Bilateral Magnetic Resonance Imaging-Determined Hippocampal Atrophy and Verbal Memory Before and After Temporal Lobectomy

Summary: We investigated pre- and postoperative verbal memory in temporal lobectomy patients who had volumetrically symmetric hippocampi. Pre- and postoperative verbal memory data based on the Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS-R) were obtained from 15 left and 18 right temporal lobectomy patients. The difference between hippocampal volumes (R/L) was between -0.1 and 0.3 cm³, which is indeterminate for lateralizing hippocampal atrophy. Patients were divided into four groups based on side of operation and combined hippocampal volume expressed as a function of total intracranial volume (R + L volume/total intracranial volume). Patients with a combined hippocampal volume that was smaller than any combined hippocampal value of a normal control group were defined as bilaterally atrophic. Left temporal lobectomy patients demonstrated the expected decrease in verbal memory postoperatively regardless of whether the volumetrically symmetric hippocampi were nonatrophic or atrophic. Left temporal lobectomy patients with bilaterally atrophic hippocampi, however, had the poorest verbal memory before and after operation. Right temporal lobectomy patients tended to have improved verbal memory after operation whether or not the volumetrically symmetric hippocampi were atrophic. We conclude that side of operation is a more potent predictor of verbal memory outcome than is hippocampal atrophy when hippocampi are bilaterally symmetric and that left temporal lobectomy patients with bilateral atrophy may be at risk for greater functional deficits after operation.     

Alterations of Glial Cell Function in Temporal Lobe Epilepsy

Summary: Purpose : Comparison of extracellular K⁺ regulation in sclerotic and nonsclerotic epileptic hippocampus.
Methods : Measurements of K⁺ signals with double-barreled K⁺-selective reference microelectrodes in area CA1 of slices from human and rat hippocampus, induction of increases in extracellular potassium concentration by repetitive alvear stimulation or iontophoresis, and block of inward-rectifying and background K⁺ channels in astrocytes by barium.
Results : In the CA1 pyramidal layer from normal rat hippocampus, barium augmented extracellular K⁺ accumulation induced by iontophoresis or antidromic stimulation in a dose-dependent manner. Similarly, barium augmented stimulusinduced K⁺ signals from nonsclerotic hippocampi (human mesial temporal lobe epilepsy). In contrast, barium failed to do so in sclerotic hippocampi (human mesial temporal lobe epilepsy, rat pilocarpine model).
Conclusions : Our findings suggest that in areas of reduced neuronal density (hippocampal sclerosis), glial cells adapt to permit rather large increases in extracellular potassium accumulation. Such increases might be involved in the transmission of activity through the sclerotic area.     

Automated MRI analysis for identification of hippocampal atrophy in temporal lobe epilepsy

Background:   Hippocampal sclerosis is frequently associated with hippocampal atrophy (HA), which is often observed on routine magnetic resonance imaging (MRI) of patients with medial temporal lobe epilepsy (MTLE). Manual morphometry of the hippocampus is sensitive to detecting HA, but is time-consuming and prone to operator error. Automated MRI morphometry has the potential to provide rapid and accurate assistance in the clinical detection of HA.
Methods:   We performed a voxel-based morphometry analysis of 23 consecutive subjects with MTLE and 58 matched controls. Images from randomly selected 34 controls were used to create mean and standard deviation images of gray matter volume. Voxel-wise standardized Z-score hippocampal images from patients and the remaining 24 controls were cross-checked with receiver operating characteristic (ROC) curves to evaluate sensitivity versus one-specificity rate for a binary classifier (atrophied versus normal hippocampi).
Results:   The ipsilateral hippocampi of patients with MTLE displayed a significantly lower mean Z-score compared to the hippocampi of controls [F(2,67)  = 33.014, p < 0.001, Tukey HSD < 0.001]. A classifier using the hippocampal gray matter Z-scores to discriminate between atrophied and normal hippocampi yielded a fitted ROC = 97.3, traditionally considered an excellent discriminator, with a standard error of classification of 1.173 individuals if  100  patients and  100  controls are studied.
Conclusion:   Automatic morphometry can be potentially used as a clinical tool to assist the detection of HA in patients with MTLE. It can provide a quantifiable estimative of atrophy, which can aid in the decision about the presence of clinically relevant HA.     

Correlation of Hippocampal Neuronal Density and FDG-PET in Mesial Temporal Lobe Epilepsy

Summary: Purpose: Interictal [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) reveals regional hypometabolism in 60–80% of patients with mesial temporal lobe epilepsy (MTLE). The extent of hypometabolism generally extends beyond the epileptogenic zone. The pathophysiology underlying this widespread change is unknown. This study evaluated the relation between hippocampal neuronal loss and hypometabolism in patients with MTLE.
Methods: Forty-three patients with MTLE after anterior temporal lobectomy were included. Pathology demonstrated mesial temporal sclerosis (n = 41) or endfolium sclerosis (n = 2). Interictal FDG-PET scans were graded by visual analysis on a scale ranging from normal (grade 1) to severe (grade 5) hypometabolism. Neuronal counting was performed in the subiculum, hippocampal subfields, and dentate granular cell layer (DG). Neuronal density of patients was compared with that of seven autopsy controls. Data were compared by using Student's t tests and Kruskal-Wallis one-way analysis of variance (ANOVA).
Results: Significant neuronal loss in CA1 through CA4 and DG was found in patients compared with controls. Neuronal density in the subiculum, CA1, CA4, and DG did not correlate with severity of hypometabolism. However, patients with abnormal FDG-PET had higher neuronal density in CA2 and CA3 versus patients with normal studies.
Conclusions: This study supports a previous observation that degree of FDG-PET hypometabolism does not parallel severity of hippocampal neuronal loss in MTLE.     

Bilateral hippocampal atrophy: consequences to verbal memory following temporal lobectomy

BACKGROUND: Bilateral hippocampal damage is a risk factor for memory decline after anterior temporal lobectomy (ATL). OBJECTIVE: To investigate verbal memory outcome in patients with temporal lobe epilepsy (TLE) with either unilateral or bilateral hippocampal atrophy as measured by MRI. METHODS: The authors selected 60 patients with TLE who had undergone ATL (left = 31, right = 29). They determined normalized MRI hippocampal volumes by cursor tracing 1.5-mm slices from three-dimensional MRI acquisition. Hippocampal volumes were defined as atrophic if the volumes were below 2 SD for control subjects. Bilateral hippocampal atrophy was present in 10 patients with left TLE and 11 patients with right TLE. The authors assessed acquisition, retrieval, and recognition components of verbal memory both before and after ATL. RESULTS: Groups did not differ across age, education, intelligence, age at seizure onset, or seizure duration. Seizure-free rates after ATL were 70% or higher for all groups. Before surgery, patients with left TLE displayed worse verbal acquisition performance compared with patients with right TLE. Patients with left TLE with bilateral hippocampal volume loss displayed the lowest performance across all three memory components. After surgery, both groups of patients with left TLE exhibited worse verbal memory outcome compared with patients with right TLE. Bilateral hippocampal atrophy did not worsen outcome in the patients with right TLE. A higher proportion of patients with left TLE with bilateral hippocampal atrophy experienced memory decline compared with the other TLE groups. CONCLUSION: Bilateral hippocampal atrophy in the presence of left TLE is associated with worse verbal memory before and after ATL compared with patients with unilateral hippocampal volume loss or right TLE with bilateral hippocampal volume loss.     

Subfield atrophy pattern in temporal lobe epilepsy with and without mesial sclerosis detected by high-resolution MRI at 4 Tesla: Preliminary results

Purpose:   High-resolution magnetic resonance imaging (MRI) at 4 Tesla depicts details of the internal structure of the hippocampus not visible at 1.5 Tesla, and so allows for in vivo parcellation of different hippocampal subfields. The aim of this study was to test if distinct subfield atrophy patterns can be detected in temporal lobe epilepsy (TLE) with mesial temporal sclerosis (TLE-MTS) and without (TLE-no) hippocampal sclerosis.
Methods:   High-resolution T₂-weighted hippocampal images were acquired in 34 controls: 15 TLE-MTS and 18 TLE-no. Entorhinal cortex (ERC), subiculum (SUB), CA1, CA2, and CA3, and dentate (CA3&DG) volumes were determined using a manual parcellation scheme.
Results:   TLE-MTS had significantly smaller ipsilateral CA1, CA2, CA3&DG, and total hippocampal volume than controls or TLE-no. Mean ipsilateral CA1 and CA3&DG z-scores were significantly lower than ipsilateral CA2, ERC, and SUB z-scores. There were no significant differences between the various subfield or hippocampal z-scores on either the ipsi- or the contralateral side in TLE-no. Using a z-score ≤−2.0 to identify severe volume loss, the following atrophy patterns were found in TLE-MTS: CA1 atrophy, CA3&DG atrophy, CA1 and CA3&DG atrophy, and global hippocampal atrophy. Significant subfield atrophy was found in three TLE-no: contralateral SUB atrophy, bilateral CA3&DG atrophy, and ipsilateral ERC and SUB atrophy.
Discussion:   Using a manual parcellation scheme on 4 Tesla high-resolution MRI, we found the characteristic ipsilateral CA1 and CA3&DG atrophy described in TLE-MTS. Seventeen percent of the TLE-no had subfield atrophy despite normal total hippocampal volume. These findings indicate that high-resolution MRI and subfield volumetry provide superior information compared to standard hippocampal volumetry.     

Lower postprandial gastric volume response in diabetic patients with vagal neuropathy

Poor relaxation in the stomach after a meal may contribute to disturbed gastric emptying and abdominal discomfort in patients with diabetes mellitus. In this study we aimed to compare barostat-recorded postprandial volume responses in these patients to those in healthy controls, and to study the relationship between the proximal volume responses, antral filling and vagal neuropathy.
We compared 14 consecutively recruited patients with type 1 diabetes mellitus (DM) to 18 healthy controls (HC) with respect to meal-induced gastric volume response assessed by a barostat, antral area recorded by ultrasound, and vagal tone assessed by respiratory sinus arrhythmia (RSA).
Meal-induced volume repsponse of the proximal stomach (area under time–volume curve 0–30 min) was significantly (P = 0.04) lower in DM than in HC, 49.4 min.mL ± 60.7 vs. 114.9 min.mL ± 100.8. Antral area was significantly larger in DM than in HC, both fasting (4.3 cm² ± 1.9 vs. 3.0 cm² ± 0.9) and 10 min after ingestion of meat soup (11.8 cm² ± 3.4 vs. 8.8 cm² ± 2.9), P = 0.03 and P = 0.02, respectively. Vagal tone was significantly (P = 0.01) lower in DM than in HC, 3.7 beats min⁻¹ ± 2.3 vs. 6.1 beats min⁻¹ ± 2.2. No significant correlation was observed between the proximal volume responses and antral widening. Maximal gastric volume response correlated significantly with vagal tone (r = 0.77, P = 0.002). Conclusions: patients with diabetes mellitus type 1 have impaired meal-induced volume response, possibly as a consequence of reduced vagal tone.     

Bilateral Hippocampal Atrophy in Medial Temporal Lobe Epilepsy

Summary: Quantitative evidence of hippocampal atrophy has been correlated with site of seizure onset, hippocampal neuronal loss, and seizure relief after resection. Most studies have quantified hippocampal atrophy using ratios or differences between right and left hippocampal values. However, bilateral hippocampal atrophy may remain undetected by these techniques. To assess the frequency and implications of bilateral hippocampal atrophy, we studied absolute hippocampal volumes in 53 temporal lobectomy patients who had undergone intracranial electroencephalogram recordings preoperatively. Coronal images were constructed perpendicular to the longitudinal axis of the hippocampus. Atrophy was defined as >2 SD below control values in the volume of the posterior. 5 cm of the hippocampus. Five of 53 patients (9%)had bilateral hippocampal atrophy; four of these cases were undetected by ratios. Surgery was performed on the side of ictal onset in all five patients; four have been seizure-free for >2 years. These results suggest that (a) mesial temporal sclerosis can be present bilaterally and may go undetected by hippocampal ratio or difference measures; (b) ab-solute hippocampal volume values as well as ratios are needed to detect all patients with bilateral hippocampal atrophy; and (c) temporal lobectomy is not contraindicated in patients with bilateral hippocampal atrophy, but success depends on electroencephalographic documentation of the side of predominant ictal onset.     

Sunday, December 3, 2006Poster Session I7:30 a.m.–4:30 p.m.

¹ Abuhuziefa Abubakr , ¹ Ilse Wambacq , and ¹ Humaira J. Butt (   ¹ New Jersey Neuroscience Institute, Seton Hall University for Graduate Medical Education, Edison, NJ )
Rationale: Hyperventilation is considered one of the activation procedures that provoke epileptic potentials and clinical seizures. Therefore we evaluated the effectiveness of routine 3 and 5 min. HV in all patients admitted to EMU.
Methods: Retrospective record review of all patients admitted for long-term video EEG at JFK hospital between October 2001 and Dec. 2004 were included. All patients underwent routine 3 and 5 min HV as part of the evaluation of their clinical spells.
Results: A total of 475 patients were included in the evaluation. There were 193 Males and 282 Females, age range between 1–89 yrs. Out of 475 patients, 165 patients did not have a clinical event or EEG abnormalities and 92 had non-epileptic event. In the remaining 218 patients, there were 16 patients with PNES and six of them (18.7) had a clinical event during HV. Similarly 9 out of 43 patients (20.2%) with primary generalized epilepsy had abnormal EEG and 2 of them had clinical seizures in addition to the abnormal EEG. However, out of the 159 patients with partial seizures there is only one patient who had abnormal EEG (focal ED) without a clinical event during HV.
Conclusions: This study demonstrates that routine HV generally has very low yield in the EMU. This finding also lends it support to the notion that partial seizures are relatively resistant to the HV activation.     

Subcortical and cerebellar atrophy in mesial temporal lobe epilepsy revealed by automatic segmentation

PURPOSE: To determine the validity and utility of using automated subcortical segmentation to identify atrophy of the hippocampus and other subcortical and cerebellar structures in patients with mesial temporal lobe epilepsy (MTLE). METHODS: Volumetric MRIs were obtained on 21 patients with MTLE (11 right, 10 left) and 21 age- and gender-matched healthy controls. Labeling of subcortical and cerebellar structures was accomplished using automated reconstruction software (FreeSurfer). Multivariate analysis of covariance (MANCOVA) was used to explore group differences in intracranial-normalized, age-adjusted volumes and structural asymmetries. Step-wise discriminant function analysis was used to identify the linear combination of volumes that optimized classification of individual subjects. RESULTS: Results revealed the expected reduction in hippocampal volume on the side ipsilateral to the seizure focus, as well as bilateral reductions in thalamic and cerebellar gray matter volume. Analysis of structural asymmetries revealed significant asymmetry in the hippocampus and putamen in patients compared to controls. The discriminant function analysis revealed that patients with right and left MTLE were best distinguished from one another using a combination of subcortical volumes that included the right and left hippocampus and left thalamus (91-100% correct classification using cross-validation). DISCUSSION: Volumetric data obtained with automated segmentation of subcortical and cerebellar structures approximate data from previous studies based on manual tracings. Our data suggest that automated segmentation can provide a clinically useful means of evaluating the nature and extent of structural damage in patients with MTLE and may increase diagnostic classification of patients, especially when hippocampal atrophy is mild.