Epilepsy surgery, particularly dominant temporal lobe resection, poses a significant risk of post-surgical language decline. There is considerable heterogeneity in the language assessment protocols employed across epilepsy surgery centers. This in turn is reflected in the observed variability in the incidence of language decline reported in the literature. We systematically surveyed cognitive outcome literature to critically appraise the nature and frequency of language assessment in order to establish the parameters of the existing evidence base. We found that confrontation naming was the most frequently used paradigm to assess language function (96%), followed by verbal fluency (47%) and language comprehension (13%). Over 75% of studies reported outcomes within the first two years of surgery, and close to 50% used reliable change index (RCI) to measure pre–post change in function, which is considered to be the gold standard. The evidence base is currently saturated with short-term post-surgical language outcomes assessed at single-word level. Future studies employing comprehensive language assessment, longer follow-up intervals, and designs comparing different metrics of pre–post change in function are needed.
Objective: Infantile and epileptic spasms syndrome (IESS) is a developmental and epileptic encephalopathy manifesting with epileptic spasms and poor neurodevelopmental outcomes. There is an urgent need for the development of more effective and tolerated therapies. The multiple-hit model of IESS due to structural etiology has been optimized for the screening of treatments for spasms. Here, we test in this model the efficacy and tolerability of clinically available treatments (6α-methylprednisolone, topiramate), as well as of the following investigative compounds: the anti-inflammatory/immunomodulatory compounds fingolimod and sivelestat, and the insulin-like growth factor tripeptide IGF-1(1-3).
Methods: Postnatal day 3 (PN3) male Sprague-Dawley rats were induced by right intracerebroventricular doxorubicin and right intracortical lipopolysaccharide infusions and underwent daily assessments of body weights, motor and developmental milestones, and intermittent monitoring for spasms. Blood glucose was measured in selected drugs (6α-methylprednisolone, IGF-1[1-3]). Blinded, vehicle-controlled, dose and time response experiments were conducted. Drugs were administered as single intraperitoneal injections after spasms onset, except for IGF-1(1-3), which was tested as daily injections given from PN4 to PN10. Hourly spasms frequencies, raw or normalized to pretreatment frequencies, were determined and analyzed using a mixed linear model considering repeated measures.
Results: Spasms frequency reduction was more consistent with the glucocorticosteroid 6α-methylprednisolone than topiramate. Fingolimod reduced spasms during the first 2 h whereas the sivelestat had longer lasting effects in reducing spasm rates during the first 5 h. Repeat administration of daily IGF-1(1-3) between PN4 and PN10 had no effect on raw frequencies of spasms and only reduced the normalized frequencies during the third treatment day (PN6). None of the treatments increased the spasm-freedom rates or achieved >50% reduction in spasm frequencies.
Significance: Our study further supports that the multiple-hit model is a model of drug-resistant spasms and suggests that anti-inflammatory/immunomodulatory treatments like fingolimod and sivelestat may have rapid effects on reducing spasms in the model.
Plain language summary: Infantile and epileptic spasms syndrome (IESS) manifests with epileptic spasms and negatively affects the infants' development due to cognitive and behavioral problems. We have optimized the multiple-hit rat model of IESS to screen for new therapies and present here an overview of the model, which models drug-resistant IESS due to structural etiology. We also present new data on the acute effects of five drugs on spasms and a comparative assessment of all the treatments tested in this model for effects and tolerability on spasms, developmental deficits, adul
Driving is consistently reported as an important goal for people with epilepsy. We sought to determine the proportion of people with drug-resistant epilepsy (DRE) who became medically fit to drive after treatment with vagus nerve stimulation (VNS). We conducted a retrospective observational study of consecutive patients treated with VNS attending our neuromodulation clinic. We classified patients as either “VNS responders without additional intervention” or “VNS responders with additional intervention” and determined if patients were eligible to drive Group 1 vehicles (cars, motorcycles, and light work vehicles) under Irish Medical Fitness to Drive regulations. Among 87 patients treated with VNS for ≥12 months, 15 became medically eligible to drive: five were current drivers, three were learner drivers, and seven were eligible to drive based on their seizure control but were not driving for various reasons. Eleven were seizure-free, three had nondisabling focal seizures with preserved consciousness, and one had exclusive sleep-related seizures. Eleven were “VNS responders without additional intervention,” while four achieved eligibility after adding ASM or following subsequent epilepsy surgery, while VNS was still active. No patients reported driving-related accidents. ASM burden remained unchanged post-VNS. VNS was well tolerated, and no patients discontinued treatment. In this cohort, 17.2% of patients treated with VNS became eligible to drive, despite it being considered a palliative treatment. These findings highlight the potential role of neuromodulation in improving seizure control and promoting patient autonomy and independence.
This study investigated whether people with refractory epilepsy in Ireland could become eligible to drive after VNS treatment. In our single-center cohort, 17.2% of patients treated with VNS for at least 12 months were eligible to drive at last follow-up. Most achieved this without increasing their medication after VNS implantation. These findings suggest that VNS, often considered a palliative treatment, can help some patients regain independence through improved seizure control.
Epilepsy is primarily defined by the repetitive occurrence of seizures, but the full impact of seizures extends beyond these episodic events. Seizures themselves cause changes at the cellular, network, and systemic levels in individual patients with epilepsy and may contribute to the progressive nature of the disease in some patients. Seizures may have an impact on brain structure and function over time. There is also a high societal and economic burden associated with persistent seizures, including major impacts on quality of life, activities of daily living, and productivity. Therefore, seizure freedom with no or minimal side effects should be the key goal in the treatment of epilepsy, with the potential to reduce both disease progression and the societal and economic impacts of the disease. Physicians have a responsibility to address the key obstacles to early seizure freedom, including optimizing initial treatment strategies, minimizing treatment delays, overcoming therapeutic nihilism, and improving medication adherence.
Epilepsy involves repeated seizures which can cause changes in the brain over time and affect memory, thoughts, and everyday activities. Repeated seizures place a heavy burden on individuals, families, and society, affecting their quality of life, independence, and work. The main goal of epilepsy treatment should be the elimination of all seizures with few or no side effects. To achieve this, doctors should act quickly, choose the right treatments early, avoid treatment delays, and support patients in taking their medications.
Landau–Kleffner syndrome (LKS) is a rare epileptic syndrome causing language regression. In this preliminary study, we investigated the effects of simultaneous transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (rTMS) on LKS patients and the underlying mechanism based on magnetoencephalography (MEG) network analysis. Three LKS patients were included, all receiving daily stimulation for 15 days in 3 weeks, with MEG data collected to determine stimulation target and measure functional connectivity through normalized phase transfer entropy (PTE). The primary clinical outcome was measured through the Peabody Picture Vocabulary Test. Two patients with clustered spike dipoles in the right inferior parietal lobe (IPL) showed profound clinical improvement after stimulation. PTE analysis showed increased dorsal pathway information flow, mainly in the left hemisphere, and increased ventral pathway information flow in both hemispheres. This study preliminarily showed that tDCS-rTMS was safe to undergo and likely to improve language function in LKS patients. Stimulating the right IPL not only affects the right hemisphere language network but also profoundly affects the left hemisphere network that participates in language perception, processing, and understanding. The dynamic balance of the language network connections was reconstructed, which may be associated with improved language function in LKS.
Due to the lack of effective long-term treatment options, we investigated the effects of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (rTMS) on language function in Landau–Kleffner syndrome (LKS) patients and the possible therapeutic mechanism by magnetoencephalography network analysis. Three LKS patients were included. We found tDCS-rTMS improved language function without side effects in two of the patients whose stimulation target was the right inferior parietal lobe, possibly due to significantly enhanced information flow in bilateral language streams, indicating modulated language network connections. Thus, we preliminarily proved the safety and effectiveness of tDCS-rTMS and unveiled underlying network mechanisms.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：