Unsupervised clustering of a deeply phenotyped cohort of adults with idiopathic generalized epilepsy.

Objective: Idiopathic generalized epilepsy (IGE) in adults comprise juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic-clonic seizures alone (EGTCS), which are defined by their seizure types but also cover a broad endophenotype of symptoms. Controversy exists on whether adult IGE is a group of distinct diseases or a clinical spectrum of one disease. Here, we used a deeply phenotyped cohort to test the hypothesis that IGE comprises three distinct clinical entities.

Intensive treatment course to identify pseudoresistant epilepsy and expedite surgery referrals - A prospective intervention study.

Introduction: A significant proportion of patients do not achieve seizure freedom despite treatment attempts with two different anti-seizure medications (ASMs). A subset may not truly have drug-resistant epilepsy ("pseudoresistant"), while rapid referral of patients with genuine drug-resistant epilepsy to surgery is mandated. This study was designed to evaluate a structured and intensive treatment course with the objective of promptly identifying cases of pseudoresistance and accelerating the time to referral to epilepsy surgery.

Magnetic Resonance Imaging Signs of Idiopathic Intracranial Hypertension.

Importance: The magnetic resonance imaging (MRI) criteria currently used to diagnose idiopathic intracranial hypertension (IIH) are based on expert opinion and have limited accuracy. Additional neuroimaging signs have been proposed and used with contradictory results; thus, prospective evidence is needed to improve diagnostic accuracy.

Objective: To provide evidence-based, accurate MRI signs for IIH diagnosis.

NORSE seasonality may vary geographically in adults.

The mechanisms causing new onset refractory status epilepticus (NORSE) are often unknown. Recently, a seasonal variation with NORSE peaking during the summer was described in a mixed cohort of adults and children why we here studied the seasonal variation in a Danish status epilepticus (SE) cohort. This retrospective cohort study comprised SE patients aged ≥18 diagnosed and treated 2008-2017 at the Odense University Hospital.

Outcomes and Treatment Approaches for Super-Refractory Status Epilepticus: A Systematic Review and Meta-Analysis.

Importance: Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues or recurs 24 hours or more after the onset of anesthetic therapy or recurs on the reduction/withdrawal of anesthesia. Current clinical knowledge of the disease and optimal treatment approach is sparse.

Objective: To systematically assess clinical characteristics, causes, outcomes, prognostic factors, and treatment approaches for patients with SRSE.

Association of ictal imaging changes in status epilepticus and neurological deterioration.

Objective: In patients with status epilepticus (SE), the clinical significance of ictal changes on magnetic resonance imaging (MRI) is insufficiently understood. We here studied whether the presence of ictal MRI changes was associated with neurological deterioration at discharge.

Methods: The retrospective cohort comprised all identifiable patients treated at Odense University Hospital in the period 2008-2017.

[Treatment of status epilepticus in children and adults].

This review finds that, in children and adults with epilepsy, there are several treatment options. Multiple antiseizure medications are available and in case of drug-resistant epilepsy, a non-pharmacological approach is recommended, including epilepsy surgery, vagus nerve stimulation, or ketogenic diet treatment. The aim of the treatment is to avoid further seizures, but also to avoid negative cognitive, psychological, and social consequences of epilepsy.

Prediction of Long-term Survival After Status Epilepticus Using the ACD Score.

Importance: Early prediction of long-term mortality in status epilepticus is important given the high fatality rate in the years after diagnosis.

Objective: To improve prognostication of long-term mortality after status epilepticus diagnosis.

Design, Settings, And Participants: This retrospective, multicenter, multinational cohort study analyzed adult patients who were diagnosed with and treated for status epilepticus at university hospitals in Odense, Denmark, between January 1, 2008, and December 31, 2017, as well as in Oslo, Norway; Marburg, Germany; and Frankfurt, Germany.

Social outcome and psychiatric comorbidity of generalized epilepsies - A case-control study.

Objective: To investigate social outcome and psychiatric comorbidity of patients with idiopathic/genetic generalized epilepsies (IGEs) and its subtypes (epilepsy with generalized tonic-clonic seizures alone [EGTCS], juvenile absence epilepsy [JAE], and juvenile myoclonic epilepsy [JME]).

Methods: A cohort of 402 adult patients with IGE from the Danish island Funen was matched with 4020 randomly selected geography-, age-, and sex-matched controls via the Danish Civil Registration System. Based on register data, we compared social status measured by cohabitant status, educational attainment, income, affiliation to labor market, and psychiatric comorbidity.

Safety and feasibility of an intensive epilepsy nurse-based treatment course.

Purpose: To determine safety, feasibility and patient satisfaction of an epilepsy nurse-based treatment course with frequent contacts and changes of anti-epileptic treatment provided by supervised anti-epileptic drug (AED) prescribing epilepsy nurses.

Methods: Regular prescheduled clinical contacts with a neurologist to adjust AED treatment were largely substituted by on-demand contacts with epilepsy nurses with the delegated right to adapt AED within predefined limits. To secure safety, electronic medical files of patients with 6 or more contacts with epilepsy nurses were retrospectively analysed for clinical characteristics, safety measures and seizure frequency before/after the intensive treatment course and patients were asked to complete a questionnaire about treatment satisfaction.

Risk factors of paradoxical reactions to anti-seizure medication in genetic generalized epilepsy.

This study aimed at providing valid estimates for the risk of clinically relevant seizure aggravation by recommended anti-seizure medications in patients with Genetic Generalized Epilepsy (GGE). To this aim, treatment response, side effects and paradoxical reactions to anti-seizure treatment were retrospectively assessed in a near-population based cohort comprising 471 adult GGE patients. A total of 1046 treatment attempts were analyzed (lamotrigine: 351, valproic acid: 295, levetiracetam: 249, primidone/phenobarbital: 94, zonisamide: 57).

Transient epileptic amnesia diagnosed using long-term electroencephalography.

Transient epileptic amnesia (TEA) is a distinct syndrome affecting middle-aged persons without concurrent brain disease or disposition to epileptic seizures. Seizures are characterized by amnesia, usually lasting less than one hour, and interictal memory deficits that are common. Effective antiseizure treatment is usually rapid in patients with TEA, which underlines the need for prompt diagnosis.

Alternative lengthening of telomeres is the major telomere maintenance mechanism in astrocytoma with isocitrate dehydrogenase 1 mutation.

Purpose: Isocitrate dehydrogenase 1 (IDH1) mutations are associated with improved survival in gliomas. Depending on the IDH1 status, TERT promoter mutations affect prognosis. IDH1 mutations are associated with alpha-thalassemia/mental retardation syndrome X-linked (ATRX) mutations and alternative lengthening of telomeres (ALT), suggesting an interaction between IDH1 and telomeres.

Epidemiology-Based Mortality Score is Associated with Long-Term Mortality after Status Epilepticus.

Background/objective: Status epilepticus (SE) is a life-threatening condition with a high long-term mortality. The correct prediction of the individual patient's outcome is crucial for stratifying treatment. Status epilepticus severity score (STESS) and the epidemiology-based mortality score (EMSE) are well established for predicting in-hospital mortality; however, scores indicating long-term mortality are lacking.

Aberrant neuronal differentiation is common in glioma but is associated neither with epileptic seizures nor with better survival.

The mechanisms of glioma-associated seizures (GAS) have yet to be fully elucidated. Proneural subtype, isocitrate dehydrogenase 1 (IDH1) mutations, and epileptic seizures are closely associated suggesting that aberrant neuronal differentiation contributes to glioma-associated seizures. In a population-based cohort (n = 236), lack of stem cell marker expression (nestin, musashi) was significantly associated with IDH1 mutations and GAS at diagnosis.

Hormonal contraception is not associated with increased risk for seizures in the general population: results from a cohort study using The Health Improvement Network.

Purpose: Endogenous human gonadal steroids and especially female sex hormones modulate the risk of developing epileptic seizures. In most circumstances, estrogens increase excitability, while progesterone bears substantial anticonvulsive properties. We questioned whether exogenous gonadal steroids used as hormonal contraception are associated with risk of seizures.

High expression of cystine-glutamate antiporter xCT (SLC7A11) is an independent biomarker for epileptic seizures at diagnosis in glioma.

Epileptic seizures are an important cause of morbidity in glioma patients. Substantial lines of evidence support the concept of the excitatory neurotransmitter glutamate being a crucial mediator of glioma-associated seizures. In gliomas, non-vesicular secretion of glutamate via the cystine-glutamate exchanger (SLC7A11, xCT) constitutes the main mechanism contributing to high extracellular glutamate concentrations.

Glioblastoma cancer stem cell lines express functional acid sensing ion channels ASIC1a and ASIC3.

Acidic microenvironment is commonly observed in tumour tissues, including glioblastoma (GBM), the most aggressive and lethal brain tumour in adults. Acid sensing ion channels (ASICs) are neuronal voltage-insensitive sodium channels, which are sensors of extracellular protons. Here we studied and functionally characterized ASICs in two primary glioblastoma stem cell lines as cell culture models.

Resistance to valproic acid as predictor of treatment resistance in genetic generalized epilepsies.

This study aimed at defining clinical predictors of drug resistance in adults with genetic generalized epilepsy (GGE) who were treated with a broad spectrum of antiepileptic drugs. Of a cohort of 137 unselected adult GGE patients with long-term follow up, clinical and demographic data, putative prognostic factors (e.g.

Predictive value of the Status Epilepticus Severity Score (STESS) and its components for long-term survival.

Background: The "Status Epilepticus Severity Score" (STESS) is the most important clinical score to predict in-hospital mortality of patients with status epilepticus (SE), but its prognostic relevance for long-term survival is unknown. This study therefore examined if STESS and its components retain their prognostic relevance beyond acute treatment.

Methods: One hundred twenty-five non-anoxic patients with SE were retrospectively identified in two hospitals between 2008 and 2014 (39.

The Neuroradiological Spectra of Adult and Pediatric Medulloblastoma Differ : Results from a Literature-based Meta-analysis.

Purpose: Current knowledge on the spectrum of the neuroradiological appearance of adult medulloblastoma is sparse. Due to the rarity of the disease, adult patients were generally diagnosed and treated similar to children; however, pediatric and adult medulloblastomas display substantial molecular differences that may influence the neuroradiological phenotype. This study therefore aimed at assessment of the neuroradiological spectrum of adult medulloblastoma in comparison to pediatric tumors.

Chemotherapy increases long-term survival in patients with adult medulloblastoma--a literature-based meta-analysis.

Background: Adult medulloblastoma is a potentially curable malignant entity with an incidence of 0.5-1 per million. Valid data on prognosis, treatment, and demographics are lacking, as most current knowledge stems from retrospective studies.

Chemoresistance and chemotherapy targeting stem-like cells in malignant glioma.

Glioblastoma remains a tumor with a dismal prognosis because of failure of current treatment. Glioblastoma cells with stem cell (GSC) properties survive chemotherapy and give rise to tumor recurrences that invariably result in the death of the patients. Here we summarize the current knowledge on chemoresistance of malignant glioma with a strong focus on GSC.

High levels of c-Met is associated with poor prognosis in glioblastoma.

The tyrosine kinase receptor c-Met has been suggested to be involved in crucial parts of glioma biology like tumor stemness, growth and invasion. The aim of this study was to investigate the prognostic value of c-Met in a population-based glioma patient cohort. Tissue samples from 238 patients with WHO grade I, II, III and IV tumors were analyzed using immunohistochemical staining and advanced image analysis.