•Critically illness polyneuropathy/myopathy (CIN/CIM) was more prevalent in COVID-19 ICU patients with severe illness.•Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) ...levels were higher in the CIN/CIM group and GFAp correlated with motor nerve amplitudes.•COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care.
The aim was to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in coronavirus disease 2019 (COVID-19) patients with intensive care unit acquired weakness (ICUAW).
An observational ICU cohort study including adult patients admitted to the ICU at Uppsala University Hospital, Uppsala, Sweden, from March 13th to June 8th 2020. We compared the clinical, electrophysiological and plasma biomarker data between COVID-19 patients who developed CIN/CIM and those who did not. Electrophysiological characteristics were also compared between COVID-19 and non-COVID-19 ICU patients.
111 COVID-19 patients were included, 11 of whom developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%) compared with a non-COVID-19 cohort (0%, p = 0.008). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group compared with those that did not develop CIN/CIM (both p = 0.001) and correlated with nerve amplitudes.
CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness.
COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care, suggesting their potential as predictive biomarkers for CIN/CIM.
•We studied discontinuation of first AED in patients with poststroke epilepsy.•Carbamazepine was used as reference and data was collected until the end of 2014.•5-year retention rates were higher for ...lamotrigine (LGT) and levetiracetam (LEV).•LTG and LEV had lower risks of discontinuation in crude and adjusted Cox models.•These findings agree with short-term tolerability data from small RCTs.
To describe the retention rates of first antiepileptic drugs (AEDs) in patients with poststroke epilepsy on a nationwide scale.
The Swedish Stroke Register, which has 94% coverage and high-resolution data on stroke, comorbidities, and disability, was cross-referenced to the National Patient Register, Drug Register, and Cause-of-Death Register. Patients with onset of AED-treated epilepsy after stroke in 2005–2010 were included. An algorithm based on prescription renewal intervals was used to analyze treatment data until the end of 2014.
A total of 4991 patients were included. First AEDs analyzed were carbamazepine (n = 2373), valproic acid (n = 943), levetiracetam (n = 555), lamotrigine (n = 519), phenytoin (n = 176), and oxcarbazepine (n = 89). The five-year retention rate was highest for lamotrigine (75%, 95%CI:70.4–79.4), followed by levetiracetam (69%, 95%CI:62.9–74.3), oxcarbazepine (68%, 95%CI:55.2–79.8), valproic acid (62%, 95%CI:57.8–66.4), carbamazepine (60%, 95%CI:57.6–62.4), and phenytoin (55%, 95%CI:45.2–64.0). There were minor differences in baseline characteristics with low levels of disability being slightly more common in patients treated with lamotrigine and levetiracetam. Atrial fibrillation and hypertension were more common in patients treated with levetiracetam, and atrial fibrillation was less common in patients treated with carbamazepine. In a Cox model adjusted for baseline characteristics, the risk of discontinuation was lower for lamotrigine (HR 0.53, 95%CI:0.43-0.67) and levetiracetam (HR 0.75, 95%CI:0.60-0.94) when compared to carbamazepine.
Lamotrigine and levetiracetam have higher retention rates than carbamazepine in poststroke epilepsy. This is in agreement with existing small RCTs in this patient group.
The risk of death is increased for persons with epilepsy. The literature on causes of death in epilepsy is based mainly on cohorts with epilepsy of mixed aetiologies. For clinical purposes and ...improved understanding of mortality in different epilepsies, more information is needed on mortality in epilepsies of specific causes. In poststroke epilepsy (PSE), seizures occur in a setting of vascular disease and high mortality rates. The extent to which epilepsy contributes to mortality in this patient group is poorly understood. We therefore aimed to describe causes of death (COD) in PSE on a national scale. A previously identified cohort of 7740 patients with epilepsy or seizures after a stroke in 2005-2010 was investigated. A total of 4167 deaths occurred before the end of 2014. The standardized mortality ratio for the study cohort was 3.56 (95% CI: 3.45-3.67). The main underlying causes of death were disorders of the circulatory system (60%) followed by neoplasms (12%). Diseases of the nervous system were the sixth leading underlying COD (3%), and epilepsy or status epilepticus was considered the underlying COD in approximately a similar proportion of cases as neurodegenerative disorders (0.9% and 1.1%, respectively). Epilepsy was considered a contributing COD in 14% of cases. Our findings highlight the importance of optimal management of vascular morbidity in patients with PSE. The large proportion of patients with epilepsy as a contributing COD indicate the need of high ambitions also regarding the management of seizures in patients with PSE.
Highlights • Coma is the most common neurological symptom related to hypoglycemia. • Epileptic seizures in relation to hypoglycemia are rare. • In this study of a large number of patients with ...hypoglycemia, a notably low frequency of seizures was noticed. This indicates that the risk of seizures in association with low blood glucose levels seems to be low.
Summary
Objective
The International League Against Epilepsy (ILAE) Epilepsy Guidelines Task Force, composed of 14 international members, was established in 2011 to identify, using systematic review ...methodology, international epilepsy clinical care guidelines, assess their quality, and determine gaps in areas of need of development.
Methods
A systematic review of the literature (1985–2014) was performed in six electronic databases (e.g. Medline, Embase) using a broad search strategy without initial limits to language or study design. Six gray literature databases (e.g., American Academy of Neurology AAN, ILAE) were also searched to minimize publication bias. Two independent reviewers screened s, reviewed full text articles, and performed data ion. Descriptive statistics and a meta‐analysis were generated.
Results
The search identified 10,926 s. Of the 410 articles selected for full text review, 63 met our eligibility criteria for a guideline. Of those included, 54 were in English and 9 were in other languages (French, Spanish, and Italian). Of all guidelines, 29% did not specify the target age groups, 27% were focused on adults, 22% included only children, and 6% specifically addressed issues related to women with epilepsy. Guidelines included in the review were most often aimed at guiding clinical practice for status epilepticus (n = 7), first seizure (n = 6), drug‐resistant epilepsy (n = 5), and febrile seizures (n = 4), among others. Most of the guidelines were therapeutic (n = 35) or diagnostic (n = 16) in nature. The quality of the guidelines using a 1–7 point scale (7 = highest) varied and was moderate overall (mean = 4.99 ± 1.05 SD).
Significance
We identified substantial gaps in topics (e.g., epilepsy in the elderly) and there was considerable heterogeneity in methodologic quality. The findings should offer a valuable resource for health professionals caring for people with epilepsy, since they will help guide the prioritization, development, and dissemination of future epilepsy‐related guidelines.
Background
In preclinical studies, the positron emission tomography (PET) imaging with
11
CUCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic ...density. This paper reports the first-in-human
11
CUCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding.
Results
Twelve healthy subjects underwent 90-min baseline
11
CUCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg). Our results indicated abundant
11
CUCB-A brain uptake across all cortical regions, with slow elimination. Kinetic modelling of
11
CUCB-A PET using various compartment models suggested that the irreversible two-tissue compartment model best describes the kinetics of the radioactive tracer. Accordingly, the Patlak graphical analysis was used to simplify the analysis. The estimated SV2A occupancy determined by the Lassen plot was around 66%. Significant specific binding at baseline and comparable binding reduction as grey matter precludes the use of centrum semiovale as reference tissue.
Conclusions
11
CUCB-A PET imaging enables quantifying SV2A in vivo. However, its slow kinetics require a long scan duration, which is impractical with the short half-life of carbon-11. Consequently, the slow kinetics and complicated quantification methods may restrict its use in humans.
Introduction
Poststroke epilepsy (PSE) is the most common form of acquired epilepsy after middle age. The primary aim of this study was to study the impact of PSE on prognosis. A secondary aim was to ...validate recent findings from smaller studies on the risk of developing PSE on a nationwide scale.
Patients and methods
We performed a nationwide cohort study based on comprehensive national registries and included patients without a prior epilepsy diagnosis surviving more than 2 months after stroke, identified by the Swedish Stroke Register (Riksstroke) and linked to the National Patient Register and Cause of Death Register. Cox proportional time-updated hazard model was used to assess the risk of death, with or without multivariable adjustment for possible confounders, and multiple Cox regression was used to examine associations between PSE and clinical characteristics.
Results
In 106,455 patients, PSE (defined as a seizure diagnosis more than 7 days after stroke) was detected in 7.3%, with lower cumulative incidence after ischemic stroke (6.4%) than after intracerebral haemorrhage (12.4%). Stroke severity, intracerebral haemorrhage and young age were associated with a risk of PSE. The risk of death was increased in patients with PSE (hazard ratio: 1.68, 95% confidence interval: 1.25–1.53). Also with adjustments for age, comorbidities and stroke severity, an increased risk of death associated with PSE remained.
Discussion
Studies are needed on potential causes of increased mortality in PSE, such as a direct seizure-related mortality, less ambitious secondary stroke prophylaxis or rehabilitation, or impact of antiepileptic drugs on cardiovascular risk.
Objectives
Immunotherapy in addition to antiepileptic drugs can improve seizure freedom rates in autoimmune epilepsy, highlighting the importance of early diagnosis. A diagnosis of autoimmune ...epilepsy can be supported by presence of serum antibodies to neuronal antigens. We asked how often neuronal antibodies are found in the serum of unselected adult patients with new‐onset seizures and whether such testing could improve detection of autoimmune epilepsy.
Material and Methods
We included 44 patients over the age of 25 presenting after at least one unprovoked seizure to the Neurology Clinic at Sahlgrenska University Hospital, Gothenburg, Sweden. The median time between the first‐ever seizure in life and the serum sampling was 50 days (range 22–11,000). Antibody testing in serum was performed according to the manufacturer's instructions. The patients were followed for at least 1 year.
Results
Epilepsy could be diagnosed already at the first visit in 21/44 patients (47.7%). Two patients (4.5%) were positive for neuronal antibodies: one against contactin‐associated protein 2 (CASPR‐2) and one against glutamate acid decarboxylase (GAD). Three patients (6.7%) displayed very weak immunoreactivity that was deemed clinically insignificant. One of the antibody‐positive patients had only a single seizure. The other had a focal cortical dysplasia and was seizure‐free on levetiracetam. None of the five patients with antibodies or immunoreactivity displayed any feature of autoimmune epilepsy.
Conclusions
We conclude that indiscriminate testing in patients presenting to a first seizure clinic with new‐onset seizures or epilepsy is unlikely to improve detection of autoimmune epilepsy.
We asked how often neuronal antibodies are found in the serum of unselected adult patients with new‐onset seizures and whether such testing could improve detection of autoimmune epilepsy. Two patients (4.5%) were positive for neuronal antibodies and three had weak immunoreactivity deemed clinically insignificant, none had clinical features of autoimmune epilepsy. We conclude that indiscriminate testing in patients presenting to a first‐seizure clinic with new‐onset seizures or epilepsy is unlikely to improve detection of autoimmune epilepsy.
Inflammatory processes may provoke epileptic seizures and seizures may promote an immune reaction. Hence, the systemic immune reaction is a tempting diagnostic and prognostic marker in epilepsy. We ...explored the immune response before and after epileptic and psychogenic non-epileptic seizures (PNES). Serum samples collected from patients with videoEEG-verified temporal or frontal lobe epilepsy (TLE or FLE) or TLE + PNES showed increased interleukin-6 (IL-6) levels in between seizures (interictally), compared to controls. Patients with PNES had no increase in IL-6. The IL-6 levels increased transiently even further within hours after a seizure (postictally) in TLE but not in FLE patients. The postictal to interictal ratio of additionally five immune factors were also increased in TLE patients only. We conclude that immune factors have the potential to be future biomarkers for epileptic seizures and that the heterogeneity among different epileptic and non-epileptic seizures may be disclosed in peripheral blood sampling independent of co-morbidities.
•Elevated IL-6 levels in serum in patients with temporal and frontal lobe epilepsy•Altered postictal-interictal ratio of immune factors in serum after temporal but not frontal lobe seizures•No change in IL-6 levels in serum in patients with psychogenic non-epileptic seizures
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