophy correlates with severity of neuropsychological deficits

The relationship between the degree and distribution of hippocampal atrophy measured by volumetric magnetic resonance imaging and severity of memory deficits in 25 patients with temporal lobe epilepsy secondary to mesial temporal sclerosis was assessed. Hippocampal volumes were expressed as a ratio of smaller to larger, normal ratio greater than 0.95. Neuropsychology tests included: subtests of the WAIS-R, Rey Auditory Verbal Learning Task, Rey Figure and the Austin Maze. Degree of left hippocampal atrophy in patients with left temporal lobe epilepsy was associated with severity of verbal memory deficits as measured by RAVLT total recall (P < 0.05), delayed recall (P < 0.001), story recognition (P < 0.001), list recognition (P < 0.001) and final delayed recall (P < 0.001) and recall of the Rey Figure (P < 0.01). There was no association between degree of right hippocampal atrophy and any of the memory tests. Diffuse left hippocampal atrophy was associated with more severe verbal memory deficits than anterior atrophy. We conclude, the association between degree of left hippocampal atrophy and verbal memory provides further evidence of the predominant involvement of the left hippocampus in verbal memory. The finding of a relationship between degree of left hippocampal atrophy and measures of non-verbal function suggests these tests are dependent on verbal memory, or that mesial temporal sclerosis is a bilateral but asymmetrical condition.

Surgical treatment of patients with single and dual pathology: Relevance of lesion and of hippocampal atrophy to seizure outcome

Article abstract-Modern neuroimaging can disclose epileptogenic lesions in many patients with partial epilepsy and, at times, display the coexistence of hippocampal atrophy in addition to an extrahippocampal lesion (dual pathology). We studied the postoperative seizure outcome of 64 patients with lesional epilepsy (median follow-up, 30 months) and considered separately the surgical results in the 51 patients with a single lesion and in the 13 who had dual pathology. In patients with a single lesion, 85% were seizure free or significantly improved (Engels class I-II) when the lesion was totally removed compared with only 40% when there was incomplete resection (p < 0.007). All three patients with dual pathology who had both the lesion and the atrophic hippocampus removed became seizure free. In contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed at the lesion or at the hippocampus alone became seizure free (p < 0.05), although 4 of them showed significant improvement (Engels class II). We conclude that the outcome in patients with single epileptogenic lesions is usually dependent upon the completeness of lesion resection. In patients with dual pathology, surgery should, if possible, include resection of both the lesion and the atrophic hippocampus. NEUROLOGY 1997;48: 437-444