A pilot randomized controlled clinical trial of Transcranial Alternating Current Stimulation in patients with multifocal pharmaco-resistant epilepsy.

Transcranial Alternating Current Stimulation (tACS) is a promising noninvasive electrical stimulation therapy for neuropsychiatric diseases. Invasive neuromodulation using alternating current has been efficacious for drug-resistant epilepsy, but it is associated with surgical and medical complications. We aimed to explore the safeness and effectivity on seizure frequency reduction of two tACS protocols against placebo in patients with multifocal refractory epilepsy. This was a randomized, double-blinded, placebo-controlled clinical trial with 3-arm parallel-group (placebo, 30 min/2 mA daily sessions for 3 days [tACS-30], and 60 min/2 mA weekday sessions [tACS-60]). The main outcome was considered a change in reducing seizure frequency at 2 months after the intervention. Secondary outcomes were the apparition of any adverse effects during follow-up. At the second month, we observed a nonsignificant reduction in the seizure frequency in the placebo (7.3 ±â€¯40.4%, p > 0.05) and the tACS-60 (26 ±â€¯37.7%, p > 0.05). While the tACS-30 group showed a nonsignificant increase in seizure frequency (63.6 ±â€¯155.3%, p > 0.05). No changes were statistically different from the placebo group. Otherwise, participants experienced only minor adverse events - the most common being an initial local transient tingling sensation (21%). This pilot study of tACS raises no severe safety issues, but provides negligible evidence for efficacy using this brief treatment protocol. Therefore, more studies are warranted testing different parameters to further verify the safety and effectivity of tACS in multifocal epilepsy.

Prevalence of epilepsy, beliefs and attitudes in a rural community in Mexico: A door-to-door survey.

OBJECTIVE: The study aimed to establish the prevalence of seizure history (SH) and epilepsy in a rural community in Hidalgo, Mexico and determine the patients' beliefs and attitudes towards the disease and its initial medical treatment. METHODOLOGY: A transverse, descriptive, door-to-door epidemiological study (April 2011-November 2012) was conducted with 863 inhabitants from Xocotitla, Huejutla, Hidalgo, Mexico (162 housing units). Patients with SH were identified with an adaptation of the WHO protocol for epidemiological studies of neurological diseases. Afterwards, the subjects identified with seizure history (SH) or epilepsy were interviewed with a 20-question Likert type questionnaire regarding the management and belief set of their SH. The interviews were conducted in Spanish and Nahuatl. RESULTS: The prevalence of epilepsy and isolated nonrecurring seizures was 38.2/1000 and 25.4/1000, respectively. Out of the total population of 863 inhabitants, 33/863 were identified with SH: only 39.3% were able to identify an epileptic seizure as such, 48.5% sought medical attention upon the first seizure, 33.3% used a traditional healer, 15.2% took no action, 3% sought a religious representative, 85% lacked any lab analysis, and 60% received no antiepileptic drugs. Only 39% received free local medical attention, 69.7% considered seizures and epilepsy to be a consequence of divine intervention, and 94% reported some type of discrimination. CONCLUSIONS: A high prevalence of epilepsy and SH was found in this rural community in Mexico. Divine/religious beliefs, discrimination, scarce access to basic health services and inadequate medical management of epilepsy and SH persist.

Utility of electrocorticography in the surgical treatment of cavernomas presenting with pharmacoresistant epilepsy.

AIM: To describe the general aspects of cavernomas and epilepsy and review the available literature on the utility of electrocorticography (ECoG) in cerebral cavernoma surgery. METHODS: We searched studies in PubMed, MedLine, Scopus, Web of Science, and Google Scholar (from January 1969 to December 2013) using the keywords "electrocorticography" or "ECoG" or "prognosis" or "outcome" and "cavernomas". Original articles that reported utility of ECoG in epilepsy surgery were included. Four review authors independently selected the studies, extracted data, and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines, and Jadad Scale. A meta-analysis was not possible due to methodological, clinical, and statistical heterogeneity of included studies. We analysed six articles with a total of 219 patients. RESULTS: The most common surgical approach was lesionectomy using ECoG in the temporal lobe with Engel I outcome range from 72.7 to 100%. CONCLUSIONS: Small controlled studies suggest that ECoG-guided resection offers the best functional results in seizure control for subjects undergoing cavernoma surgery, especially in the temporal lobe.

Nonconvulsive Status Epilepticus: Clinical Findings, EEG Features, and Prognosis in a Developing Country, Mexico.

PURPOSE: There is a lack of clinical and epidemiological knowledge about nonconvulsive status epilepticus (NCSE) in developing countries including Mexico, which has the highest prevalence of epilepsy in the Americas. Our aim was to describe the clinical findings, EEG features, and outcomes of NCSE in a tertiary center in Mexico. METHODS: We conducted a retrospective case series study (2010-2020) including patients (≥15 years old) with NCSE according to the modified Salzburg NCSE criteria 2015 with at least 6 months of follow-up. We extracted the clinical data (age, sex, history of epilepsy, antiseizure medications, clinical manifestations, triggers, and etiology), EEG patterns of NCSE, and outcome. Descriptive statistics and multinomial logistic regression were used. RESULTS: One hundred thirty-four patients were analyzed; 74 (54.8%) women, the total mean age was 39.5 (15-85) years, and 71% had a history of epilepsy. Altered state of consciousness was found in 82% (including 27.7% in coma). A generalized NCSE pattern was the most common (32.1%). The NCSE etiology was mainly idiopathic (56%), and previous uncontrolled epilepsy was the trigger in 48% of patients. The clinical outcome was remission with clinical improvement in 54.5%. Multinomial logistic regression showed that the patient's age (P = 0.04), absence of comorbidities (P = 0.04), history of perinatal hypoxia (P = 0.04), absence of clinical manifestations (P = 0.01), and coma (P = 0.03) were negatively correlated with the outcome and only the absence of generalized slowing in the EEG (P = 0.001) had a significant positive effect on the prognosis. CONCLUSIONS: Age, history of perinatal hypoxia, coma, and focal ictal EEG pattern influence negatively the prognosis of NCSE.

The double generalization phenomenon in juvenile absence epilepsy.

The characterization of a seizure as generalized or focal onset depends on a basic knowledge of the underlying pathophysiology. Recently, an uncommon phenomenon in generalized epilepsy-evolution of seizures from generalized to focal followed by secondary generalization-was reported for the first time. We describe a 15-year-old boy, initially classified as having partial epilepsy, who had a typical absence seizure that became focal with second secondary generalization (double generalization). On the basis of these findings his epilepsy was classified as juvenile absence epilepsy and his treatment was changed, resulting in seizure freedom. This is the first report of this unusual electroclinical evolution in a patient with juvenile absence epilepsy. The recognition of this particular pattern allows correct classification and impacts both treatment and prognosis.

Neurophysiological Intraoperative Monitoring in the Elderly.

INTRODUCTION: Intraoperative neurophysiological monitoring (IONM) is widely used to prevent nervous system injury during surgeries in elderly patients. However, there are no studies that describe the characteristics and changes in neurophysiological tests during the IONM of patients aged 60 years and older. The study aims to describe and compare IONM changes during surgeries in adult patients aged 18 to 59 years with those aged 60 years and older. METHODS: We performed a comparative retrospective study of patients aged 18 to 59 years versus those 60 aged years and older who underwent IONM during 2013 to 2018 in Mexico City. Sociodemographic characteristics were recorded and compared. Intraoperative neurophysiological monitoring techniques, their changes, and surgical procedures for both groups were analyzed and compared using descriptive statistics, Mann-Whitney U, Fisher, and χ2 tests. The sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: In total, 195 patients were analyzed: 104 patients, 68.63 ± 6.54 years old (elderly group) and 91 patients, 42.3 ± 10.5 years old (younger group). No differences were found in the rates of signal change during IONM between the group of elderly patients and the younger group. The sensitivity, specificity, and positive and negative predictive values were 80%, 99%, 80%, and 99%, respectively. CONCLUSIONS: Elderly patients have a similar rate of changes in IONM signals compared with younger patients during heterogeneous surgeries guided by IONM.

Microbeam radiosurgery using synchrotron-generated submillimetric beams: a new tool for the treatment of brain disorders.

Since its advent during the mid-twentieth century, radiosurgery has undergone a steady evolution. Gamma Knife and linear accelerator based systems using rigid frames preceded the development of frameless devices. The present report describes the development of microbeam radiosurgery, a technique which uses submillimetric beams of radiation to treat disease. Typically, the technique is employed using parallel arrays of beams delivered via a high-fluence synchrotron source. Beam widths between 20 and 950 µm have been used with the majority of studies utilizing beam widths less than 100 µm. In addition to its high precision, the technique allows users to take advantage of two unique properties of microbeams. The first is a remarkable tolerance of healthy tissue to microbeams delivered at doses up to several hundred grays, while at the same time, tumors are highly susceptible to the lethal effects of microbeams. Together, these findings allow for a "preferential tumoricidal effect" beyond the typical dose-volume relationship. Although only used in animal experiments so far, we explore the hypothetical clinical role of microbeam radiosurgery which may be feasible in the near future. In addition to the treatment of traditional radiosurgery targets such as malignancies and vascular malformations, microbeams may allow the non-invasive treatment of functional disease such as movement disorders, epilepsy, and mental illness.

Effects of resective epilepsy surgery on the social determinants of health.

OBJECTIVES: The aim of this study is to analyze changes in the Social Determinants of Health (SDH) in patients undergoing epilepsy surgery in Mexico. MATERIALS AND METHODS: We retrospectively analyzed 102 adult patients who underwent brain resection for focal epilepsy (2002-2014) with at least 4 years of follow-up; described clinical variables (age, race, sex, age of onset of epilepsy, age at the time of surgery, type of surgery, side of surgery) and sociodemographic variables including education, income, race/ethnicity, occupation, and marital status. STATISTICAL ANALYSIS: Descriptive and inferential statistics were used. RESULTS: 54.9% (56) of the participants were women, with a mean age of 38.2 (±9.6) years at the time of the survey. The average and mean duration of drug-resistant epilepsy before surgery after diagnosis was 19.6 (±9.3) years; 77.9% (77) had temporal lobe surgeries and 24.5% (25) had extra-temporal lobe surgeries; 80.4% (82) and 19.6% (20) of patients were classified as Engel I and Engel II, respectively, with at least 4 years of postoperative follow-up. Education level (26.9%, p=<0.001), employment rate (4.9%, p= <0.001), and income (9.8%, p = 0.024) increased after surgery; 20.5% of patients were married after surgery. CONCLUSIONS: Following focal resective epilepsy surgery there was a significant increase in the education level, financial income and employment at 4 years' postoperative follow-up.

Pediatric Montages in Clinical Practice.

The montages in clinical EEG recordings in neonates, infants, and children follow some basic principles of adolescent or adult EEG recordings; however, special considerations are needed to obtain optimal diagnostic yield in pediatric patients. The aim of this review is to summarize the pediatric montages recommended in clinical practice in the standard clinical neurophysiology laboratory and in special situations.

Neuromodulation techniques for status epilepticus: A review.

BACKGROUND: Electroconvulsive therapy (ECT), Vagal Nerve Stimulation (VNS), Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS) are neuromodulation therapies that have been used to treat Status Epilepticus (SE). OBJECTIVE: Review the literature about the efficacy and safety of neuromodulation therapies in SE in humans. METHODS: We searched studies in PubMed, Scopus, Google Scholar and Science Direct (inception to June 2018). Four review authors independently selected the studies, extracted data and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines, Oxford and GRADE scales, and Murad et al., 2018 methodological quality and synthesis of case series and case reports. RESULTS: We analyzed 27 articles (45 patients) with 4 different neuromodulation therapies. In ECT we found 80% rate of disruption of SE and 5% of adverse events was reported. Using iVNS 15/16 (93.7%) patients resolved the SE. All patients who underwent TMS and DBS aborted SE, however, 50% of patients with DBS had severe adverse events. CONCLUSIONS: Case series and case reports suggest that neuromodulation therapies can abort SE in 80-100% of patients (Oxford scale and GRADE were level 4 and D) with a wide range of adverse effects, which claims for prospective studies on the relationship be-tween efficacy and safety.

Neurosurgical Therapy for Status Epilepticus in Oligoastrocytoma Patients.

BACKGROUND: Super-refractory status epilepticus (SRSE) is a life-threatening neurologic emergency defined as "status epilepticus (SE) that continues 24 hours or more after the onset of anesthesia, including those cases in which the SE recurs on the reduction or withdrawal of anesthesia," which occurs in 10% to 15% of patients with SE and rarely has been resolved surgically. CASE DESCRIPTIONS: A 20-year-old man with SRSE and a long history of left parieto-occipital oligoastrocytoma was admitted for convulsive SE that became SRSE and underwent lesionectomy guided by electrocorticography and neuronavigation for local tumor recurrence. Histopathologic diagnosis was oligoastrocytoma. SRSE was aborted and the patient recovered fully without any functional deficits. CONCLUSIONS: The lesionectomy guided by electrocorticography and neuronavigation should be considered as a treatment option for patients with SRSE.

Successful intraoperative spinal cord monitoring during scoliosis surgery using a total intravenous anesthetic regimen including dexmedetomidine.

Intraoperative neurophysiological monitoring (IONM) during corrective spinal surgery is widely used. Because of the possible interference with the recording of evoked potentials by inhalational anesthetics, total intravenous anesthetic (TIVA) regimens have been advocated. TIVA regimens may be difficult to use in pediatric populations due to metabolic factors. We report on the results of multimodality IONM during 18 cases in which a TIVA regimen incorporating dexmedetomidine (Precedex, Hespira, Lake Forest, IL) was used. Monitoring techniques included sensory (SSEP) and motor evoked potentials (MEP), as well as pedicle screw stimulation. SSEPs were maintained within an acceptable range of baseline amplitude (50%) and latency (10%), and MEPs remained elicitable throughout each case. We therefore found that the anesthetic regimen did not significantly interfere with any of the monitoring modalities used and conclude that IONM in the presence of dexmedetomidine is feasible under appropriate conditions.

Dynamic changes of the intraocular pressure and the pressure of cerebrospinal fluid in nonglaucomatous neurological patients.

PURPOSE: To describe the dynamic changes of the intraocular pressure (IOP) and intracranial pressure (ICP) with normal or pathological values (intracranial hypertension) in nonglaucomatous neurological patients during lumbar punction (LP). METHODS: Case-control study, prospective measurement of tonometry in both groups referred for LP. Intraocular pressure, ICP and translaminar pressure difference (TPD) were compared pre- and post-LP. RESULTS: Thirty-six patients (72 eyes) with mean age of 38.5 (16-64) years and BMI of 26.81 kg/m2 were analysed. The initial mean ICP was 12.81 (± 6.6) mmHg. The mean TPD before and after the LP was 1.48 mmHg and 0.65 mmHg, respectively. The mean IOP of both eyes decreased to 0.8 mmHg post-LP in patients with pathological ICP (p = 0.0193) and normal ICP (p = 0.006). CONCLUSIONS: We found a statistically significant decrease of the IOP post-LP compared to the pre-LP in both groups, being higher in patients with pathological ICP. There were no significant differences of the IOP in patients with normal versus pathological ICP pre-LP/post-LP; neither was found a correlation between ICP and IOP.

Transcranial Direct Current Stimulation in Mesial Temporal Lobe Epilepsy and Hippocampal Sclerosis.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been evaluated in medication refractory epilepsy patients. The results have been inconclusive and protocols have varied between studies. OBJECTIVE: To evaluate the safety and efficacy of two protocols of tDCS in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). METHODS: This is a randomized placebo-controlled, double-blinded clinical trial, with 3 arms, 3 sessions, 5 sessions and placebo stimulation. Frequency of seizures (SZs), interictal epileptiform discharges (IEDs) and adverse effects (AEs) were registered before and after treatment, and at 30 and 60 days follow-up. Descriptive statistics, k-related samples, Friedman's test, and relative risk (RR) estimation were used for analysis. RESULTS: We included twenty-eight subjects (3d n = 12, 5d n = 8, placebo n = 8), 16/28 (57%) men, age 37.8(±10.9) years old. There was a significant reduction of the frequency of SZs at one (p = 0.001) and two (p = 0.0001) months following cathodal tDCS compared to baseline in the 3 arms (p = 0.0001). The mean reduction of SZ frequency at two months in both active groups was significantly higher than placebo (-48% vs. -6.25%, p < 0.008). At 3 days (-43.4% vs. -6.25%, p < 0.007) and 5 days (-54.6% vs. -6.25%, p < 0.010) individual groups showed a greater reduction of SZs. A significant IED reduction effect was found between baseline and immediately after interventions (p = 0.041) in all groups. Side effects were minor. CONCLUSIONS: Cathodal tDCS technique of 3 and 5 sessions decreased the frequency of SZs and IEDs (between baseline and immediately post-tDCS) in adult patients with MTLE-HS compared to placebo tDCS.

Radiosurgery for epilepsy.

Radiosurgery is an emerging therapeutic approach for the treatment of medically intractable epileptogenic foci. A favourable seizure outcome was first reported in studies of the effects of radiosurgery in the treatment of arteriovenous malformations and tumours. Radiosurgery has since been applied to the treatment of complex partial seizures with mesial-temporal-lobe onset. Nearly simultaneously, experimental evidence supporting the usefulness of radiosurgery to improve or abolish seizures has confirmed that stereotactic irradiation can preferentially affect epileptogenic versus normal cortex. Further work is clearly needed, but this technique might become an important approach in the management of mesial-temporal and extratemporal epilepsy, especially if refractory seizures arise from eloquent cortex or surgically challenging regions of brain.

Transcranial Direct Current Stimulation in Epilepsy.

BACKGROUND: Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation therapy in epilepsy with conflicting results in terms of efficacy and safety. OBJECTIVE: Review the literature about the efficacy and safety of tDCS in epilepsy in humans and animals. METHODS: We searched studies in PubMed, MedLine, Scopus, Web of Science and Google Scholar (January 1969 to October 2013) using the keywords 'transcranial direct current stimulation' or 'tDCS' or 'brain polarization' or 'galvanic stimulation' and 'epilepsy' in animals and humans. Original articles that reported tDCS safety and efficacy in epileptic animals or humans were included. Four review authors independently selected the studies, extracted data and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines and Jadad Scale. A meta-analysis was not possible due to methodological, clinical and statistical heterogeneity of included studies. RESULTS: We analyzed 9 articles with different methodologies (3 animals/6 humans) with a total of 174 stimulated individuals; 109 animals and 65 humans. In vivo and in vitro animal studies showed that direct current stimulation can successfully induce suppression of epileptiform activity without neurological injury and 4/6 (67%) clinical studies showed an effective decrease in epileptic seizures and 5/6 (83%) reduction of inter-ictal epileptiform activity. All patients tolerated tDCS well. CONCLUSIONS: tDCS trials have demonstrated preliminary safety and efficacy in animals and patients with epilepsy. Further larger studies are needed to define the best stimulation protocols and long-term follow-up.

Diazepam prophylaxis for bicuculline-induced seizures: a rat dose-response model.

We developed a screening methodology to test the ability of putative antiepileptic drugs delivered directly to a seizure focus to prevent epileptiform activity. The left hippocampi of 15 rats were implanted with an injection cannula and bipolar recording electrodes. Bone screws were used to record neocortical EEG activity. Diazepam (DZP) at one of four possible concentrations or control solution was injected into the hippocampus, followed 5 min later by bicuculline methiodide. DZP suppressed spikes and ictal events in a dose-dependent manner (P<0.0001). At 100 mM, DZP reduced spikes from 678+/-128 to 87+/-35 for a 15 min segment. Numbers of ictal events (seizure) and latency to the first event were reduced by prophylactic DZP. The study establishes a protocol for testing of intracranially-injected drugs to prevent focal seizures.

Anti-kindling effect of slow repetitive transcranial magnetic stimulation in rats.

The cerebrospinal fluid (CSF) of animals exposed to electroconvulsive shock (ECS) has anticonvulsant properties when injected into naive animals. The present study investigated whether the CSF of humans exposed to 1 or 10 Hz repetitive transcranial magnetic stimulation (rTMS) has similar properties. Using a 4 day rat flurothyl kindling seizure model we found that the kindling rate was significantly decreased by intraventricular injection of CSF from depressed patients exposed to 1 Hz rTMS. The CSF from patients that underwent 10 Hz rTMS showed a trend toward an increased kindling rate. These results support the similarity of ECS and rTMS and suggest that 1 Hz and 10 Hz rTMS produce distinct physiologic changes.