Seizure outcome after switching antiepileptic drugs: A matched, prospective study.

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

Long-term effect of antiepileptic drug switch on serum lipids and C-reactive protein.

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, \u3e6weeks after, and \u3e6months 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 (24mg/dL higher, 95% CI: 17.5-29.9, p 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

A case of acute myeloid leukemia with promyelocytic features characterized by expression of a novel RARG-CPSF6 fusion

Key Points Novel RARG-CPSF6 fusion in an AML case with promyelocytic features and no evidence of PML-RARA or X-RARA fusion. Gene fusions involving RARG can initiate AML with promyelocytic morphological features.</jats:p

Conversion from enzyme-inducing antiepileptic drugs to topiramate: effects on lipids and C-reactive protein.

PURPOSE: We previously demonstrated that converting patients from the enzyme-inducers phenytoin or carbamazepine to the non-inducers levetiracetam or lamotrigine reduces serum lipids and C-reactive protein (CRP). We sought to determine if the same changes would occur when patients were switched to topiramate, which has shown some evidence of enzyme induction at high doses. We also examined the effects of drug switch on low-density lipoprotein (LDL) particle concentration. METHODS: We converted 13 patients from phenytoin or carbamazepine monotherapy to topiramate monotherapy (most at doses of 100-150 mg/day). Fasting lipids, including LDL particle concentration, and CRP were obtained before and ≥6 weeks after the switch. A group of normal subjects had the same serial serologic measurements to serve as controls. RESULTS: Conversion from inducers to topiramate resulted in a -35 mg/dL decline in total cholesterol (p=0.033), with significant decreases in all cholesterol fractions, triglycerides, and LDL particle concentration (p≤0.03 for all), as well as a decrease of over 50% in serum CRP (p CONCLUSIONS: Changes seen when inducer-treated patients are converted to TPM closely mimic those seen when inducer-treated patients are converted to lamotrigine or levetiracetam. These findings provide evidence that CYP450 induction elevates CRP and serum lipids, including LDL particles, and that these effects are reversible upon deinduction. Low-dose TPM appears not to induce the enzymes involved in cholesterol synthesis

Functional connectivity evidence of cortico-cortico inhibition in temporal lobe epilepsy.

Epileptic seizures can initiate a neural circuit and lead to aberrant neural communication with brain areas outside the epileptogenic region. We focus on interictal activity in focal temporal lobe epilepsy and evaluate functional connectivity (FC) differences that emerge as function of bilateral versus strictly unilateral epileptiform activity. We assess the strength of FC at rest between the ictal and non-ictal temporal lobes, in addition to whole brain connectivity with the ictal temporal lobe. Results revealed strong connectivity between the temporal lobes for both patient groups, but this did not vary as a function of unilateral versus bilateral interictal status. Both the left and right unilateral temporal lobe groups showed significant anti-correlated activity in regions outside the epileptogenic temporal lobe, primarily involving the contralateral (non-ictal/non-pathologic) hemisphere, with precuneus involvement prominent. The bilateral groups did not show this contralateral anti-correlated activity. This anti-correlated connectivity may represent a form of protective and adaptive inhibition, helping to constrain epileptiform activity to the pathologic temporal lobe. The absence of this activity in the bilateral groups may be indicative of flawed inhibitory mechanisms, helping to explain their more widespread epileptiform activity. Our data suggest that the location and build up of epilepsy networks in the brain are not truly random, and are not limited to the formation of strictly epileptogenic networks. Functional networks may develop to take advantage of the regulatory function of structures such as the precuneus to instantiate an anti-correlated network, generating protective cortico-cortico inhibition for the purpose of limiting seizure spread or epileptogenesis

Temporal lobe epilepsy and surgery selectively alter the dorsal, not the ventral, default-mode network.

The default-mode network (DMN) is a major resting-state network. It can be divided in two distinct networks: one is composed of dorsal and anterior regions [referred to as the dorsal DMN (dDMN)], while the other involves the more posterior regions [referred to as the ventral DMN (vDMN)]. To date, no studies have investigated the potentially distinct impact of temporal lobe epilepsy (TLE) on these networks. In this context, we explored the effect of TLE and anterior temporal lobectomy (ATL) on the dDMN and vDMN. We utilized two resting-state fMRI sessions from left, right TLE patients (pre-/post-surgery) and normal controls (sessions 1/2). Using independent component analysis, we identified the two networks. We then evaluated for differences in spatial extent for each network between the groups, and across the scanning sessions. The results revealed that, pre-surgery, the dDMN showed larger differences between the three groups than the vDMN, and more particularly between right and left TLE than between the TLE patients and controls. In terms of change post-surgery, in both TLE groups, the dDMN also demonstrated larger changes than the vDMN. For the vDMN, the only changes involved the resected temporal lobe for each ATL group. For the dDMN, the left ATL group showed post-surgical increases in several regions outside the ictal temporal lobe. In contrast, the right ATL group displayed a large reduction in the frontal cortex. The results highlight that the two DMNs are not impacted by TLE and ATL in an equivalent fashion. Importantly, the dDMN was the more affected, with right ATL having a more deleterious effects than left ATL. We are the first to highlight that the dDMN more strongly bears the negative impact of TLE than the vDMN, suggesting there is an interaction between the side of pathology and DM sub-network activity. Our findings have implications for understanding the impact TLE and subsequent ATL on the functions implemented by the distinct DMNs

Where do you stand?: An exploration of perspectives toward feet, foot health, and footwear using innovative digital methods

Background: The cost of losing foot health is significant to the person, healthcare systems, and economy, with diabetes related foot health issues alone costing over £1 billion annually in the UK. Yet many foot health problems are preventable through alternative health behaviour. It is therefore important to understand how feet, foot health and footwear are conceptualised to gain understanding about how these might influence foot health behaviour and inform health messages that seek to protect or improve foot health through altered health behaviour. This research seeks to explore attitudes and beliefs and identify phenomena that may act as barriers or motivators to the proactive self-management of foot health, Methods Public conversations involving 2,699 expressions related to feet, footwear or foot health on Facebook, Twitter, and Instagram were extracted. Conversations on Facebook and Twitter were scraped with NVivo’s NCapture plugin whereby data is extracted and downloaded to NVivo. Extracted files were uploaded to the Big Content Machine (software developed at the University of Salford) which facilitated the search for keywords ‘foot’, ‘feet’, ‘footwear’, ‘shoe’, and ‘shoes’. Instagram was scraped by hand. Data was analysed using a Thematic Analysis approach. Results Three themes were identified; 1) connections and disconnections derived from social and cultural constructs, 2) phenomena beyond attitudes and beliefs that relate to symbolic representations and the impact when foot health is lost, and 3) phenomena relating to SoMe as a conduit for the exploration of attitudes and beliefs. Conclusions This novel research exemplifies complex and sometimes incongruous perspectives about feet including their value for what they facilitate, contrasted with negative feelings about the negative impact that can have aesthetically when feet work hard. Sometimes feet were devalued, with expressions of disgust, disconnection, and ridicule. The importance of contextual, social, and cultural phenomena with implications for optimising foot health messages. Knowledge gaps including factors related to children’s foot health and development, and how to treat foot health problems. The power of communities with shared experience to influence decisions, theories, and behaviour about foot health was also revealed. While people do talk about feet in some social contexts, it is not always in a way that promotes overt, positive foot health behaviour. Finally, this research demonstrates the benefit of exploring perspectives in uncontrived settings and illuminates the potential utility of SoMe as a vehicle to promote foot health self-management behaviour that is responsive to the social and demographic variances of engagers who inhabit those spaces