MRI-negative PET-positive temporal lobe epilepsy (TLE) and mesial TLE differ with quantitative MRI and PET: a case control study

Background: 'MRI negative PET positive temporal lobe epilepsy' represents a substantial minority of temporal lobe epilepsy (TLE). Clinicopathological and qualitative imaging differences from mesial temporal lobe epilepsy are reported. We aimed to compare TLE with hippocampal sclerosis (HS+ve) and non lesional TLE without HS (HS-ve) on MRI, with respect to quantitative FDG-PET and MRI measures.

Methods: 30 consecutive HS-ve patients with well-lateralised EEG were compared with 30 age- and sex-matched HS+ve patients with well-lateralised EEG. Cerebral, cortical lobar and hippocampal volumetric and co-registered FDG-PET metabolic analyses were performed.

Results: There was no difference in whole brain, cerebral or cerebral cortical volumes. Both groups showed marginally smaller cerebral volumes ipsilateral to epileptogenic side (HS-ve 0.99, p = 0.02, HS+ve 0.98, p < 0.001). In HS+ve, the ratio of epileptogenic cerebrum to whole brain volume was less (p = 0.02); the ratio of epileptogenic cerebral cortex to whole brain in the HS+ve group approached significance (p = 0.06). Relative volume deficits were seen in HS+ve in insular and temporal lobes. Both groups showed marked ipsilateral hypometabolism (p < 0.001), most marked in temporal cortex. Mean hypointensity was more marked in epileptogenic-to-contralateral hippocampus in HS+ve (ratio: 0.86 vs 0.95, p < 0.001). The mean FDG-PET ratio of ipsilateral to contralateral cerebral cortex however was low in both groups (ratio: HS-ve 0.97, p < 0.0001; HS+ve 0.98, p = 0.003), and more marked in HS-ve across all lobes except insula.

Conclusion: Overall, HS+ve patients showed more hippocampal, but also marginally more ipsilateral cerebral and cerebrocortical atrophy, greater ipsilateral hippocampal hypometabolism but similar ipsilateral cerebral cortical hypometabolism, confirming structural and functional differences between these groups.

Hippocampal deformation mapping in MRI-negative PET-positive temporal lobe epilepsy

Objectives: To compare hippocampal surface structure, using large deformation high dimensional mapping (HDM-LD), in subjects with temporal lobe epilepsy (TLE) with (HS+ve) and without (HS−ve) hippocampal sclerosis.

Methods: The study included 30 HS−ve subjects matched with 30 HS+ve subjects from the previously reported epilepsy patient cohort. To control for normal right–left asymmetries of hippocampal surface structure, subjects were regrouped based on laterality of onset of epileptic seizures and presence of HS. Gender ratio, age, duration of epilepsy and seizure frequency were calculated for each of the four groups. Final HDM-LD surface maps of the right and left TLE groups were compared to define differences in subregional hippocampal involvement within the groups.

Results: There were no significant differences in comparisons of the left TLE (left HS−ve compared with HS+ve) or right TLE (right HS−ve compared with HS+ve) groups with respect to age, duration of epilepsy or seizure severity scores. HDM-LD maps showed accentuated surface changes over the lateral hippocampal surface, in the region of the Sommer sector, in the hippocampi affected by HS. However, HS−ve hippocampi showed maximal surface changes in a different pattern, and did not involve the region of Sommer sector.

Conclusion: We conclude that differences in segmental volume loss between the HS−ve and HS+ve groups are suggestive that the underlying pathophysiology of hippocampal changes in the two groups is different, and not related to chronic seizure duration or severity.

Sequential 123-I-iododexetimide scans in temporal lobe epilepsy: comparison with neuroimaging scans (MR imaging and 18-F-FDG-PET imaging)

Purpose Muscarinic acetylcholine receptors (mAChRs) play an important role in the generation of seizures. Single-photon emission computed tomography (SPECT) with ¹²³I-iododexetimide (IDEX) depicts tracer uptake by mAChRs. Our aims were to: (a) determine the optimum time for interictal IDEX SPECT imaging; (b) determine the accuracy of IDEX scans in the localisation of seizure foci when compared with video EEG and MR imaging in patients with temporal lobe epilepsy (TLE); (c) characterise the distribution of IDEX binding in the temporal lobes and (d) compare IDEX SPECT and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in identifying seizure foci.
Methods We performed sequential scans using IDEX SPECT imaging at 0, 3, 6 and 24 h in 12 consecutive patients with refractory TLE undergoing assessment for epilepsy surgery. Visual and region of interest analyses of the mesial, lateral and polar regions of the temporal lobes were used to compare IDEX SPECT, FDG PET and MR imaging in seizure onset localisation.
Results The 6-h IDEX scan (92%; κappa=0.83, p=0.003) was superior to the 0-h (36%; kappa=0.01, p>0.05), 3-h (55%;κappa=0.13, p>0.05) and 24-h IDEX scans in identifying the temporal lobe of seizure origin. The 6-h IDEX scan correctly predicted the temporal lobe of seizure origin in two patients who required intracranial EEG recordings to define the seizure onset. Reduced ligand binding was most marked at the temporal pole and mesial temporal structures. IDEX SPECT was superior to interictal FDG PET (75%; κappa=0.66, p=0.023) in seizure onset localisation. MR imaging was non-localising in two patients in whom it was normal and in another patient in whom there was bilateral symmetrical hippocampal atrophy.
Conclusion The 6-h IDEX SPECT scan is a viable alternative to FDG PET imaging in seizure onset localisation in TLE.

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

Summary: 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 ≥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.

Beta-lactam antibiotics as a possible novel therapy for managing epilepsy and autism, a case report and review of literature

Autism is a disorder of unknown etiology. There are few FDA approved medications for treating autism. Co-occurring autism and epilepsy is common, and glutamate antagonists improve some symptoms of autism. Ceftriaxone, a beta-lactam antibiotic, increases the expression of the glutamate transporter 1 which decreases extracellular glutamate levels. It is hypothesized that modulating astrocyte glutamate transporter expression by ceftriaxone or cefixime might improve some symptoms of autism. This case report of a child with autism and epilepsy suggests a decrease in seizures after taking cefixime

Response of obsessive compulsive disorder to carbamazepine in two patients with comorbid epilepsy.

An association between epilepsy and obsessive compulsive disorder (OCD) has been noted. The response of two patients with OCD and comorbid epilepsy to carbamazepine is reported. It is hypothesized that obsessive compulsive symptoms may be a variant of epileptiform forced thinking in a subgroup of patients, and may be preferentially responsive to anticonvulsant therapy.

Burden of epilepsy: a prevalence-based cost of illness study of direct, indirect and intangible costs for epilepsy

OBJECTIVES: We aimed to gauge the burden of epilepsy in China from a societal perspective by estimating the direct, indirect and intangible costs. METHODS: Patients with epilepsy and controls were enrolled from two tertiary hospitals in China. Patients were asked to complete a Cost-of-Illness (COI), Willingness-to-Pay (WTP) questionnaires, two utility elicitation instruments and Mini Mental State Examination (MMSE). Healthy controls only completed WTP questionnaire, and utility instruments. Univariate analyses were performed to investigate the differences in cost on the basis of different variables, while multivariate analysis was undertaken to explore the predictors of cost/cost component. RESULTS: In total, 141 epilepsy patients and 323 healthy controls were recruited. The median total cost, direct cost and indirect cost due to epilepsy were US$949.29, 501.34 and 276.72, respectively. Particularly, cost of anti-epileptic drugs (AEDs) (US$394.53) followed by cost of investigations (US$59.34), cost of inpatient and outpatient care (US$9.62) accounted for the majority of the direct medical costs. While patients' (US$103.77) and caregivers' productivity costs (US$103.77) constituted the major component of indirect cost. The intangible costs in terms of WTP value (US$266.07 vs. 88.22) and utility (EQ-5D, 0.828 vs. 0.923; QWB-SA, 0.657 vs. 0.802) were both substantially higher compared to the healthy subjects. CONCLUSIONS: Epilepsy is a cost intensive disease in China. According to the prognostic groups, drug-resistant epilepsy generated the highest total cost whereas patients in seizure remission had the lowest cost. AED is the most costly component of direct medical cost probably due to 83% of patients being treated by new generation of AEDs.

Health-related quality of life and willingness to pay per quality-adjusted life-Year threshold—A study in patients with epilepsy in China

Objectives
To assess the health-related quality of life (HRQOL) and willingness to pay (WTP) per quality-adjusted life-year (QALY) amount of patients with epilepsy in China.
Methods
Adults with epilepsy and a healthy control were recruited in two tertiary hospitals in China. Participants completed two indirect utility elicitation instruments (Quality of Well-being Scale-self administered version and EuroQol five-dimensional questionnaire) and a WTP questionnaire. Correlations between sociodemographic or epilepsy-specific variables (age of epilepsy onset, duration of epilepsy, seizure types, types of antiepileptic drug treatment, etc.) and HRQOL or WTP/QALY were assessed to identify the candidate predictor. Multiple linear regression models were adopted to investigate the predictive performances of identified candidate predictors. Data analyses were performed on SPSS 20.0 (SPSS, Inc., Chicago, IL).
Results
For utilities of both the Quality of Well-being Scale-self administered version and the EuroQol five-dimensional questionnaire, patients with epilepsy had statistically lower values than did the control group (P < 0.0001). In terms of the WTP/month, the percentage of WTP accounting for the monthly income and the WTP/QALY values from the epilepsy group were substantially higher than those from the control group (P < 0.0001).
View the MathML sourceWTP/QALY=12×WTPMonth1−Utility(CurrentHealth)
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The multiple linear regression model identified working status (P = 0.05), seizure types (P = 0.022), income (P = 0.006), and self-rating health state (P < 0.05) as predictors of HRQOL while income (P = 0.000) and self-rating health state (P < 0.05) statistically contributed to the variations in WTP/QALY value for the epilepsy group.
Conclusions
Patients with epilepsy had substantially lower HRQOL than did the healthy population.

Emerging drugs for partial-onset epilepsy: a review of brivaracetam

There are more than 12 new antiepileptic drugs approved in the last 2 decades. Even with these newer agents, seizure remission is still unachievable in around 30% of patients with partial-onset seizures (POS). Brivaracetam (BRV) is chemically related to levetiracetam (LEV) and possesses a strong binding affinity for the synaptic vesicle protein 2A tenfold above that of LEV, and other possible modes of antiepileptic actions. BRV is now under Phase III development for POS, but data from one Phase III trial also suggested its potential efficacy for primary generalized seizures. The purpose of this review is to provide updated information on the mechanisms of action of the available antiepileptic drugs, with a focus on BRV to assess its pharmacology, pharmacokinetics, clinical efficacy, safety, and tolerability in patients with uncontrolled POS. To date, six Phase IIb and III clinical trials have been performed to investigate the efficacy, safety, and tolerability of BRV as an adjunctive treatment for patients with POS. Generally, BRV was well tolerated and did not show significant difference in safety profile, compared to placebo. The efficacy outcomes of BRV, although not consistent across trials, did indicate that BRV was a promising add-on therapy for patients with POS. In conclusion, the many favorable attributes of BRV, like its high oral efficacy, good tolerability, dosing regimen, and minimal drug interaction, make it a promising antiepileptic therapy for patients with uncontrolled partial-onset epilepsy.

Can the direct medical cost of chronic disease be transferred across different countries? Using cost-of-illness studies on type 2 diabetes, epilepsy and schizophrenia as examples

OBJECTIVES: To systematically review cost of illness studies for schizophrenia (SC), epilepsy (EP) and type 2 diabetes mellitus (T2DM) and explore the transferability of direct medical cost across countries.

METHODS: A comprehensive literature search was performed to yield studies that estimated direct medical costs. A generalized linear model (GLM) with gamma distribution and log link was utilized to explore the variation in costs that accounted by the included factors. Both parametric (Random-effects model) and non-parametric (Boot-strapping) meta-analyses were performed to pool the converted raw cost data (expressed as percentage of GDP/capita of the country where the study was conducted).

RESULTS: In total, 93 articles were included (40 studies were for T2DM, 34 studies for EP and 19 studies for SC). Significant variances were detected inter- and intra-disease classes for the direct medical costs. Multivariate analysis identified that GDP/capita (p<0.05) was a significant factor contributing to the large variance in the cost results. Bootstrapping meta-analysis generated more conservative estimations with slightly wider 95% confidence intervals (CI) than the parametric meta-analysis, yielding a mean (95%CI) of 16.43% (11.32, 21.54) for T2DM, 36.17% (22.34, 50.00) for SC and 10.49% (7.86, 13.41) for EP.

CONCLUSIONS: Converting the raw cost data into percentage of GDP/capita of individual country was demonstrated to be a feasible approach to transfer the direct medical cost across countries. The approach from our study to obtain an estimated direct cost value along with the size of specific disease population from each jurisdiction could be used for a quick check on the economic burden of particular disease for countries without such data.