Summary
Objective
To describe mesial temporal lobe ablated volumes, verbal memory, and surgical outcomes in patients with medically intractable mesial temporal lobe epilepsy (mTLE) treated with ...magnetic resonance imaging (MRI)–guided stereotactic laser interstitial thermal therapy (LiTT).
Methods
We prospectively tracked seizure outcome in 20 patients at Thomas Jefferson University Hospital with drug‐resistant mTLE who underwent MRI‐guided LiTT from December 2011 to December 2014. Surgical outcome was assessed at 6 months, 1 year, 2 years, and at the most recent visit. Volume‐based analysis of ablated mesial temporal structures was conducted in 17 patients with mesial temporal sclerosis (MTS) and results were compared between the seizure‐free and not seizure‐free groups.
Results
Following LiTT, proportions of patients who were free of seizures impairing consciousness (including those with auras only) are as follows: 8 of 15 patients (53%, 95% confidence interval CI 30.1–75.2%) after 6 months, 4 of 11 patients (36.4%, 95% CI 14.9–64.8%) after 1 year, 3 of 5 patients (60%, 95% CI 22.9–88.4%) at 2‐year follow‐up. Median follow‐up was 13.4 months after LiTT (range 1.3 months to 3.2 years). Seizure outcome after LiTT suggests an all or none response. Four patients had anterior temporal lobectomy (ATL) after LiTT; three are seizure‐free. There were no differences in total ablated volume of the amygdalohippocampus complex or individual volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and fusiform gyrus between seizure‐free and non–seizure‐free patients. Contextual verbal memory performance was preserved after LiTT, although decline in noncontextual memory task scores were noted.
Significance
We conclude that MRI‐guided stereotactic LiTT is a safe alternative to ATL in patients with medically intractable mTLE. Individualized assessment is warranted to determine whether the reduced odds of seizure freedom are worth the reduction in risk, discomfort, and recovery time. Larger prospective studies are needed to confirm our preliminary findings, and to define optimal ablation volume and ideal structures for ablation.
Objective
The widely prescribed anticonvulsants phenytoin and carbamazepine are potent inducers of cytochrome P450 enzymes, which are involved in cholesterol synthesis. We sought to determine whether ...these drugs have an effect on cholesterol and other serological markers of vascular risk.
Methods
We recruited 34 epilepsy patients taking carbamazepine or phenytoin in monotherapy whose physicians had elected to change treatment to one of the noninducing anticonvulsants lamotrigine or levetiracetam. Fasting blood samples were obtained both before and 6 weeks after the switch to measure serum lipid fractions, lipoprotein(a), C‐reactive protein, and homocysteine. A comparator group of 16 healthy subjects underwent the same serial studies.
Results
In the epilepsy patients, switch from either phenytoin or carbamazepine produced significant declines in total cholesterol (−24.8mg/dl), atherogenic (non–high‐density lipoprotein) cholesterol (−19.9mg/dl), triglycerides (−47.1mg/dl) (all p < 0.0001), and C‐reactive protein (−31.4%; p = 0.027). Patients who stopped taking carbamazepine also had a 31.2% decline in lipoprotein(a) level (p = 0.0004), whereas those taken off phenytoin had a decrease in homocysteine level (−1.7μmol/L; p = 0.005). All of these changes were significant when compared with those seen in healthy subjects (p < 0.05). Results were similar whether patients were switched to lamotrigine or levetiracetam.
Interpretation
Switching epilepsy patients from the enzyme‐inducers carbamazepine or phenytoin to the noninducing drugs levetiracetam or lamotrigine produces rapid and clinically significant amelioration in several serological markers of vascular risk. These findings suggest that phenytoin and carbamazepine may substantially increase the risk for cardiovascular and cerebrovascular disease. Ann Neurol 2009;65:448–456
Summary
Objective
Outcomes after changing antiepileptic drugs (AEDs) have largely been studied in single cohort series. We recently reported the first study to examine this question in a controlled ...manner. Here we expand on these results by using a matched, prospective methodology applied to both uncontrolled and well‐controlled patients taking any AED.
Methods
We reviewed all outpatient notes over a 9‐month period and identified patients with focal epilepsy who were on monotherapy. We classified those who switched AEDs as case patients, with those remaining on the same drug serving as controls. We matched cases with controls for seizure status (seizure‐free in the preceding 6 months or not), current AED, and number of failed AEDs. We subsequently assessed outcome 6 months later.
Results
Seizure‐free patients who switched drug (n = 12) had a 16.7% rate of seizure recurrence at 6 months, compared to 2.8% among controls remaining on the same drug (n = 36, p = 0.11). There was a 37% remission rate among uncontrolled patients who switched drug compared to 55.6% among controls (n = 27 per group, p = 0.18). Uncontrolled patients who had previously tried more than one AED were somewhat less likely to enter remission (p = 0.057). Neither AED mechanism of action nor change in dosage impacted outcome.
Significance
Herein we provide further estimation of the modest risk (~14%) associated with switching AEDs in patients in remission compared to being maintained on the same regimen. Uncontrolled patients were no more likely to enter remission after a drug switch than they were after remaining on the same drug, suggesting that spontaneous changes in disease state, and not drug response, underlie remission in this population.
Adult Focal Epilepsies Skidmore, Christopher T
Continuum (Minneapolis, Minn.)
22, Issue:
1 Epilepsy
Journal Article
Focal epilepsy is the most common type of epilepsy in adulthood. This article discusses the seizure symptomatology, EEG findings, and imaging findings of the various forms of focal epilepsy. The ...majority of the article focuses on temporal and frontal lobe epilepsy as these represent the majority of focal epilepsies.
While significant overlap exists in the clinical symptomatology of the focal epilepsies, detailed seizure descriptions can often provide useful clinical evidence to help establish an accurate diagnosis. EEG and MRI continue to serve as the main diagnostic tools for the diagnosis of focal epilepsy.
The various forms of focal epilepsy generate seizure presentations that are dependent on the anatomic structures that are involved in the seizure. By understanding the symptoms typically generated in each region of the brain, a better understanding of the possible seizure localizations can be made. Most forms of epilepsy have clear changes on EEG that permit accurate localization, but several pitfalls exist, which are discussed in this article. Imaging has revolutionized our ability to accurately identify lesions associated with epilepsy and increased our ability to localize seizures in the brain.
Summary
Purpose: Studies of seizure outcome in patients undergoing serial antiepileptic drug trials have all been uncontrolled, with no account made for the spontaneous changes in disease state that ...could confound the elucidation of drug effects. In addition, no study has ever looked at outcome following antiepileptic drug switch in seizure‐free patients, despite the fact that this is done routinely in clinical practice. We aimed to address both of these issues using a matched case‐cohort design.
Methods: We followed patients taking phenytoin or carbamazepine in monotherapy for focal epilepsy who were being crossed over to a newer agent as part of studies on the metabolic effects of anticonvulsant therapy. Many had been seizure‐free but were being switched nonetheless due to side effects or concerns about long‐term adverse consequences. Each patient was matched with two controls of the same seizure status who were taking anticonvulsant monotherapy and whose drug was not switched. Seizure freedom over the ensuing 6 months was the primary end point.
Key Findings: There were 43 cases and 86 matched controls. Twenty‐three patients (cases) had been seizure‐free on their old drug; 5 (21.7%) had seizure recurrence after drug switch compared to 2 (4.3%) of 46 matched controls. Twenty patients (cases) were having seizures on their old drug; 6 (30%) entered remission after drug switch, compared to 8 of 40 matched controls (20%). The two groups differed at baseline in number of anticonvulsants previously failed, which was the most important factor for prognosis. After statistical adjustment to account for this, seizure‐free patients had 6.53 times higher odds of seizure recurrence if switched to a new drug (95% confidence interval CI 1.02–61.19; p = 0.06). Non–seizure‐free patients had 1.66 times higher odds of remission if they remained on the same drug compared to switching, although this was not significant (95% CI 0.36–8.42; p = 0.532). Neither dose changes, nor drug mechanism, nor duration of seizure freedom had any bearing upon the results.
Significance: Although the large majority of seizure‐free patients remain so when switched to another agent, about one sixth have a recurrence attributable to the change. Conversely, our study design provides the first evidence to suggest that most improvements in drug‐resistant patients are likely due to spontaneous remissions, not new drug introductions. These findings have conflicting implications for two competing models of comparative antiepileptic drug efficacy, which will require further study to elaborate.
Anterior temporal lobectomy (ATL) is commonly adopted to control medically intractable temporal lobe epilepsy (TLE). Depending on the side of resection, the degree to which Wallerian degeneration and ...adaptive plasticity occur after ATL has important implications for understanding cognitive and clinical outcome. We obtained diffusion tensor imaging from 24 TLE patients (12 left) before and after surgery, and 12 matched controls at comparable time intervals. Voxel-based analyses were performed on fractional anisotropy (FA) before and after surgery. Areas with postoperative FA increase were further investigated to distinguish between genuine plasticity and processes related to the degeneration of crossing fibers. Before surgery, both patient groups showed bilateral reduced FA in numerous tracts, but left TLE patients showed more extensive effects, including language tracts in the contralateral hemisphere (superior longitudinal fasciculus and uncinate). After surgery, FA decreased ipsilaterally in both ATL groups, affecting the fornix, uncinate, stria terminalis, and corpus callosum. FA increased ipsilaterally along the superior corona radiata in both left and right ATL groups, exceeding normal FA values. In these clusters, the mode of anisotropy increased as well, confirming fiber degeneration in an area with crossing fibers. In left ATL patients, pre-existing low FA values in right superior longitudinal and uncinate fasciculi normalized after surgery, while MO values did not change. Preoperative verbal fluency correlated with FA values in all areas that later increased FA in left TLE patients, but postoperative verbal fluency correlated only with FA of the right superior longitudinal fasciculus. Our results demonstrate that genuine reorganization occurs in non-dominant language tracts after dominant hemisphere resection, a process that may help implement the inter-hemispheric shift of language activation found in fMRI studies. The results indicate that left TLE patients, despite showing more initial white matter damage, have the potential for greater adaptive changes postoperatively than right TLE patients.
Frontal lobe seizures Bagla, Ritu; Skidmore, Christopher T
The Neurologist (Baltimore, Md.)
17, Issue:
3
Journal Article
Peer reviewed
Frontal lobe epilepsy is the second most common localization-related or focal epilepsy. Frontal lobe seizures are challenging to diagnose as the clinical manifestations are diverse due to the ...complexity and variability of the patterns of epileptic discharges, and the scalp electroencephalograph (EEG) can often be normal or misleading. This review focuses on the clinical and EEG features of seizures arising from the frontal lobe.
The clinical manifestations in patients with frontal lobe epilepsy are varied. Frontal lobe seizures can be divided into perirolandic, supplementary sensorimotor area, dorsolateral, orbitofrontal, anterior frontopolar, opercular, and cingulate types. Seizures originating from the perirolandic and supplementary sensorimotor areas are clinically distinct, characterized by motor activity or asymmetric tonic posturing with preserved awareness. Seizures arising from dorsolateral, orbitofrontal, frontopolar, and cingulate areas are not as well characterized and have more variable clinical manifestations. Scalp EEG recording is sometimes helpful in localization but is usually normal or misleading in frontal lobe epilepsy. The treatment is similar to other localization-related or focal epilepsies. Medications are the first line of therapy, and surgery is considered for patients who fail to respond to medications. The surgical outcome in frontal lobe resections is less favorable than in anterior temporal lobectomies due to the challenge in locating the epileptogenic zone and the presence of functional areas (eloquent cortex) that can limit the resection.
Frontal lobe seizures are characterized by diverse behavioral manifestations. Only a few well-described frontal lobe syndromes exist. The variety of clinical manifestations reflects both the varying sites of seizure origin and propagation routes that seizures may take. Although this review provides a framework for the understanding of these seizures, one should remain cautious in diagnosing seizure localization based on clinical or EEG description. Only a few patients have well-described syndromes and can be diagnosed with confidence. For most patients, new diagnostic methods and genetic testing may help improve our ability to diagnose and treat the conditions discussed in this study.
•It is the first reported cohort of pregnancy outcomes in women concurrently treated with RNS System.•No major congenital malformation in the offspring of 10 WWE treated with the RNS System.•One ...child from WWE with advanced maternal age and bicornuate uterus had a minor congenital anomaly.•Research highlighting the data of RNS system use during pregnancy is limited.
To study the pregnancy outcomes, including obstetric complications and fetal outcomes, in pregnant women with epilepsy (WWE) treated with direct brain–responsive neurostimulation (RNS System).
Retrospective review of obstetric outcomes and fetal outcomes in WWE treated with the RNS System at nine comprehensive epilepsy centers in the United States from 2014–2020. In addition, changes in seizure frequency, anti-seizure medications, and RNS System setting adjustments during pregnancy were investigated.
A total of 10 subjects and 14 pregnancies were identified. The mean age at conception was 30.6 ± 4.3 years old. The mean age at implantation was 29.8 ± 4.4 years old. The mean stimulation charge densities ranged from 1.0 to 3.0 μC/cm2 during pregnancy. Obstetric complications included recurrent miscarriage (1 patient), cesarean section (3 patients) due to preeclampsia, non-reassuring fetal heart rate tracing or prolonged labor, preterm birth (1 patient), and preeclampsia (1 patient). No still birth, gestational hypertension, gestational diabetes, eclampsia, or maternal mortality were observed. No RNS System-exposed pregnancies had major congenital malformations. One offspring had a minor congenital anomaly of cryptorchidism in a pregnancy complicated with risk factors of advanced maternal age and bicornuate uterus.
The present study is the first report of RNS System-exposed pregnancies in WWE to date. No major congenital malformations were identified. All of the obstetric complications were within the expected range of those in WWE based on previously published data. The sample size of our study is small, so accumulation of additional cases will further help depict the safety profile of treatment with the RNS System during pregnancy.
Abstract Background Prior studies have shown that switching patients from inducing antiepileptic drugs (AEDs) to lamotrigine, levetiracetam, or topiramate reduces serum lipids and C-reactive protein ...(CRP). These studies were all of short duration, and some drugs, such as zonisamide, have not been investigated. Methods We recruited 41 patients taking phenytoin or carbamazepine who were being switched to zonisamide, lamotrigine, or levetiracetam. We measured serum lipids and CRP before the switch, > 6 weeks after, and > 6 months after. An untreated control group (n = 14) underwent similar measurement. We combined these data with those of our previous investigation (n = 34 patients and 16 controls) of a very similar design. Results There were no differences in outcome measures between the two inducing AEDs nor among the three noninducing AEDs. Total cholesterol (TC), atherogenic lipids, and CRP were higher under inducer treatment than in controls. All measures were elevated under inducer treatment relative to noninducer treatment, including TC (24 mg/dL higher, 95% CI: 17.5–29.9, p < 0.001) and CRP (72% higher, 95% CI: 41%–111%, p < 0.001). The difference between drug treatments was clinically meaningful for atherogenic lipids (16%, 95% CI: 11%–20%, p < 0.001) but small for high-density lipoprotein cholesterol (5%, 95% CI: 1%–9%, p < 0.05). All measures were stable between 6 weeks and 6 months after drug switch. Conclusions We demonstrate that switching from inducing to noninducing AEDs produces an enduring reduction in serum lipids and CRP. These results provide further evidence that inducing AEDs may be associated with elevated vascular disease risk. These are the first vascular risk marker data in patients taking zonisamide, which shows a profile similar to that of other noninducing AEDs.
Abstract Enzyme-inducing antiepileptic drugs (AEDs) produce many alterations in metabolism, including vitamin levels. Whether they produce clinically relevant deficiency of B vitamins has rarely been ...assessed. We obtained B‐vitamin levels in patients who were being converted from an inducing AED (phenytoin or carbamazepine) to a non-inducing AED (levetiracetam, lamotrigine, or topiramate), with measurements both before and ≥ 6 weeks after the switch. A group of normal subjects underwent the same studies. Neither folate nor B12 deficiency was seen in any patient. Vitamin B6 deficiency was found in 16/33 patients (48%) taking inducers, compared to 1/11 controls (9%; p = 0.031). After switch to non-inducers, only 7 patients (21%) were B6 deficient (p = 0.027). The incidence of deficiency was similar regardless of which inducing or non-inducing AED was being taken. Our findings demonstrate that treatment with inducing AEDs commonly causes pyridoxine deficiency, often severe. This could conceivably contribute to the polyneuropathy sometimes attributed to older AEDs, as well as other chronic heath difficulties.
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