L. Anne Mitchell

Epileptology of the first-seizure presentation: a clinical, electroencephalographic, and magnetic resonance imaging study of 300 consecutive patients

BACKGROUND Prognosis and treatment of the first seizure depends on identification of a specific epilepsy syndrome, yet patients with first seizures are generally regarded as a homogeneous group. We studied whether it is possible to diagnose specific epilepsy syndromes promptly by use of standard clinical methods, electroencephalography (EEG) and magnetic resonance imaging (MRI). METHODS 300 consecutive adults and children presented with unexplained seizures. We systematically collected clinical data from patients and witnesses, and attempted to obtain an EEG within 24 h of the seizure. Where the EEG was negative, a sleep-deprived EEG was done. MRI was done electively. FINDINGS A generalised or partial epilepsy syndrome was clinically diagnosed in 141 (47%) patients. Subsequent analysis showed that only three of these clinical diagnoses were incorrect. Addition of the EEG data enabled us to diagnose an epilepsy syndrome in 232 (77%) patients. EEG within 24 h was more useful in diagnosis of epileptiform abnormalities than later EEG (51 vs 34%). Neuroimaging showed 38 epileptogenic lesions, including 17 tumours. There were no lesions in patients for whom generalised epilepsy was confirmed by EEG. Our final diagnoses were: generalised epilepsy (23% of patients); partial epilepsy (58%); and unclassified (19%). INTERPRETATION An epilepsy syndrome can be diagnosed in most first-seizure patients. Ideally, an EEG should be obtained within 24 h of the seizure followed by a sleep deprived EEG if necessary. MRI aids diagnosis and should be done for all patients except for those with idiopathic generalised epilepsies and for children with benign rolandic epilepsy.

Accuracy of dementia diagnosis—a direct comparison between radiologists and a computerized method

There has been recent interest in the application of machine learning techniques to neuroimaging-based diagnosis. These methods promise fully automated, standard PC-based clinical decisions, unbiased by variable radiological expertise. We recently used support vector machines (SVMs) to separate sporadic Alzheimers disease from normal ageing and from fronto-temporal lobar degeneration (FTLD). In this study, we compare the results to those obtained by radiologists. A binary diagnostic classification was made by six radiologists with different levels of experience on the same scans and information that had been previously analysed with SVM. SVMs correctly classified 95% (sensitivity/specificity: 95/95) of sporadic Alzheimers disease and controls into their respective groups. Radiologists correctly classified 65–95% (median 89%; sensitivity/specificity: 88/90) of scans. SVM correctly classified another set of sporadic Alzheimers disease in 93% (sensitivity/specificity: 100/86) of cases, whereas radiologists ranged between 80% and 90% (median 83%; sensitivity/specificity: 80/85). SVMs were better at separating patients with sporadic Alzheimers disease from those with FTLD (SVM 89%; sensitivity/specificity: 83/95; compared to radiological range from 63% to 83%; median 71%; sensitivity/specificity: 64/76). Radiologists were always accurate when they reported a high degree of diagnostic confidence. The results show that well-trained neuroradiologists classify typical Alzheimers disease-associated scans comparable to SVMs. However, SVMs require no expert knowledge and trained SVMs can readily be exchanged between centres for use in diagnostic classification. These results are encouraging and indicate a role for computerized diagnostic methods in clinical practice.

Clinical and Imaging Heterogeneity of Polymicrogyria: A Study of 328 Patients.

Polymicrogyria is one of the most common malformations of cortical development and is associated with a variety of clinical sequelae including epilepsy, intellectual disability, motor dysfunction and speech disturbance. It has heterogeneous clinical manifestations and imaging patterns, yet large cohort data defining the clinical and imaging spectrum and the relative frequencies of each subtype are lacking. The aims of this study were to determine the types and relative frequencies of different polymicrogyria patterns, define the spectrum of their clinical and imaging features and assess for clinical/imaging correlations. We studied the imaging features of 328 patients referred from six centres, with detailed clinical data available for 183 patients. The ascertainment base was wide, including referral from paediatricians, geneticists and neurologists. The main patterns of polymicrogyria were perisylvian (61%), generalized (13%), frontal (5%) and parasagittal parieto-occipital (3%), and in 11% there was associated periventricular grey matter heterotopia. Each of the above patterns was further divided into subtypes based on distinguishing imaging characteristics. The remaining 7% were comprised of a number of rare patterns, many not described previously. The most common clinical sequelae were epileptic seizures (78%), global developmental delay (70%), spasticity (51%) and microcephaly (50%). Many patients presented with neurological or developmental abnormalities prior to the onset of epilepsy. Patients with more extensive patterns of polymicrogyria presented at an earlier age and with more severe sequelae than those with restricted or unilateral forms. The median age at presentation for the entire cohort was 4 months with 38% presenting in either the antenatal or neonatal periods. There were no significant differences between the prevalence of epilepsy for each polymicrogyria pattern, however patients with generalized and bilateral forms had a lower age at seizure onset. There was significant skewing towards males with a ratio of 3:2. This study expands our understanding of the spectrum of clinical and imaging features of polymicrogyria. Progression from describing imaging patterns to defining anatomoclinical syndromes will improve the accuracy of prognostic counselling and will aid identification of the aetiologies of polymicrogyria, including genetic causes.

The Localization and Lateralization of Memory Deficits in Children with Temporal Lobe Epilepsy

Summary:  Purpose: It is often reported that children with temporal lobe epilepsy (TLE) experience nonlateralized memory impairments. However, many of these studies have been exploratory and not based on memory theory. Further, differences between mesial and lateral subgroups have not been adequately examined. This study aimed to discern more specific patterns of memory impairment in children with TLE.

Long‐term seizure outcome and risk factors for recurrence after extratemporal epilepsy surgery

Purpose:  We aimed to assess long‐term seizure outcome and risk factors for seizure recurrence in a cohort of patients who have undergone extratemporal resection for management of refractory seizures.

Early seizures after temporal lobectomy predict subsequent seizure recurrence

Patients are understandably anxious if seizures occur immediately after temporal lobectomy. Such “neighborhood” seizures are commonly regarded as irrelevant to seizure outcome and discounted in outcome measurement. We conducted an in‐depth examination of early postoperative seizures (<28 days) and outcome. The risk of recurrence at one postoperative year was calculated using Poisson regression, and statistical adjustments were made for preoperative pathology. Of 321 patients, 69 (22%) experienced early postoperative seizures. These early seizures were associated with subsequent seizure recurrence (rate ratio [RR] 5.9; 95% confidence interval [CI], 4.1–8.4). Among patients with early seizures, the only significant factor was the presence of seizure precipitants, which was associated with a lower recurrence risk. However, when compared with patients with no early seizures, those with precipitants to early seizures had a higher risk of recurrence (RR, 3.0; 95% CI, 1.8–5.2). The risk was higher again for patients without precipitants to early seizures (RR, 7.6; 95% CI, 5.0–11.5). Early seizures and other seizure recurrences in the first postoperative year did not differ in their effect on subsequent outcome (X2 [3] = 3.4, p = 0.33). We conclude that early postoperative seizures are associated with subsequent seizure recurrence. These findings have implications for patient counseling and the measurement of outcome. Ann Neurol 2005;57:283–288

Correlation between language organization and diffusion tensor abnormalities in refractory partial epilepsy.

Summary:  Purpose: Atypical language organization is more frequently found in patients with refractory partial epilepsy than in healthy controls; however, the reasons for this are not well known. Here we assess the relation between language laterality index (LI) and white‐matter tract changes.

The ASPECTS template is weighted in favor of the striatocapsular region

The extent of cerebral infarction correlates with increased risk of intracerebral hemorrhage (ICH) following recombinant tissue plasminogen activator (rt-PA) administration. The Alberta Stroke Program Early CT Score (ASPECTS) is a widely used, validated method which assesses involvement of 10 selected regions of the MCA territory. An ASPECTS score >7 is associated with a higher risk of ICH following thrombolysis than lower scores. To understand the internal structure of the ASPECTS template better, we estimated the infarct volume corresponding to each region. We hypothesized that, in the ASPECTS scoring system, the striatocapsular region is weighted disproportionally. Four experienced radiologists rated individual ASPECTS regions on subacute CT images (day 5-day 10) of 19 patients with MCA territory stroke. Infarct volume was determined from manual segmentation of infarcts on CT images. Linear regression was used to estimate the regional volume associated with each ASPECTS region. The ASPECTS regions are weighted unequally with the striatocapsular region accounting for 21% of the MCA territory infarct volume. Together, the 10 ASPECTS regions account for approximately 51% of the maximum MCA infarct territory volume. These findings should provide impetus for research to develop a scoring system explicitly based on regional hemorrhage risk as an aid to selecting patients for thrombolysis.

Small temporal pole encephaloceles: A treatable cause of ''lesion negative'' temporal lobe epilepsy

Epilepsy due to encephaloceles of the temporal pole may be an under recognized, treatable cause of refractory temporal lobe epilepsy (TLE). We describe three adult patients initially labeled “lesion negative” TLE. In all, video–electroencephalography (EEG) revealed ictal theta in the left temporal region and positron emission tomography (PET) showed temporal lobe hypometabolism, but neuropsychology revealed preserved verbal memory. Close inspection of structural magnetic resonance imaging (MRI) suggested subtle abnormalities at the tip of the left temporal lobe. High resolution computed tomography (CT) confirmed bony defects in the inner table of the skull. 3T MRI with fine coronal and sagittal slices indicated cerebrospinal fluid (CSF) and brain tissue protruding into the defects. All proceeded to resection of the temporal tip and became seizure free. Patients with “lesion negative” TLE should have careful review of images covering the temporal pole. If encephalocele is suspected, further imaging with high‐resolution CT and MRI can be helpful. Temporal polar resection, sparing mesial structures, appears to be curative.

Occurrence of Hippocampal Sclerosis: Is One Hemisphere or Gender More Vulnerable?

Summary: Purpose: We analyzed a large group of patients investigated for suspected seizures to test whether gender or side are important factors in the origins of hippocampal sclerosis (HS).