Seizure and epilepsy publication in nonneurology journals.

PURPOSE: The prevalence and characteristics of seizure and epilepsy research published in nonneurology journals are unknown. Characterizing this published research allows for insight into the relevance of seizures and epilepsy in other specialties and may increase opportunity for cross-specialty collaboration. METHODS: In this observational study, we reviewed the top five highly cited clinical journals within eleven specialties in the InCites Journal Citation Reports (JCR) database (2016). For each specialty, we collected 2013-2017 PubMed data on publications with MeSH Major Topic of "seizures," "epilepsy," or "status epilepticus." Medical subject headings (MeSH) in PubMed are standardized terms assigned by subject analysts. MeSH Major Topic identifies articles in which a specified topic is the major focus of the article. We also retrieved author country and medical specialty affiliations. We analyzed whether author specialty affiliation was 1) concordant with journal medical specialty, 2) neurology-related, or 3) other. RESULTS: Articles on "seizures," "epilepsy," or "status epilepticus" had the following prevalence in specialty clinical journals: cardiac and cardiovascular systems (0.01%); clinical neurology (5.34%); critical care medicine (0.20%); emergency medicine (0.47%); general and internal medicine (0.44%); neuroimaging (2.05%); neurosurgery (2.23%); obstetrics and gynecology (0.16%); oncology (0.01%); pediatrics (0.69%); and psychiatry (0.23%). Within general and internal medicine, neuroimaging, and pediatrics, seizure-related articles are more likely to be first-authored by someone with a neurology-related affiliation. Within critical care medicine, emergency medicine, neurosurgery, and obstetrics and gynecology, seizure-related articles were more likely to be first-authored by someone whose affiliation is within the field. CONCLUSIONS: Our study characterizes seizure and epilepsy research published in nonneurology journals. We found that there is a paucity of such research published in nonneurology journals, whether authored by neurologists or other specialists. This is not ideal since nonneurologists are often first-line providers for recognizing, diagnosing, or managing seizures prior to assessment by a neurologist. Cross-specialty collaboration should be strongly encouraged in clinical research.

Predictors of seizures in patients with posterior reversible encephalopathy syndrome.

PURPOSE: Although seizures are common in patients with posterior reversible encephalopathy syndrome (PRES), epilepsy is rare. Our objective was to identify predictors and impact of seizures in patients with PRES. METHODS: A retrospective review of the clinical and radiological parameters of all patients diagnosed with PRES from 2007 to 2014 was performed. Patients were divided into two groups based on the occurrence of PRES-related seizures at presentation or during their hospital course. Univariate and multivariate analyses were performed to determine factors associated with the occurrence of PRES-related seizures. RESULTS: Of 100 patients, 70% experienced at least one seizure from PRES. On univariate analysis, the factors associated with seizures were the following: high Charlson comorbidity index (4.16±2.89 vs. 2.87±2.20, p=0.03), systemic malignancy (41.4% vs. 16.7%, p=0.02), occipital lobe involvement (97.1% vs. 83.3%, p=0.02), more lobes involved (4.6±1.48 vs. 3.9±1.32, p=0.03) but less likely in patients with visual disturbances (15.7% vs. 46.7%, p=0.005), and facial droop (12.9% vs. 16.7%, p=0.002). On multivariate analysis, only occipital lobe involvement was significantly (odds ratio: 9.63, 95% CI: 1.45-64.10, p=0.02) associated with the occurrence of PRES-related seizures. Despite the occurrence of seizures, they were less likely to require a nursing home placement upon hospital discharge (odds ratio: 0.17, 95% CI: 0.03-0.91, p=0.04). CONCLUSION: We conclude that seizures are common in patients with occipital lobe involvement from PRES.

Gain-of-function mutation in Gnao1: a murine model of epileptiform encephalopathy (EIEE17)?

G protein-coupled receptors strongly modulate neuronal excitability but there has been little evidence for G protein mechanisms in genetic epilepsies. Recently, four patients with epileptic encephalopathy (EIEE17) were found to have mutations in GNAO1, the most abundant G protein in brain, but the mechanism of this effect is not known. The GNAO1 gene product, Gαo, negatively regulates neurotransmitter release. Here, we report a dominant murine model of Gnao1-related seizures and sudden death. We introduced a genomic gain-of-function knock-in mutation (Gnao1 (+/G184S)) that prevents Go turnoff by Regulators of G protein signaling proteins. This results in rare seizures, strain-dependent death between 15 and 40 weeks of age, and a markedly increased frequency of interictal epileptiform discharges. Mutants on a C57BL/6J background also have faster sensitization to pentylenetetrazol (PTZ) kindling. Both premature lethality and PTZ kindling effects are suppressed in the 129SvJ mouse strain. We have mapped a 129S-derived modifier locus on Chromosome 17 (within the region 41-70 MB) as a Modifer of G protein Seizures (Mogs1). Our mouse model suggests a novel gain-of-function mechanism for the newly defined subset of epileptic encephalopathy (EIEE17). Furthermore, it reveals a new epilepsy susceptibility modifier Mogs1 with implications for the complex genetics of human epilepsy as well as sudden death in epilepsy.

Levetiracetam-induced thrombocytopenia among inpatients: a retrospective study.

Lately, few case reports have brought forth limited cases of levetiracetam (LEV)-induced thrombocytopenia. To estimate the burden of LEV-induced thrombocytopenia, we reviewed medical records of 758 patients aged 18 years or older who received LEV during their stay at the University Hospital from June 2005 to December 2008. In patients identified with thrombocytopenia, records were reviewed to establish a cause of thrombocytopenia and possible causal role of LEV. Of 758 patients, 29 patients were identified with thrombocytopenia while on LEV therapy. For 23 patients, an alternative cause for thrombocytopenia was established; 4 patients had preexisting thrombocytopenia without any appreciable change in platelet count after addition of LEV. One patient had limited data for identifying the cause of thrombocytopenia. A single patient had clear temporal co-relation and association of thrombocytopenia with LEV therapy. LEV-induced thrombocytopenia is a rare but reversible complication of LEV therapy. The mechanism remains unknown.

Catatonia in encephalitis and nonconvulsive seizures: a case report and review of the literature.

A 20-year-old woman was admitted for psychosis. On further investigation, she was found to be have viral encephalitis and generalized nonconvulsive seizures. After the seizures were controlled, she remained in a prolonged catatonic state. Repeated intravenous benzodiazepine administration, improved her cognition dramatically. This case emphasizes that catatonia may occur after encephalitis and nonconvulsive seizures.

Positive clinical signs in neurological diseases - An observational study.

Many patients with organic neurological disease have symptoms and signs that are unexplained by their disease condition. We attempted to explore the prevalence of positive clinical signs in patients with various organic neurological diseases. We performed a prospective uncontrolled observational study on the presence of 7 positive signs in adults with various organic neurological diseases that were admitted to our tertiary care hospital. This observation was performed during their neurological examination in those who provided consent, could comprehend and lacked terminal illness or profound weakness that limited their ability to perform these tasks. We dichotomized them into two groups based on the presence of these signs. Out of 190 patients that were evaluated between 2014 and 2015, 37 patients had at least one positive sign. On univariate analysis: young age, female gender, prior anxiety, history of childhood abuse, identification of sensory deficits on examination and lack of imaging correlation with clinical localization were identified as risk factors for these positive signs. On multivariate analysis, anxiety (OR 2.88, 95% CI 1.11-7.49, p = 0.03) and presence of sensory deficits on examination (OR 5.81, 95% CI 2.36-14.32, p ≤ 0.001) were associated with these positive signs. Positive signs are common in patients with organic neurological diseases that have anxiety or sensory deficits and may imply a component of functional overlay. Large studies are required to understand its pathophysiology and impact on future outcomes.

Curcumin has anticonvulsant activity on increasing current electroshock seizures in mice.

Epilepsy is one of the most common serious disorders of the brain. Several experimental studies have reported neuroprotective and antioxidant activity of certain natural products like curcumin, an active ingredient of turmeric. The present study was designed to explore the effect of acute administration of curcumin at doses 50, 100 and 200 mg/kg, orally (p.o.) and its chronic (x 21 days) administration in 100 mg/kg, p.o. on increasing current electroshock (ICES) test, elevated plus maze and actophotometer in mice. Curcumin in a dose of 100 mg/kg significantly increased the seizure threshold in ICES test on both acute and chronic administration. The same dose of 100 mg/kg on acute administration showed anxiogenic effect on elevated plus maze and actophotometer test. However, this anxiogenic effect of curcumin disappeared on chronic administration. These results suggest that curcumin appears to possess anticonvulsant activity in mice.

Reversal of lindane-induced impairment of step-down passive avoidance and oxidative stress by neurosteroids in rats.

Neurosteroids (NS) are recognized as important modulators of functioning of the nervous system. Lindane, an organochlorine pesticide has been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was designed to explore the modulation of effects of lindane over cognitive function by progesterone (PROG), pregnenolone sulfate (PREG-S) and 4'-chlorodiazepam (4CD). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on a plus maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and non-protein thiol (NP-SH) levels. A significant reduction in SDL was found for the lindane treated group at weeks 6 and 7 as compared to control (p<0.001). One-week treatment by PREG-S or 4CD antagonized the effect of lindane on SDL. PROG failed to modulate the effect of lindane on SDL. Lindane caused a significant prolongation of TL as compared to control (p<0.001) from second week onwards. One-week administration of PROG, PREG-S or 4CD was unable to reverse this prolongation of TL. Lindane produced a statistically significant increase in the brain MDA levels (p<0.001) and significant decrease in the brain NP-SH levels (p<0.001). Treatment with PREG-S and 4CD attenuated the effect of lindane on MDA (p<0.001) and NP-SH levels. PROG failed to influence oxidative stress induced by lindane. Results of the present study thus show that some NS have potential in reversing cognitive dysfunction and oxidative stress induced by toxicants like lindane in the brain.

Universal automated high frequency oscillation detector for real-time, long term EEG.

OBJECTIVE: Interictal high frequency oscillations (HFOs) in intracranial EEG are a potential biomarker of epilepsy, but current automated HFO detectors require human review to remove artifacts. Our objective is to automatically redact false HFO detections, facilitating clinical use of interictal HFOs. METHODS: Intracranial EEG data from 23 patients were processed with automated detectors of HFOs and artifacts. HFOs not concurrent with artifacts were labeled quality HFOs (qHFOs). Methods were validated by human review on a subset of 2000 events. The correlation of qHFO rates with the seizure onset zone (SOZ) was assessed via (1) a retrospective asymmetry measure and (2) a novel quasi-prospective algorithm to identify SOZ. RESULTS: Human review estimated that less than 12% of qHFOs are artifacts, whereas 78.5% of redacted HFOs are artifacts. The qHFO rate was more correlated with SOZ (p=0.020, Wilcoxon signed rank test) and resected volume (p=0.0037) than baseline detections. Using qHFOs, our algorithm was able to determine SOZ in 60% of the ILAE Class I patients, with all algorithmically-determined SOZs fully within the resected volumes. CONCLUSIONS: The algorithm reduced false-positive HFO detections, improving the precision of the HFO-biomarker. SIGNIFICANCE: These methods provide a feasible strategy for HFO detection in real-time, continuous EEG with minimal human monitoring of data quality.

Nocebo effect in Dermatology.

Nocebo effect, originally denoting the negative counterpart of the placebo phenomenon, is now better defined as the occurrence of adverse effects to a therapeutic intervention because the patient expects them to develop. More commonly encountered in patients with a past negative experience, this effect stems from highly active processes in the central nervous system, mediated by specific neurotransmitters and modulated by psychological mechanisms such as expectation and conditioning. The magnitude of nocebo effect in clinical medicine is being increasingly appreciated and its relevance encompasses clinical trials as well as clinical practice. Although there is hardly any reference to the term nocebo in dermatology articles, the phenomenon is encountered routinely by dermatologists. Dermatology patients are more susceptible to nocebo responses owing to the psychological concern from visibility of skin lesions and the chronicity, unpredictable course, lack of 'permanent cure' and frequent relapses of skin disorders. While finasteride remains the prototypical drug that displays a prominent nocebo effect in dermatologic therapeutics, other drugs such as isotretinoin are also likely inducers. This peculiar phenomenon has recently been appreciated in the modulation of itch perception and in controlled drug provocation tests in patients with a history of adverse drug reactions. Considering the conflict between patients' right to information about treatment related adverse effects and the likelihood of nocebo effect stemming from information disclosure, the prospect of ethically minimizing nocebo effect remains daunting. In this article, we review the concept of nocebo effect, its postulated mechanism, relevance in clinical dermatology and techniques to prevent it from becoming a barrier to effective patient management.

Intraoperative monitoring for intracranial aneurysms: the Michigan experience.

Intraoperative neurophysiological monitoring is routinely used during the repair (endovascular or microsurgical) of intracranial aneurysms at major centers. There is a continued need of data sets from institutions with dedicated intraoperative neurophysiological monitoring services to further define the predictive factors of postoperative neurological deficits. We retrospectively reviewed and analyzed our database of all patients who underwent repair of intracranial aneurysms (endovascular or microsurgical). A total of 406 patients underwent 470 procedures. The changes were noted during monitoring in 3.83% of the cases. Most of the changes were first detected in somatosensory evoked potential (88.89%) followed by brainstem auditory evoked potential (16.67%). Changes were completely reversible in 44.44%, only partly reversible in 22.22%, and irreversible in 33.33% of cases. Intraoperative neurophysiological monitoring changes demonstrated high sensitivity, specificity, and negative predictive value for postoperative neurological deficits. The association between intraoperative neurophysiological monitoring changes and Glasgow outcome scale was significant for reversible changes compared against irreversible and partly reversible changes. Presence of any intraoperative neurophysiological monitoring modality change during repair of intracranial aneurysm may suggest a higher risk for postoperative neurological deficits. Reversibility of the changes is a favorable marker, whereas irreversible changes are predictive of postoperative neurological deficits with deterioration of Glasgow outcome scale on a longer follow-up.

Opinion survey of health care providers towards psychogenic non epileptic seizures.

OBJECTIVES: Psychogenic non epileptic seizures (PNES) are challenging conditions to diagnose and manage. Previous workers have investigated the opinion of health care providers towards PNES; still several lacunae remain to be stressed. Amongst health care professionals, opinion of nurses has not been adequately explored. We attempted to identify areas which need more emphasis to provide optimal care to the patients. PATIENTS AND METHODS: We approached 417 health care providers (HCP; primary care, neurology and in-patient nurses) with a questionnaire regarding their opinion of PNES. RESULTS: Total 115 respondents responded to our survey. We found one-thirds of respondent favoured "non-epileptic seizure" as the preferred diagnostic term. Although majority (61%) of responders felt that PNES were involuntary, 48% of nurses felt that PNES are 'fake' and patients have voluntary control over them. Neurologists and nurses expressed high level of confidence in managing patients of PNES. About 1/3rd (35%) of responders did not feel video EEG (vEEG) to be always required for the diagnosis of PNES. Only a minority (15%) of healthcare providers favor unrestricted driving by patients of PNES in setting of ongoing seizures. CONCLUSION: Our findings highlight areas where more emphasis needs to be placed regarding PNES amongst HCPs. More emphasis needs to be placed on the involuntary nature of these episodes within the HCP community. It might be necessary to more strongly address the education of nurses and residents for this condition.

Psychogenic non-epileptic seizures: a challenging entity.

Psychogenic non-epileptic seizures (PNES) are commonly encountered in neurologic practice. They are often misdiagnosed as epileptic seizures and treated as such for several years before a correct diagnosis is established. Such a misdiagnosis has the potential to expose patients to undue risk through several anti-epileptic drugs (AEDs). Patients are also affected in other ways, such as by financial consequences and the limitation of certain daily activities. In this review, we present the contemporary opinion of PNES with attention to clinically relevant salient features and management strategies.

Venous sinus thrombosis and consumptive coagulopathy: a role for heparin?

Cerebral venous sinus thrombosis is a relatively rare but serious condition, more commonly affecting children and pregnant women. It can be precipitated by dehydration. Despite the frequent coexistence of hemorrhage in venous infarcts of patients, clinical trials in adults recommended the use of anticoagulation. No randomized, clinical trials exist in the pediatric age group. Rarely, consumptive coagulopathy is reported to coexist with cerebral venous sinus thrombosis. We report on a child with venous sinus thrombosis and consumptive coagulopathy developing after routine tonsillectomy and its successful management with anticoagulation.

Electroencephalographic abnormalities in baclofen-induced encephalopathy.

We report a patient in whom the characteristic electroencephalographic features of baclofen intoxication are highlighted and emphasize the role of electrographic abnormalities in the diagnosis of this condition.

Recurrent epileptic Wernicke aphasia.

We report a patient with recurrent epileptic Wernicke aphasia who prior to this presentation, had been misdiagnosed as transient ischemic attacks for several years. This case report emphasizes the consideration of epileptic nature of aphasia when a clear alternate etiology is unavailable, even when EEG fails to show a clear ictal pattern. We also present a brief discussion of previously reported ictal aphasias.