Inflammatory and neurotrophic factor plasma levels are related to epilepsy independently of etiology.

OBJECTIVE: Inflammation plays an essential role in epilepsy. Studies indicate that cytokines and neurotrophic factors can act in neuroexcitability and epileptogenesis. We aimed to investigate the association between plasma inflammatory and neurotrophic markers, seizure frequency, and chronic epilepsy subtypes. METHODS: We studied 446 patients with epilepsy and 166 healthy controls. We classified patients according to etiology and seizure frequency. We measured plasma levels of interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-γ (IFNγ), tumor necrosis factor α (TNFα), soluble TNF receptor 1 (sTNFr1), sTNFr2, brain-derived neurotrophic factor (BDNF), neurotrophic factor 3 (NT3), NT4/5, ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) by enzyme-linked immunosorbent assay or cytometric bead array. RESULTS: The plasma levels of BDNF, NT3, NGF, and sTNFr2 were higher, whereas IL-2, IL-4, IL-6, IL-10, IL-17, IFNγ, TNFα, CNTF, and sTNFr1 were lower in patients than controls. IL1, GDNF, and NT4/5 were similar between groups. These markers did not correlate with age, sex, and epilepsy duration. The molecule sTNFr2 was the best marker to discriminate patients from controls (area under the curve = .857), also differing between patients with frequent and infrequent seizures. SIGNIFICANCE: This large cohort confirmed that patients with epilepsy have abnormal levels of plasma inflammatory and neurotrophic markers independent of the underlying etiology. Plasma level of sTNFr2 was related to seizure frequency and discriminated people with or without epilepsy with good accuracy, making it a potential biomarker for epilepsy and seizure burden.

Clinical variables that help in predicting the presence of autoantibodies in patients with acute encephalitis.

OBJECTIVE: To identify clinical variables that could predict the presence of autoantibodies in patients with acute encephalitis. METHODS: An observational, retrospective study from May 2011 to May 2017. Clinical, EEG, brain MRI data, and antibodies against human neuronal antigens (NMDAR, GABAR, AMPAR, LGI1, CASPR2, and GAD) from 158 patients with criteria for possible autoimmune encephalitis were analyzed to create a predictive model for this disease. RESULTS: We analyzed 158 samples, of which 18 cases were positive for anti-NMDAR, 2 for anti-LGI1, and 2 for anti-GAD. Seven of the 18 positive NMDAR patients were children, and 12 were female. Behavioral disorder, epileptic seizures, movement disorder, and altered level of consciousness were the frequent symptoms with >75 % sensitivity in positive anti-NMDAR patients. Other symptoms, such as language disorder, psychosis, hypoventilation, altered wake and sleep cycle, and cognitive impairment, had a sensitivity >55 %. Abnormal EEG findings had a high sensitivity (99.4 %). Brain MRI suggestive of encephalitis was observed in 7 of the positive cases for NMDAR. Abnormal CSF findings were reported in 12 patients positive for this receptor (sensitivity 70.6 %). With 7 of these symptoms, we obtained a sensitivity of 70 % and specificity of 81 % for the presence of anti-NMDAR antibodies (ROC Area 82 %). However, to predict that a patient with subacute encephalitis may have an autoimmune cause, the patient should include clinical manifestations such as movement disorder, behavioral disorder, hypoventilation, dysautonomia, and alteration of the wake and sleep cycle. Children were significantly more likely than adults with autoimmune encephalitis to experience chorea and status epilepticus (p < 0.05). CONCLUSIONS: Anti-NMDAR encephalitis was more frequent in females and children. The repertoire of autoimmune encephalitis in children is different from adults. The presence of subacute behavioral changes, epileptic seizures, movement disorders, altered consciousness, hypoventilation, dysautonomia, and altered wake and sleep cycle predicted autoimmune encephalitis in our series.

How do people with drug-resistant mesial temporal lobe epilepsy sleep? A clinical and video-EEG with EOG and submental EMG for sleep staging study.

This study aimed to assess subjective and objective sleep parameters in a homogeneous group of drug-resistant mesial temporal lobe epilepsy (MTLE) patients through internationally validated clinical questionnaires, video-electroencephalographic (VEEG) and polysomnographic (PSG) studies. Fifty-six patients with definite diagnosis of MTLE who were candidates for epilepsy surgery underwent a detailed clinical history, the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Stanford Sleepiness Scale (SSS), neurological examination, 1.5 T brain magnetic resonance imaging, VEEG and PSG. Sixteen percent of patients reported significant daytime sleepiness as measured by ESS and 27% reported low levels of sleep quality as measured by PSQI. Patients with medically resistant epilepsy by MTLE showed increased wakefulness after sleep onset (WASO) with mean ± standard deviation of 17.4 ± 15.6, longer non-rapid eye movement (NREM) 1 (7.5 ± 4.6%) and NREM3 sleep (26.6 ± 11.8%), abnormal rapid eye movement (REM) latency in 30/56 patients, shorter REM sleep (16.7 ± 6.6%), and abnormal alpha delta patterns were observed in 41/56 patients. The analysis of interictal epileptic discharges (IEDs) evidenced highest spiking rate during NREM3 sleep and higher concordance with imaging data when IEDs were recorded in sleep, mainly during REM sleep. We concluded that patients with MTLE showed disrupted sleep architecture that may result in daytime dysfunction and sleep complaints. Furthermore, NREM sleep activated focal IEDs and them - when recorded during sleep - had higher localizing value.

Excessive sleepiness and sleep patterns in patients with epilepsy: a case-control study.

The aim of this study was to assess excessive daytime sleepiness (EDS), sleep quality, and sleep disorders in a cohort of patients with epilepsy in the city of Florianopolis in southern Brazil. One hundred and forty patients diagnosed with epilepsy were assessed by questionnaires that included demographic and clinical variables, the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Stanford Sleepiness Scale (SSS), and the Fletcher & Luckett Adapted Questionnaire (FLAQ). These data were then compared to data from a control group (n=85). Compared to controls, patients with epilepsy (PWE) had significantly higher scores on the ESS (p=0.003), higher scores on the "daytime dysfunction" domain of the PSQI (p=0.002), and more symptoms that suggested obstructive sleep apnea in the FLAQ (p<0.001). By performing multiple linear regression models, we demonstrated that age, male gender, the presence of secondarily generalized seizures, and phenobarbital use were slightly to moderately correlated with PSQI (r=0.38) and FLAQ (r=0.51) but not with SSS scores. We concluded that PWE had more EDS, daytime dysfunction, and sleep disorders compared to a control group.

Distrofia miotônica tipo 1: um relato de caso / Myotonic dystrophy type 1: a case report

A distrofia miotônica tipo I (DM1) é considerada aforma mais comum de miopatia em adultos, sendo caracterizadaclinicamente por fraqueza muscular, evidênciasclínicas de miotonia e uma história familiarpositiva. Apresenta, no entanto, uma grande variabilidadefenotípica, podendo ser encontradas manifestaçõesclínicas multissistêmicas (cardíacas, endócrinas,gastrointestinais, oftalmológicas e cognitivas) que podemdificultar seu diagnóstico. Relato de caso: pacientemasculino de 26 anos iniciou há 10 anos com quadrode fraqueza em membros superiores e inferiores. Apósanos sem melhora clínica, confirmou-se o diagnósticode DM1. Neste relato de caso ressalta-se a importânciada história clínica e exame físico do paciente para odiagnóstico de DM1.

Myotonic dystrophy type 1 (dystrophic myotonia type1 or DM1) is a muscle disorder, inherited in an autosomaldominant fashion, characterized by muscle wastingand weakness associated with myotonia and a numberof other systemic abnormalities, including cardiological,endocrine, gastroenterological, ophthalmological anddevelopmental impairment. A 26-year-old male patient,started 10 years ago with progressive superior and inferiorlimb weakness, associated with agoraphobia. Initiallyhe received the diagnosis of panic disorder and he wastreated with antidepressants. After years without clinicalimprovement, the diagnosis of DM1 was confirmed.Few diseases are as easy to recognize as DM1 once thediagnosis is considered. Conversely, misdiagnosis occurswhen the presenting complaint may be unrelated to thebasic problem, with patients presenting themselves tomany different specialists.

Multiplex assay for comprehensive genotyping of genes involved in drug metabolism, excretion, and transport.

BACKGROUND: Drug metabolism is a multistep process by which the body disposes of xenobiotic agents such as therapeutic drugs. Genetic variation in the enzymes involved in this process can lead to variability in a patient's response to medication. METHODS: We used molecular-inversion probe technology to develop a multiplex genotyping assay that can simultaneously test for 1227 genetic variants in 169 genes involved in drug metabolism, excretion, and transport. Within this larger set of variants, we performed analytical validation of a clinically defined core set of 165 variants in 27 genes to assess accuracy, imprecision, and dynamic range. RESULTS: In a test set of 91 samples, genotyping accuracy for the core set probes was 99.8% for called genotypes, with a 1.2% no-call (NC) rate. The majority of the core set probes (133 of 165) had < or = 1 genotyping failure in the test set; a subset of 12 probes was responsible for the majority of failures (mainly NC). Genotyping results were reproducible upon repeat testing with overall within- and between-run variation of 1.1% and 1.4%, respectively-again, primarily NCs in a subset of probes. The assay showed stable genotyping results over a 6-fold range of input DNA. CONCLUSIONS: This assay generates a comprehensive assessment of a patient's metabolic genotype and is a tool that can provide a more thorough understanding of patient-to-patient variability in pharmacokinetic responses to drugs.

Comprehensive assessment of metabolic enzyme and transporter genes using the Affymetrix Targeted Genotyping System.

The combined effects of multiple polymorphisms in several drug-metabolizing enzyme and transporter genes can contribute to considerable interindividual variation in drug disposition and response. Therefore, it has been of increasing interest to generate scalable, flexible and cost-effective technologies for large-scale genotyping of the drug-metabolizing enzyme and transporter genes. However, the number of drug-metabolizing enzyme and transporter gene variants exceeds the capacity of current technologies to comprehensively assess multiple polymorphisms in a single, multiplexed assay. The Targeted Genotyping System (Affymetrix, CA, USA) provides a solution to this challenge, by combining molecular inversion probe technology with universal microarrays to provide a method that is capable of analyzing thousands of variants in a single reaction, while remaining relatively insensitive to cross-reactivity between reaction components. This review will focus on the Targeted Genotyping System and how this technology was adapted to enable comprehensive analysis of drug-metabolizing enzyme and transporter gene polymorphisms.