Diagnostic biomarkers of epilepsy are objectively measurable variables associated with the development of epilepsy or the propensity to generate seizures. Identification of biomarkers could be ...helpful for differential diagnosis and for tailored therapeutic approaches.
This review focuses on diagnostic biomarkers of epilepsy, including genetic, serological, neuroimaging and electrophysiological variables.
References were mainly identified through PubMed search until December 2017 and backtracking of references in pertinent studies.
Several promising diagnostic biomarkers of epilepsy exist, with causative value or predicting liability to develop seizures after acquired brain injuries. Short non-coding RNAs are deregulated in serum and cerebral tissue of epilepsy subjects: these molecules are promising diagnostic biomarkers, being easy to assess and reproducible. Advanced imaging techniques may allow identification of subtle epileptogenic lesions, often with prognostic value. Novel electrophysiological biomarkers of epilepsy include perturbed cortical connectivity and excitability induced by transcranial magnetic stimulation, as well as high-frequency oscillations detected by intracranial and scalp electroencephalographic recordings. Finally, serological biomarkers may support the differential diagnosis between epileptic seizures and non-epileptic events.
Ongoing research on diagnostic biomarkers of epilepsy is promising and future preclinical and clinical studies are warranted.
Background
Epilepsy and hypertension are common chronic conditions, both showing high prevalence in older age groups. This review outlines current experimental and clinical evidence on both direct ...and indirect role of hypertension in epileptogenesis and discusses the principles of drug treatment in patients with hypertension and epilepsy.
Methods
We selected English-written articles on epilepsy, hypertension, stroke, and cerebrovascular disease until December, 2018.
Results
Renin-angiotensin system might play a central role in the direct interaction between hypertension and epilepsy, but other mechanisms may be contemplated. Large-artery stroke, small vessel disease and posterior reversible leukoencephalopathy syndrome are hypertension-related brain lesions able to determine epilepsy by indirect mechanisms. The role of hypertension as an independent risk factor for post-stroke epilepsy has not been demonstrated. The role of hypertension-related small vessel disease in adult-onset epilepsy has been demonstrated. Posterior reversible encephalopathy syndrome is an acute condition, often caused by a hypertensive crisis, associated with the occurrence of acute symptomatic seizures. Chronic antiepileptic treatment should consider the risk of drug-drug interactions with antihypertensives.
Conclusions
Current evidence from preclinical and clinical studies supports the vision that hypertension may be a cause of seizures and epilepsy through direct or indirect mechanisms. In both post-stroke epilepsy and small vessel disease-associated epilepsy, chronic antiepileptic treatment is recommended. In posterior reversible encephalopathy syndrome blood pressure must be rapidly lowered and prompt antiepileptic treatment should be initiated.
•BRV proved to be useful and safe for the treatment of status epilepticus.•Time to seizures resolution appears shorter when it is administered in the early phases of status epilepticus.•The use of ...the BRV within 6 h from SE onset was independently associated to an early seizures’ resolution.•No severe treatment emergent adverse events were observed.
to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE).
a retrospective multicentric study involving 24 Italian neurology units was performed from March 2018 to June 2020. A shared case report form was used across participating centres to limit biases of retrospective data collection. Diagnosis and classification of SE followed the 2015 ILAE proposal. We considered a trial with BRV a success when it was the last administered drug prior the clinical and/or EEG resolution of seizures, and the SE did not recur during hospital observation. In addition, we considered cases with early response, defined as SE resolved within 6 h after BRV administration.
56 patients were included (mean age 62 years; 57 % male). A previous diagnosis of epilepsy was present in 21 (38 %). Regarding SE etiology classification 46 % were acute symptomatic, 18 % remote and 16 % progressive symptomatic. SE episodes with prominent motor features were the majority (80 %). BRV was administered as first drug after benzodiazepine failure in 21 % episodes, while it was used as the second or the third (or more) drug in the 38 % and 38 % of episodes respectively. The median loading dose was 100 mg (range 50−300 mg). BRV was effective in 32 cases (57 %). An early response was documented in 22 patients (39 % of the whole sample). The use of the BRV within 6 h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39–202; p = 0.002). No severe treatment emergent adverse events were observed.
BRV proved to be useful and safe for the treatment of SE. Time to seizures resolution appears shorter when it is administered in the early phases of SE.
Déjà vu (DV) is a fascinating and mysterious human experience that has attracted interest from psychologists and neuroscientists for over a century. In recent years, several studies have been ...conducted to unravel the psychological and neurological correlates of this phenomenon. However, the neural mechanisms underlying the DV experience in benign manifestations are still poorly understood.
Thirty-three healthy volunteers completed an extensive neuropsychiatric and neuropsychological battery including personality evaluation. The presence of DV was assessed with the Inventory for Deja vu Experiences Assessment. Participants underwent episodic memory learning test, and 2 days later during event-related functional magnetic resonance imaging (fMRI), they are asked to rate old and new pictures as a novel, moderately/very familiar, or recollected.
We identified 18 subjects with DV (DV+) and 15 without DV (DV−) matched for demographical, neuropsychological, and personality characteristics. At a behavioral level, no significant difference was detected in the episodic memory tasks between DV+ and DV−. Functional magnetic resonance imaging analysis revealed that DV+, independently from task conditions, were characterized by increased activity of the bilateral insula coupled with reduced activation in the right parahippocampal, both hippocampi, superior/middle temporal gyri, thalami, caudate nuclei, and superior frontal gyri with respect to DV−. Our study demonstrates that individuals who experienced DV are not characterized by different performance underlying familiarity/recollection memory processes. However, fMRI results provide evidence that the physiological DV experience is associated with the employment of different neural responses of brain regions involved in memory and emotional processes.
•DV is associated with functional changes in the memory and emotional regions.•Subjects with DV+ showed less activation in the parahippocampal and middle temporal gyrus.•Subjects with DV+ showed more activation in the left insula.•DV may be considered as an interindividual tendency to elaborate external information.
•This cohort study analyzed predictors of occurrence and recurrence of SE in a large sample.•SE occurrence was linked to advanced age, female sex, and definite etiology.•SE recurrence was about 20%.
...Status epilepticus (SE) is associated with high morbidity and mortality. This multicenter retrospective cohort study aims to identify the factors associated with the occurrence of SE and the predictors of its recurrence in patients with adult–onset seizures.
We retrospectively analyzed data of 1115 patients with seizure onset>18 years, observed from 1983 to 2020 in 7 Italian Centers (median follow–up 2.1 years). Data were collected from the databases of the Centers. Patients with SE were consecutively recruited, and patients without SE history were randomly selected in a 2:1 ratio. To assess determinants of SE, different clinical–demographic variables were evaluated and included in univariate and multivariate logistic regression model.
Three hundred forty–seven patients had a SE history, whereas the remaining 768 patients had either isolated seizures or epilepsy without SE history. The occurrence of SE was independently associated with increasing age at onset of disease (OR 1.02, 95% CI 1.01––1.03, p<0.001), female sex (OR 1.39, 95% CI 1.05––1.83, p=0.02) and known etiology (OR 3.58, 95% CI 2.61––4.93, p<0.001). SE recurred in 21% of patients with adult–onset SE and recurrence was associated with increasing number of anti–seizure medications taken at last follow–up (OR 1.88, 95% CI 1.31––2.71, p<0.001).
In patients with adult–onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events.
The Inventory Déjà Vu Experiences Assessment (IDEA) is the only screening instrument proposed to evaluate the Déjà vu (DV) experience. Here, we intended to validate the Italian version of IDEA ...(I-IDEA) and at the same time to investigate the incidence and subjective qualities of the DV phenomenon in healthy Italian adult individuals on basis of an Italian multicentre observational study. In this study, we report normative data on the I-IDEA, collected on a sample of 542 Italian healthy subjects aging between 18-70 years (average age: 40) with a formal educational from 1-19 years. From September 2013 to March 2016, we recruited 542 healthy volunteers from 10 outpatient neurological clinics in Italy. All participants (i.e., family members of neurological patients enrolled, medical students, physicians) had no neurological or psychiatric illness and gave their informed consent to participate in the study. All subjects enrolled self-administered the questionnaire and they were able to complete I-IDEA test without any support. In total, 396 (73%) of the 542 healthy controls experienced the DV phenomenon. The frequency of DV was inversely related to age as well as to derealisation, jamais vu, precognitive dreams, depersonalization, paranormal activity, remembering dreams, travel frequency, and daydreams (all
< 0.012). The Italian version of IDEA maintains good properties, thus confirming that this instrument is reliable for detecting and characterising the DV phenomenon.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The pathogenic association between Chlamydophila psittaci (Cp) and ocular adnexal marginal zone lymphoma (OAMZL) and the efficacy of doxycycline monotherapy have been investigated in retrospective ...series with variations in stage, management, and follow-up duration. To our knowledge, this is the first international phase II trial aimed at clarifying Cp prevalence and activity of first-line doxycycline in a homogeneous series of consecutive patients with newly diagnosed stage I OAMZL.
Forty-seven patients were registered. Tumor tissue, conjunctival swabs, and peripheral blood from 44 patients were assessed for seven Chlamydiaceae infections by three polymerase chain reaction protocols. Thirty-four patients with measurable or parametrable disease were treated with doxycycline and assessed for chlamydial eradication and lymphoma response (primary end point).
Cp DNA was detected in biopsies of 39 patients (89%); no other Chlamydiaceae were detected. Twenty-nine patients had Cp DNA in baseline swabs and/or blood samples and were evaluable for chlamydial eradication, which was achieved in 14 patients (48%). Lymphoma regression was complete in six patients and partial in 16 (overall response rate, 65%; 95% CI, 49% to 81%); 11 had stable disease, and one had progressive disease. At a median follow-up of 37 months (range, 15 to 62 months), 20 patients remained relapse free (5-year progression-free survival PFS ± standard deviation, 55% ± 9%). Cp eradication was associated with improved response rate (86% v 47%; P = .02) and 5-year PFS (68% v 47%; P = .11).
Upfront doxycycline is a rational and active treatment for patients with stage I Cp-positive OAMZL. Lymphoma regression is consequent to Cp eradication, which can easily be monitored on conjunctival and blood samples. Prospective trials aimed at identifying more effective administration schedules for doxycycline are warranted.
Abstract In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d -chiro-inositol (DCI), because of their involvement, as second ...messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2 g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI).
Abstract Objective Essential Tremor with resting tremor (rET) is a debated and poorly understood clinical phenotype. Converging evidences show that neurodegeneration of the cerebellum underlies the ...pathophysiology of ET, but it is not known if cerebellar changes also occurs in patients with rET. The aim of our study was to evaluate cerebellar microstructure in patients with ET with- (rET) and without resting tremor (ETwr) in comparison to healthy controls by MR Diffusion Tensor Imaging (DTI). Methods We studied 67 patients with ET (rET: 29 and ETwr: 38) and 39 age-matched healthy controls (HC). DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) of white and grey matter (WM, GM) in the entire cerebellum and in right and left cerebellar hemispheres. Results MD was significantly higher in the cerebellar GM of ET total group (10.39 ± 0.87) in comparison with HC (9.90 ± 0.71) (p = 0.0027). Interestingly, MD was significantly different when ETwr (10.48 ± 0.77) were compared with HC (p = 0.0017), whereas a trend toward significance were found between rET (10.29 ± 0.99) and HC (p = 0.067). No differences among groups were found in MD of cerebellar WM and in FA values neither in the WM nor in the GM. Conclusion Our results demonstrate the presence of microstructural changes in the cerebellum of patients with ET. It is noteworthy that rET showed intermediate values compared to HC and ETwr, suggesting that rET shares part of the pathophysiological mechanisms of ETwr, but cerebellar involvement seems do not fully account for rET. In addition to the cerebellar loops, other networks may play a role in rET pathophysiology.