Modulation of neuronal activity in human centromedian nucleus during an auditory attention and working memory task.

Centromedian nucleus (CM) is one of several intralaminar nuclei of the thalamus and is thought to be involved in consciousness, arousal, and attention. CM has been suggested to play a key role in the control of attention, by regulating the flow of information to different brain regions such as the ascending reticular system, basal ganglia, and cortex. While the neurophysiology of attention in visual and auditory systems has been studied in animal models, combined single unit and LFP recordings in human have not, to our knowledge, been reported. Here, we recorded neuronal activity in the CM nucleus in 11 patients prior to insertion of deep brain stimulation electrodes for the treatment of epilepsy while subjects performed an auditory attention task. Patients were requested to attend and count the infrequent (p = 0.2) odd or "deviant" tones, ignore the frequent standard tones and report the total number of deviant tones at trial completion. Spikes were discriminated, and LFPs were band pass filtered (5-45 Hz). Average peri­stimulus time histograms and spectra were constructed by aligning on tone onsets and statistically compared. The firing rate of CM neurons showed selective, multi-phasic responses to deviant tones in 81% of the tested neurons. Local field potential analysis showed selective beta and low gamma (13-45 Hz) modulations in response to deviant tones, also in a multi-phasic pattern. The current study demonstrates that CM neurons are under top-down control and participate in the selective processing during auditory attention and working memory. These results, taken together, implicate the CM in selective auditory attention and working memory and support a role of beta and low gamma oscillatory activity in cognitive processes. It also has potential implications for DBS therapy for epilepsy and non-motor symptoms of PD, such as apathy and other disorders of attention.

Psychogenic nonepileptic seizures in Latin America: A survey describing current practices.

OBJECTIVE: Psychogenic nonepileptic seizures (PNES) are one of the most common differential diagnoses of epilepsy. This study provides an overview of diagnostic and treatment services for patients with PNES across Latin America. METHODS: In 2017-2018, clinicians practicing in Latin America with responsibilities for patients with PNES were contacted to respond to a survey regarding the management of this disorder developed by the International League Against Epilepsy (ILAE) PNES Task Force. RESULTS: Three hundred and sixty responses from 17 Latin American countries were analyzed. Most respondents were neurologists (81%) under 40 years of age (61%). Fifty-seven percent of professionals stated that they personally diagnose PNES, but only 33% stated that they provide follow-up, and only 20% that they recommend treatment. Many participants (54%) characterized themselves as either unfamiliar with the diagnosis or inexperienced in arranging treatment. Most respondents reported having access to brain magnetic resonance imaging (MRI; 88%) and routine electroencephalogram (EEG; 71%), 64% have the access to video-EEG longer than 8 h, and 54% of professionals performed video-EEG to confirm PNES diagnoses. Although cognitive-behavioral therapy was recognized as the treatment of choice (by 82% of respondents), there was little access to it (60%). In contrast, a high proportion of respondents reported using antidepressant (67%), antiseizure (57%), and antipsychotic medications (54%) as treatments for PNES. SIGNIFICANCE: This study reveals several deficiencies in the diagnosis and treatment of patients with PNES in Latin America. The barriers are reinforced by lack of knowledge among the specialists and poor healthcare system support. There is inadequate access to prolonged video-EEG and psychotherapy. An inappropriate use of antiseizure medicines seems commonplace, and there are low follow-up rates by neurologists after the diagnosis. Multidisciplinary guidelines are required to improve the approach of patients with PNES.

Art and psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) are episodes of seizure-like symptoms that are not associated with epileptiform discharges on electroencephalogram (EEG). They can be remarkably difficult to distinguish from epileptic seizures: both may involve alterations in mental status and behavior, sensory or perceptual disturbances, as well as simple or complex motor patterns. Pictorial expressions of PNES have always attracted attention from the lay public and medical practitioners alike, by showing the rich variety of semiologies seen in the condition and its differences with epileptic seizures. In this article, we present two new contemporary artistic descriptions by the Canadian artist Iris Hauser about PNES. The depictions highlight key signs seen in PNES such as "eyes closed during events", "the hyperextension of the back and limbs", and the "claw-like finger posturing". We believe that the drawings can provide a valuable educational component in the initial assessment of patients suspected of having PNES as a training tool to identify and refer patients for more advanced testing.

Forced normalization: A systematic review.

OBJECTIVE: Forced normalization (FN) is an intriguing phenomenon characterized by the emergence of psychiatric disturbances following the establishment of seizure control or reduction in the epileptic activity in a patient with previous uncontrolled epilepsy. We aim to describe the clinical characteristics of the condition. METHODS: We conducted a systematic review on MEDLINE, EMBASE, Cochrane, and Scielo from January 1953 to January 2018. Clinical, electrographic, and imaging data were gathered. We considered all outcomes in children and adults. We performed no meta-analyses due to the limited available data. RESULTS: Of 2606 abstracts identified, 36 fulfilled the FN diagnostic criteria; 193 FN episodes were evaluated and 77 of them were analyzed extensively. Sixty percent of cases were female. Mean age ± standard deviation (SD) was 28.3 ± 14.2 years. The majority of patients had focal (80%) symptomatic (44%) epilepsy. Most patients reported a high ictal frequency (58%) and were on polytherapy (51%). Patients presented psychosis (86.4%), mood disorders (25.8%), and dissociation (4.5%) as the main manifestations. In the psychosis group, persecutory (52.6%) and reference (47.3%) delusions were frequent. FN was provoked by an antiepileptic drug (AED) (48.5%) mainly levetiracetam, epilepsy surgery (31.8%), or vagus nerve stimulation (13.6%). Treatment was homogeneous including anticonvulsant withdrawal (47%) or taper (25%); antipsychotics were initiated in the majority of cases (73%). Psychiatric symptoms were partially controlled in 35%, with complete resolution of symptoms in the remaining 65% of cases. The majority of patients (87%) with AED trigger and withdrawal presented complete resolution of symptoms in comparison to 28.5% of patients triggered by surgery. SIGNIFICANCE: Forced normalization is an entity whose pathophysiology remains uncertain. Antipsychotic drug use does not predict complete resolution of psychiatric symptoms in comparison with AED withdrawal. Although there is a positive response to treatment in patients with FN triggered by drugs, the prognosis is obscure in patients with surgery triggered FN.

The Montreal procedure: The legacy of the great Wilder Penfield.

Wilder Penfield pioneered the early practice of brain surgery. In binding together the disciplines of neurosurgery, neurology, neuropathology, psychology, and related basic sciences, Penfield transformed our understanding of the field of neuroscience. He brought to the operating room the meticulous techniques of Sherrington, combined with methods of stimulation described by Foerster, which he complemented with expert knowledge of the neurocytology of nervous tissue. While developing surgical treatments for epilepsy, Penfield began to map the brain. He established the "Montreal procedure" for the surgical treatment of epilepsy. His scientific contributions on neurostimulation were transformative in their time and continue to resonate today. This article reviews the life of Wilder Penfield and summarizes key scientific contributions. Specifically, we detail the Montreal procedure. We additionally present a painting by Canadian artist Iris Hauser, which purports to display the hidden treasures of the human mind.

Epilepsy, Physical Activity and Sports: A Narrative Review.

People with epilepsy (PWE) are less physically active compared with the general population. Explanations include prejudice, overprotection, unawareness, stigma, fear of seizure induction and lack of knowledge of health professionals. At present, there is no consensus on the role of exercise in epilepsy. This paper reviews the current evidence surrounding the risks and benefits associated with physical activity (PA) in this group of patients. In the last decade, several publications indicate significant benefits in physiological and psychological health parameters, including mood and cognition, physical conditioning, social interaction, quality of life, as well as potential prevention of seizure presentation. Moreover, experimental studies suggest that PA provides mechanisms of neuronal protection, related to biochemical and structural changes including release of ß-endorphins and steroids, which may exert an inhibitory effect on the occurrence of abnormal electrical activity. Epileptic discharges can decrease or disappear during exercise, which may translate into reduced seizure recurrence. In some patients, exercise may precipitate seizures. Available evidence suggests that PA should be encouraged in PWE in order to promote wellbeing and quality of life. There is a need for prospective randomized controlled studies that provide stronger clinical evidence before definitive recommendations can be made.

Update on Minimal Standards for Electroencephalography in Canada: A Review by the Canadian Society of Clinical Neurophysiologists.

Surface electroencephalogram (EEG) recording remains the gold standard for noninvasive assessment of electrical brain activity. It is the most efficient way to diagnose and classify epilepsy syndromes as well as define the localization of the epileptogenic zone. The EEG is useful for management decisions and for establishing prognosis in some types of epilepsy. Electroencephalography is an evolving field in which new methods are being introduced. The Canadian Society of Clinical Neurophysiologists convened an expert panel to develop new national minimal guidelines. A comprehensive evidence review was conducted. This document is organized into 10 sections, including indications, recommendations for trained personnel, EEG yield, paediatric and neonatal EEGs, laboratory minimal standards, requisitions, reports, storage, safety measures, and quality assurance.

Epilepsy through the ages: An artistic point of view.

The historical allure of epilepsy transcends academic circles and serves as fascinating critique of the state of the times-its values, judgments, mythos, and people. Immortalized and laid bare in artistic renderings of epilepsy are societal truths, at times both disparately grandiose and grotesque. During the middle ages and Renaissance, the European discourse on epilepsy assumed religious fervor. Epilepsy was considered a demonic machination and its cure an act of divine intercession. A similar theme is found in the artistic depiction of epilepsy from the Inca and Aztec civilizations of that time. After the 19th century drew to a close, the ascendency of empiricism coincided with waning creative interest in epilepsy, with few paintings or pieces to capture insightful perspectives on the illness. In this paper, we review the relationship between art and epilepsy and present two contemporary paintings that convey current western perceptions. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity".

Tlazolteotl, the Aztec goddess of epilepsy.

Epilepsy has afflicted humanity during most of the extent of documented history. The Aztecs believed that illnesses were punishments that were sent from a furious goddess. In particular, epilepsy was considered in Aztec culture as a "sacred disease", and convulsions were traditionally associated with a deified woman who had died at childbirth. As the goddess Shiva and Apasmâra in ancient India and Saint Valentine in Germany, Tlazolteotl was considered able to bring about and send away epilepsy. We performed a comprehensive review to identify Tlazolteotl depictions and its historical context related with epilepsy. Tlazolteotl is one of the most endearing and complex goddesses of the Mesoamericans. She was the deity of the black fertile and fecund earth that gains its energy from death and in turn feeds life. Associated with purification, expiation, and regeneration, she embodied fertility and turned all garbage, physical and metaphysical, into rich life. This article reviews the most relevant artistic works related with Tlazolteotl. We also present a modern depiction of the Aztec goddess of epilepsy from the Mexican artist Eduardo Urbano Merino, displaying the supernatural view of epilepsy in America.

StatNet Electroencephalogram: A Fast and Reliable Option to Diagnose Nonconvulsive Status Epilepticus in Emergency Setting.

BACKGROUND: The StatNet electrode set is a system that can be applied by a non-electroencephalogram (EEG) technologist after minimal training. The primary objectives of this study are to assess the quality and reliability of the StatNet recordings in comparison to the conventional EEG. METHODS: Over 10 months, 19 patients with suspected nonconvulsive status epilepticus were included from university hospital emergency settings. Each patient received a StatNet EEG by a trained epilepsy fellow and a conventional EEG by registered technologists. We compared the studies in a blinded fashion, for the timeframe from EEG order to the setup time, start of acquisition, amount of artifact, and detection of abnormalities. The nonparametric Mann-Whitney two-sample t test was used for comparisons. The kappa score was used to assess reliability. RESULTS: Mean age of patients was 61±16.3 (25-93) years. The inter-observer agreement for detection of abnormal findings was 0.83 for StatNet and 0.75 for conventional EEG. Nonconvulsive status epilepticus was detected in 10% (2/19) in both studies. The delay from the time of EEG requisition to acquisition was shorter in the StatNet (22.4±2.5 minutes) than the conventional EEG (217.7±44.6 minutes; p<0.0001). The setup time was also shorter in the StatNet (9.9±0.8 minutes) compared with the conventional EEG (17.8±0.8 minutes; p<0.0001). There was no difference in the percentage of artifact duration between the two studies (p=0.89). CONCLUSION: This study demonstrates that StatNet EEG is a practical and reliable tool in the emergency setting, which reduces the delay of testing compared with conventional EEG, without significant compromise of study quality.

Clinical Benefit of 3 Tesla Magnetic Resonance Imaging Rescanning in Patients With Focal Epilepsy and Negative 1.5 Tesla Magnetic Resonance Imaging.

BACKGROUND: Magnetic resonance imaging is an essential tool in the pre-surgical evaluation of patients with drug-resistant epilepsy. OBJECTIVE: Our aim was to assess the value of re-imaging patients with focal drug-resistant epilepsy. METHODS: Thirty patients with negative or non-conclusive 1.5 Tesla magnetic resonance imaging were rescanned with 1.5T and 3T. All of them had previous 1.5 scans with no seizure protocol in a non-specialized center. Two neuroradiologists who were blinded to prior imaging results randomly reviewed the magnetic resonance images. Kappa score was used to assess the reliability. RESULTS: Mean age of patients was 30 (SD ± 11) years. The intra-observer agreement for the first radiologist was 0.74 for 1.5T and 0.71 for 3T. In the second radiologist it was 0.82 and 0.66, respectively. Three lesions (10%) were identified by general radiologists in non-specialized centers using a 1.5T standard protocol. In our center a consensus between two neuroradiologists using epilepsy protocol identified seven lesions (23%) using 1.5T and 10 (33%) using 3T (p < 0.01). In 28% of patients this additional information resulted in a change in clinical management. CONCLUSIONS: 3T magnetic resonance imaging rescanning improves the diagnostic yield in patients with focal epilepsy and previous negative 1.5T magnetic resonance imaging. Use of 3T magnetic resonance imaging, epilepsy protocols, and interpretation by experienced neuroradiologists is highly recommended.

Medicinal marijuana for epilepsy: a case series study.

OBJECTIVE: To describe the social, clinical and use-patterns characteristics of medicinal marijuana use among patients with epilepsy (PWEs). METHODS: Eighteen PWEs with prescriptions for medicinal marijuana from a Canadian adult-epilepsy clinic were included in this study. RESULTS: Eighteen patients had a prescription of medicinal marijuana from a total population of 800 PWEs in our center (2.2%). Mean age of patients was 30±7.4 (19-50) years. Twelve (67%) patients were males. Eleven (61%) patients had drug-resistant epilepsy. Eleven (61%) patients suffered a psychiatric comorbidity and reported the use of illicit substances or heavy alcohol or tobacco consumption. Only two (11%) patients were married; the rest of patients (89%) were single or divorced. The drug use pattern was similar among patients. All patients asked for marijuana permission in the epilepsy clinic. Most (83%) had a previous history of marijuana smoking, with a mean of 6.6±3 (1-15) years. The mean consumption dose was 2.05±1.8 (0.5-8) grams per day. Ten (56%) patients reported withdrawal seizure exacerbation when they stopped the marijuana. Only two patients (11%) reported side effects, and all patients found medicinal marijuana very helpful for seizure control and improvement of mood disorder. CONCLUSIONS: PWEs using medicinal marijuana have a common profile. They are usually young single men with drug-resistant epilepsy and psychiatric comorbidity. Most used marijuana before formal prescription and all believe the drug was effective on their seizure control. Because of the concurrent use of other antiseizure medications, it is complex to estimate the actual effect of marijuana.

Obesity and its association with generalised epilepsy, idiopathic syndrome, and family history of epilepsy.

Aim. Previous studies support the concept that obesity is a common comorbid condition in patients with epilepsy (PWE). In this study, we present the body mass index (BMI) and data from a survey to assess physical activity in a sample of PWE from an epilepsy clinic. Methods. Between June of 2011 and January of 2013, 100 PWE from an adult epilepsy clinic were included. We obtained BMI, waist circumference, and information regarding physical activity using a standardised questionnaire. Clinical, demographic, electrographic, and imaging parameters were collected from charts. Results. Mean age of patients was 40 ± 14 (18-77) years. The BMI distribution was as follows: 2 patients (2%) underweight, 26 (26%) normal weight, 34 (34%) overweight, 25 (25%) obese, and 13 (13%) with morbid obesity. In our study, obesity was defined as having a BMI ≥ 30. We found 38 (38%) patients in this range. There was no difference in the rate of drug-resistant epilepsy between obese and non-obese patients (55 vs. 55%; p=0.05). Leisure time habit was reported in 82% of obese patients and 79% of patients without obesity. Overall, the most frequent activity was walking (70%). Factors associated with obesity were generalised epilepsy (OR: 2.7, 1.1-6.6; p=0.012), idiopathic syndrome (OR: 2.7, 1.04-7; p=0.018), and family history of epilepsy (OR: 6.1, 1.5-24.2; p=0.002). Conclusion. Our study suggests an association between obesity, idiopathic generalised epilepsy, and family history of epilepsy. Our study shows that PWE are physically active and there is no clear relation between exercise and obesity. We could not identify any association between drug-resistant epilepsy and obesity. Absence of direct comparison with a control non-epileptic population; a cross-sectional design not allowing evaluation of a causal association among variables; and reliance on self-reported physical activity are to be considered as limitations of the present study.

Art and epilepsy surgery.

The impact of health and disease has led many artists to depict these themes for thousands of years. Specifically, epilepsy has been the subject of many famous works, likely because of the dramatic and misunderstood nature of the clinical presentation. It often evokes religious and even mythical processes. Epilepsy surgical treatment has revolutionized the care of selected patients and is a relatively recent advance. Epilepsy surgery has been depicted in very few artistic works. The first portrait showing a potential surgical treatment for patients with epilepsy was painted in the 12th century. During the Renaissance, Bosch famously provided artistic commentary on traditional beliefs in "The stone of madness". Several of these works demonstrate a surgeon extracting a stone from a patient's head, at one time believed to be the source of all "folly", including epileptic seizures, psychosis, intellectual disability, depression, and a variety of other illnesses. There are some contemporary art pieces including themes around epilepsy surgery, all of them depicting ancient Inca Empire procedures such as trepanning. This article reviews the most relevant artistic works related with epilepsy surgery and also its historical context at the time the work was produced. We also present a painting from the Mexican artist Eduardo Urbano Merino that represents the patient's journey through refractory epilepsy, investigations, and ultimately recovery. Through this work, the artist intends to communicate hope and reassurance to patients going through this difficult process.

Use of suggestive seizure manipulation methods in the investigation of patients with possible psychogenic nonepileptic seizures-An international ILAE survey.

Video-encephalographic (vEEG) seizure recordings make essential contributions to the differentiation of epilepsy and psychogenic nonepileptic seizures (PNES). The yield of vEEG examinations can be increased through suggestive seizure manipulation (SSM) (ie, activation/provocation/cessation procedures), but its use has raised ethical concerns. In preparation for guidelines on the investigation of patients with PNES, the ILAE PNES Task Force carried out an international survey to investigate practices of and opinions about SSM. An online questionnaire was developed by the ILAE PNES Task Force. Questions were asked at clinical unit or individual respondent level. All ILAE chapters were encouraged to send questionnaires to their members. The survey was open from July 1, 2019, to August 31, 2019. A total of 487 clinicians from 411 units across 94 countries responded. Some form of SSM was used in 296/411 units (72.0%). Over 90% reported the use of verbal suggestion, over 80% the use of activation procedures also capable of eliciting epileptic activity (hyperventilation or photic stimulation). Only 26.3% of units used techniques specifically intended to provoke PNES (eg, saline injection). Fewer than 10% of units had established protocols for SSM, only 20% of units required written patient consent, in 12.2% of units patients received explicitly false information to provoke seizures. Clinicians using SSM tended to perceive no ethical problems, whereas those not using SSM were likely to have ethical concerns about these methods. We conclude that the use of invasive nocebo techniques intended to provoke PNES in diagnostic settings has declined, but SSM is commonly combined with activation procedures also capable of eliciting epileptic activity. While research suggests that openness about the use of PNES-specific nocebo techniques does not reduce diagnostic yield, very few units have suggestion protocols or seek patient consent. This could be addressed through establishing consensus guidance for the practice of SSM.

The Use of Cannabis as a Treatment for Epilepsy in Adult Patients: Are Side Effects a Limitation of Use?

Marijuana is the dried leaves, stems, and flowers of a 1- to 5-m weed originating from Central Asia. The most common varieties are Cannabis sativa and Cannabis indica. It is usually inhaled as smoke but can also be used as a vapor, taken by mouth as a spray, ingested in tea or as butter in baked goods, or in capsule form and used as an oil. Cannabis has been widely used to treat many medical conditions such as multiple sclerosis symptoms, mood disorders, pain, sleep disorders, and seizures among others. Preclinical and clinical studies have been done over the past decade, among them there are few randomized placebo-controlled trials. In the last few years, Cannabis has been proposed as a potential therapy for patients with drug-resistant epilepsy. This review analyzes the best information about the use of cannabis in adult patients, reviewing aspects of efficacy and safety.

Validation of the Status epilepticus severity score (STESS) at high-complexity hospitals in Medellín, Colombia.

PURPOSE: The Status Epilepticus Severity Score (STESS) is one of the most well-known clinical scoring systems to predict mortality in status epilepticus (SE). The objective of this study was to validate STESS in a Colombian population. METHOD: We evaluated historical data of adult patients (age ≥16 years) with a clinical or electroencephalographic diagnosis of SE admitted between 2014 and 2017. Prospectively, we included patients admitted from January to June of 2018. The primary outcome was in-hospital mortality. Receiver operating characteristic (ROC)-analysis, determination of best cutoff values, sensitivity, specificity, and positive and negative likelihood ratios were performed. RESULTS: The sample was 395 patients, with in-hospital mortality of 16.8 %. The area under the ROC curve for STESS was 0.84. A cutoff point of ≥3 produced the highest sensitivity of 84.9 % (95 % CI 73.9 %-92.5 %) and a specificity of 65.7 % (95 % CI 60.2 %-70.8 %), with a positive likelihood ratio of 2.5 and a negative likelihood ratio of 0.2. CONCLUSIONS: STESS is a useful tool to predict mortality in patients with SE. In Medellin, Colombia, a STESS < 3 allows the identification of the patients who survive reliably. Those patients with a score <3 may have a better prognosis, and treatment with fewer side effects than anaesthetics could be suggested, always remembering the importance of the treating physician's clinical judgement.

Risk factors associated with drug resistant focal epilepsy in adults: A case control study.

PURPOSE: Using an adult cohort of patients with focal epilepsy, we aimed to identify risk factors for development of drug-resistant epilepsy, which if identifiable would allow patients to receive appropriate counsel and earlier surgical treatment. METHODS: This is a case-control study nested within a cohort, 146 adult patients with focal epilepsy were included. Definitions were used in accordance with ILAE criteria. The odds ratio and its confidence interval were calculated. We performed a logistic regression analysis. RESULTS: Seventy-one [48.6%] patients met the criteria for drug-resistant epilepsy [cases] and 75 [51.4%] patients were controls. The mean age of patients was 44.5 ± 16.4 years. The most significant variables associated with developing drug-resistant epilepsy include younger age at diagnosis [18.75 vs. 32.2, p < 0.001], years of evolution of epilepsy [22.54 vs. 16.05, p < 0.001], number of AED [4.8 vs. 2.87, p < 0.001], complex partial seizures [51 vs. 35 OR 2.9, p = 0.002], having more than one seizure per month [51 vs. 38, p = 0.009], bi-temporal focus [14 vs. 4 p = 0.008] and mesial temporal sclerosis [23 vs. 11 p = 0.01]. Good response to first AED [7 vs. 29 OR 0.2, p = 0.001] and epilepsy secondary to encephalomalacia [8 vs. 20 OR 0.35, p = 0.018] might be protective factors against drug resistant epilepsy. CONCLUSIONS: Longer time of epilepsy evolution, high frequency of seizures, complex partial seizure presentation, higher number of antiepileptic drugs, mesial temporal sclerosis and bitemporal epilepsy are predictive factors of subsequent pharmacoresistance.

Forced normalization after turning off vagus nerve stimulation in Lennox-Gastaut syndrome.

Forced normalization is the development of psychiatric symptoms in a patient experiencing remission of seizures. We present a case of Lennox Gastaut syndrome in which forced normalization developed after vagus nerve stimulation was stopped. The patient had drug resistant epilepsy and failed anti-seizure drugs, vagus nerve stimulation, and a partial callosotomy. The patient had multiple types of seizures including drop attacks, absences, and tonic-clonic seizures. He tried vagus nerve stimulation for two years without success. Forced normalization developed after the vagus nerve stimulator was turned off. This is the first case to our knowledge to describe forced normalization after turning off the vagus nerve stimulator.