Seizure Therapy Research Articles

Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST): protocol for identification of novel biomarkers via neurophysiology

BackgroundElectroconvulsive therapy (ECT) is the most effective treatment for treatment-resistant depression (TRD), especially for acute suicidal ideation, but the associated cognitive adverse effects and negative stigma limit its use. Another seizure therapy under development is magnetic seizure therapy (MST), which could potentially overcome the restrictions associated with ECT with similar efficacy. The neurophysiological targets and mechanisms of seizure therapy, however, remain poorly understood.Methods/designThis neurophysiological study protocol is published as a companion to the overall Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST) protocol that describes our two-site, double-blind, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. Our aim for the neurophysiological component of the study is to evaluate two biomarkers, one to predict remission of suicidal ideation (primary outcome) and the other to predict cognitive impairment (secondary outcome). Suicidal ideation will be assessed through cortical inhibition, which according to our preliminary studies, correlates with remission of suicidal ideation. Cortical inhibition will be measured with simultaneous transcranial magnetic stimulation (TMS) and electroencephalography (EEG), TMS-EEG, which measures TMS-evoked EEG activity. Cognitive adverse effects associated with seizure therapy, on the contrary, will be evaluated via multiscale entropy analysis reflecting the complexity of ongoing resting-state EEG activity.DiscussionECT and MST are known to influence cortical inhibition associated with depression, suicidal ideation severity, and clinical outcome. Therefore, evaluating cortical inhibition and brain temporal dynamics will help understand the pathophysiology of depression and suicidal ideation and define new biological targets that could aid clinicians in diagnosing and selecting treatments. Resting-state EEG complexity was previously associated with the degree of cognitive side effects after a seizure therapy. This neurophysiological metric may help clinicians assess the risk for adverse effects caused by these useful and effective treatments.Trial registrationClinicalTrials.govNCT03191058. Registered on June 19, 2017.

Magnetic Seizure Therapy Compared to Electroconvulsive Therapy for Schizophrenia: A Randomized Controlled Trial.

Background: Magnetic seizure therapy (MST) is a potential alternative to electroconvulsive therapy (ECT). However, reports on the use of MST for patients with schizophrenia, particularly in developing countries, which is a main indication for ECT, are limited.Methods: From February 2017 to July 2018, 79 inpatients who met the DSM-5 criteria for schizophrenia were randomized to receive 10 sessions of MST (43 inpatients) or ECT (36 inpatients) over the course of 4 weeks. At baseline and 4-week follow-up, the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to assess symptom severity and cognitive functions, respectively.Results: Seventy-one patients who completed at least half of the treatment protocol were included in the per-protocol analysis. MST generated a non-significant larger antipsychotic effect in terms of a reduction in PANSS total score [g = 0.17, 95% confidence interval (CI) = −0.30, 0.63] and response rate [relative risk (RR) = 1.41, 95% CI = 0.83–2.39]. Twenty-four participants failed to complete the cognitive assessment as a result of severe psychotic symptoms. MST showed significant less cognitive impairment over ECT in terms of immediate memory (g = 1.26, 95% CI = 0.63–1.89), language function (g =1.14, 95% CI = 0.52–1.76), delayed memory (g = 0.75, 95% CI = 0.16–1.35), and global cognitive function (g = 1.07, 95% CI = 0.45–1.68). The intention-to-treat analysis generated similar results except for the differences in delayed memory became statistically insignificant. Better baseline cognitive performance predicted MST and ECT response.Conclusions: Compared to bitemporal ECT with brief pulses and age-dose method, MST had similar antipsychotic efficacy with fewer cognitive impairments, indicating that MST is a promising alternative to ECT as an add-on treatment for schizophrenia.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT02746965.

Pharmacological and somatic treatment effects on suicide in adults: A systematic review and meta-analysis.

Suicide is a public health crisis. We conducted a systematic review and meta-analysis of the effects of psychopharmacologic and somatic therapies on suicide risk. A systematic search of MEDLINE for studies evaluating the effects of pharmacologic (excluding antidepressants) or somatic interventions on suicide risk was conducted. Studies were included if they used a comparison group, reported on suicide death, assessed a psychopharmacological or somatic intervention, and included adults. Study quality was assessed using the Newcastle-Ottawa scale. Fifty-seven studies were included from 2940 reviewed citations. In bipolar disorder, lithium was associated with a reduction in the odds of suicide compared to active controls (odds ratio [OR] = .58, p = .005; k = 12) and compared to placebo/no lithium (OR = .46, p = .009; k = 9). In mixed diagnostic samples, lithium was associated with a reduction in the odds of suicide compared to placebo/no lithium (OR = .27, p < .001; k = 12), but not compared to active controls (OR = .89, p = .468; k = 7). In psychotic disorders, clozapine was associated with a reduction in the odds of suicide (OR = .46, p = .007; k = 7). Associations between suicide death and electroconvulsive therapy(OR = .77, p = .053; k = 11), non-clozapine antipsychotics in bipolar disorder (OR = .73, p = .090; k = 6) and antipsychotics in psychotic disorders (OR = .39, p = .069; k = 6) were not significant. There was no consistent relationship between antiepileptic mood stabilizers and suicide. There were insufficient studies to meta-analyze associations of suicide risk with vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, or transcranial direct current stimulation. Lithium and clozapine have consistent data supporting protective effects against suicide in certain clinical contexts.

Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST): study protocol for a randomized non-inferiority trial of magnetic seizure therapy versus electroconvulsive therapy

BackgroundElectroconvulsive therapy (ECT) is well-established and effective for treatment-resistant depression (TRD), but in Canada and the USA, less than 1% of patients with TRD receive ECT mainly due to its cognitive adverse effects (i.e. amnesia). Thus, new treatment alternatives for TRD are urgently needed. One such treatment is magnetic seizure therapy (MST). ECT involves applying a train of high-frequency electrical stimuli to induce a seizure, whereas MST involves applying a train of high-frequency magnetic stimuli to induce a seizure.MethodsIn this manuscript, we introduce our international, two-site, double-blinded, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. This trial will compare the efficacy of MST to right unilateral ultra-brief pulse width electroconvulsive therapy (RUL-UB-ECT) with a combined primary endpoint of remission of depression and superior cognitive adverse effects in 260 patients with TRD. Amelioration of suicidal ideation will be assessed as a secondary endpoint. Inpatients or outpatients, over 18 years of age with a MINI International Neuropsychiatric Interview (MINI) diagnosis of non-psychotic major depressive disorder (MDD) can be enrolled in the study provided that they meet illness severity and full eligibility criteria. Participants are randomized to receive MST or RUL-UB ECT, 2-3 days per week over seven weeks, or a maximum of 21 treatments. The study will involve before-, during-, and after-treatment assessments of depression severity, suicidal ideation, subjective side-effects, and cognitive performance consistent with an intent-to-treat study design approach.DiscussionPositive results from this trial could have an immediate and tremendous impact for patients with TRD. If MST demonstrates comparable antidepressant treatment efficacy to ECT, but with greater cognitive safety, it could rapidly be adopted into clinical practice. Indeed, given that the administration of MST is nearly identical to ECT, the majority of ECT facilities in North America could readily adopt MST. Furthermore, the potential for cognitive safety could lead to improved treatment acceptability. Healthcare providers, patients and care partners, and policymakers would therefore demand this form of convulsive therapy.Trial statusEnrollment for this study began on June 26, 2018, and is estimated to complete recruitment by July 2024. At the time of submission, we have enrolled and randomized 117 participants.Trial registrationClinicalTrials.gov NCT03191058, Registered on June 19, 2017.Primary sponsor:Daniel Blumberger (DMB), Principal InvestigatorDaniel.Blumberger@camh.ca, 416-535-8501 x 33662Contact for public queries: DMB, Daniel.Blumberger@camh.caContact for scientific queries: ZJD, Zdaskalakis@health.ucsd.edu

What’s new with the oldest form of brain stimulation: Innovations in ECT

Abstract The practice of electroconvulsive therapy (ECT) continues to evolve. Changes in the nature of electrical stimulation and in intracerebral current paths have markedly reduced or eliminated ECT’s adverse cognitive side effects, while maintaining its effectiveness. Further improvements in the nature of electrical stimulation will likely involve titrating in the current domain to minimize individual differences in intracranial current density. Improvements in spatial targeting, using magnetic seizure therapy (MST) or focal electrically administered seizure therapy (FEAST), promise to further dissociate therapeutic and adverse effects, and are presently undergoing pivotal trials. The key clinical challenges facing ECT pertain to two issues: when and how to change ECT treatment technique in patients who show inadequate or slow benefit, and optimal methods for enhancing durability of benefit and reducing relapse risk. New research suggests that ECT is routinely terminated prematurely in many depressed patients resulting in unnecessarily reduced remission rates. It will be suggested that there has been a secular shift in ECT practice, where the modal patient currently receives considerably more treatments than in the past. In recent years, it has been demonstrated that ECT results acutely in widespread increases in grey matter volume. The implications of these findings will be briefly discussed. Keywords: electroconvulsive therapy, FEAST, MST, depression

Treatment of epilepsy associated with primary and metastatic brain tumors

There is a number of unsolved issues in management of epilepsy associated with primary and metastatic brain tumors (BTs). In particular, no consensus approaches to treatment of patients with epilepsy associated with BTs have been proposed regarding use of current anti-epileptic drugs (AEDs). The review presents the relevant data on epidemiology, features of clinically manifested epilepsy at varying stages of BTs, aspects of drug-drug interaction between AEDs and anti-tumor agents, AED-related effects on cognitive functions as well as quality of life in patients with epilepsy associated with BTs. Levetiracetam and valproic acid comprise the first-line drugs for treating seizures in patients with BTs. It is unreasonable to use AEDs acting as hepatic microsomal enzyme inducers for therapy of epileptic seizures in BTs, because it may decrease efficacy of chemotherapy agents and glucocorticoids along with elevated rate of side effects. Perampanel acting as a selective noncompetitive AMPA receptor antagonist, may be one of the drugs of choice for the adjunctive therapy of epileptic seizures associated with BTs.

Seizure Management in the Intensive Care Unit.

Purpose of this reviewThis review presents current therapy for seizures in the intensive care unit. The reader is provided with recent evidence regarding the use of EEG in determining treatment for acute seizures. Proposed treatment approaches for seizures and status epilepticus are provided. Controversies and complexity of selecting treatments are discussed.Recent findingsCritical Care EEG Monitoring Research Consortium analyzed the association of periodic and rhythmic electroencephalographic patterns with seizures and found that lateralized and generalized periodic discharges and lateralized rhythmic delta were associated with increased seizure risk. Applications using modified EEG techniques have demonstrated more rapid feedback to the ICU than was previously possible.SummaryAccurate diagnosis and efficient treatment of seizures in the ICU is challenging due to patient factors, complexities of antiepileptic drug therapy, and the required expertise for EEG interpretation. Selection of optimally effective therapy for seizures or status epilepticus depends on multiple factors, making collaboration between neurophysiologists and the ICU team of paramount importance.

Ampa study (a mirroring clinical practice study of perampanel in adults and adolescents) design: Real-world prospective study of perampanel as add-on therapy for focal-onset seizures

Perampanel is a once-daily oral anti-seizure medication (ASM) for focal-onset seizures (FOS) and generalized tonic-clonic seizures. The AMPA Study (501; NCT04257604) was a multicenter, prospective, observational study conducted in Italy to assess the effectiveness and safety of perampanel received as add-on therapy in patients aged ≥12 years with FOS in a real-world setting. We present the design of the AMPA Study.

Multiday cycles of heart rate are associated with seizure likelihood: An observational cohort study.

BackgroundCircadian and multiday rhythms are found across many biological systems, including cardiology, endocrinology, neurology, and immunology. In people with epilepsy, epileptic brain activity and seizure occurrence have been found to follow circadian, weekly, and monthly rhythms. Understanding the relationship between these cycles of brain excitability and other physiological systems can provide new insight into the causes of multiday cycles. The brain-heart link has previously been considered in epilepsy research, with potential implications for seizure forecasting, therapy, and mortality (i.e., sudden unexpected death in epilepsy).MethodsWe report the results from a non-interventional, observational cohort study, Tracking Seizure Cycles. This study sought to examine multiday cycles of heart rate and seizures in adults with diagnosed uncontrolled epilepsy (N=31) and healthy adult controls (N=15) using wearable smartwatches and mobile seizure diaries over at least four months (M=12.0, SD=5.9; control M=10.6, SD=6.4). Cycles in heart rate were detected using a continuous wavelet transform. Relationships between heart rate cycles and seizure occurrence were measured from the distributions of seizure likelihood with respect to underlying cycle phase.FindingsHeart rate cycles were found in all 46 participants (people with epilepsy and healthy controls), with circadian (N=46), about-weekly (N=25) and about-monthly (N=13) rhythms being the most prevalent. Of the participants with epilepsy, 19 people had at least 20 reported seizures, and 10 of these had seizures significantly phase locked to their multiday heart rate cycles.InterpretationHeart rate cycles showed similarities to multiday epileptic rhythms and may be comodulated with seizure likelihood. The relationship between heart rate and seizures is relevant for epilepsy therapy, including seizure forecasting, and may also have implications for cardiovascular disease. More broadly, understanding the link between multiday cycles in the heart and brain can shed new light on endogenous physiological rhythms in humans.FundingThis research received funding from the Australian Government National Health and Medical Research Council (investigator grant 1178220), the Australian Government BioMedTech Horizons program, and the Epilepsy Foundation of America's ‘My Seizure Gauge’ grant.

DRESS SYNDROME

TOPIC: Allergy and Airway TYPE: Global Case Reports INTRODUCTION: Severe cutaneous adverse reactions (SCARs) are a group of disorders caused by a drug-induced hypersensitivity response. One important type of SCAR is Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) – a complex, multisystem, and possibly life-threatening drug response. Here we report a case of Lamictal associated DRESS which is rare and seldom reported. CASE PRESENTATION: A 44-year-old Caucasian female with past medical history significant for COPD on 3 liters home oxygen, bipolar disorder, recurrent mucocutaneous infections and seizures. She has been on Lamictal for treatment of seizures. Patient over last 2 years was admitted in hospital about 5 times with episodes of cough, wheezing and sob. she also had recurrent cutaneous abcesses. Her physician exam was consistent with middle aged female, with diffuse wheezing and skin lesions. Her historical chest x-ray has shown ongoing lll infiltrates, and so it was confirmed with cat scan showing diffuse GGO infiltrates more in left lower lobe. she was investigated with hypersensitivity pneumonitis panel, fungal serology, strep, legionella antigen which was negative. she had slightly lower IGG level. She kept on having these episodes inspire of optimal therapy . Only notable abnormal findings in her laboratory was elevated eosinophils count, with normal IGE level. Her initial count was 19% with sputum eosinophils. AS diagnosis of exclusion DRESS syndrome- associated with lamictal was diagnosed, which is quite rare and so therapy was discontinued and switched to alternative anti seizure therapy. Follow up in 2 months showing eosinophils count dropping to 3% with no recurrent symptoms. DISCUSSION: Several mechanisms are implicated as part of the pathogenesis underlying DRESS syndrome:. Most commonly DRESS is classified as a type IV delayed hypersensitivity reaction. Organ involvement in DRESS is due to eosinophil infiltration of the tissue causing damage. Liver is commonest organ affected followed by kidney and then lungs. Lung involvement can present with symptoms of dyspnea, cough, and/or pleuritic pain, pneumonia, interstitial pneumonitis, pulmonary nodules, or even acute respiratory distress syndrome (ARDS) in severe cases he European Registry for Severe Cutaneous Adverse Reactions (RegiSCAR) is an internationally recognized aid for which provides a clear definition and criteria for diagnosing DRESS syndrome. Though there is reasonable controversy exist about the diagnosis. The most important step in treatment of DRESS syndrome is prompt recognition and withdrawal of the offending drug. Systemic corticosteroids are generally considered the mainstay of therapy. immunosuppressive therapy should be used cautiously. CONCLUSIONS: DRESS is rare syndrome but should be included in the differential diagnosis for patients with peripheral eosinophilia and a medication history with a drug known to be a culprit for it. REFERENCE #1: Cho, Y.-T., C.-W. Yang, and C.-Y. Chu, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System. International journal of molecular sciences, 2017. 18(6): p. 1243. REFERENCE #2: Bocquet, H., M. Bagot, and J.C. Roujeau, Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg, 1996. 15(4): p. 250-7. REFERENCE #3: Taweesedt, P.T., et al., Pulmonary Manifestations of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Systematic Review. Biomed Res Int, 2019. 2019: p. 7863815. DISCLOSURES: No relevant relationships by Abhijit Raval, source=Web Response no disclosure on file for Dhruv Raval

Non-invasive brain stimulation and psychiatric symptoms in neurological disorders

Psychiatric disorders are increasingly recognized as resulting from dysfunction in distributed neural circuitry. The ability of noninvasive brain stimulation to selectively target the circuitry underlying psychiatric disorders has made them valuable tools to study and treat a growing list of conditions including treatment resistant depression, obsessive compulsive disorder, and smoking dependence. FDA approved noninvasive devices for clinical treatment in psychiatry include transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and vagus nerve stimulation (VNS). There is also a range of other noninvasive brain stimulation tools at various stages of research that show promise, including transcranial direct current stimulation (tDCS), magnetic seizure therapy (MST), and focused ultrasound (FUS). Since the initial approval of TMS in 2008, a growing number of devices, coils, and dosing strategies have become available that have the potential to reach a broader range of brain regions and accelerate therapeutic response. Research demonstrates that certain forms of TMS, when given simultaneously with cognitive training, may improve selected cognitive functions. Given the high degree of co-morbidity between neurological and psychiatric disorders, these development in noninvasive neuromodulation tools offer alternatives for neurological patients experiencing psychiatric symptoms. The availability to target neuromodulation via neuronavigation may be particularly useful in neurological patients with focal brain lesions. This presentation will review the state of the art of non-invasive neuromodulation tools in psychiatric care and will highlight the latest work with TMS for depression and cognitive function in patients with neurological disorders such as traumatic brain injury, stroke, and neurodegenerative disorders.

Electroclinical Features in MECP2 Duplication Syndrome: Pediatric Case Series.

MECP2 duplication syndrome (MECP2DS) is an x-linked recessive syndrome characterized by infantile hypotonia, severe neurodevelopmental delay, intellectual disability, progressive spasticity, recurrent infections, and seizures. More than 50% of cases have been associated with epilepsy. Seizure semiology and electroencephalogram (EEG) findings in these patients are poorly described. In this case series, the authors describe the electroclinical features of children with MECP2DS presenting to their institution. In addition, they reviewed seizure types and therapies used. Eight out of 9 patients with MECP2DS developed epilepsy, with 56% having normal initial EEG. Generalized slowing with generalized and focal/multifocal discharges was the most common EEG pattern which is consistent with prior studies. Atonic seizure was the most common semiology. Majority were pharmacoresistant (63%). The goal of this case series is to better define the clinical and electrophysiological aspects of the epilepsy associated with MECP2 duplication syndrome and provide practical guidance regarding management.

Perampanel in the additional therapy of focal and primary generalized tonic-clonic seizures in children 4–12 years old: clinical data, experience of use and practical recommendations

On March 18, 2021, an online council of experts in the field of epilepsy treatment was held, dedicated to the use of perampanel in the additional therapy of focal seizures (FS) and primary generalized tonic-clonic seizures (PGTCS) in children 4–12 years old. During the event, the features of the use of perampanel in this group of patients were discussed, considering the specifics of everyday clinical practice, current possibilities of PGTCS and FS therapy in children, its goals, as well as unsolved problems in the treatment of pediatric patients with PGTCS and FS. Particular attention was paid to the role of perampanel in the treatment of PGTCS and FS in children and its effectiveness in specific types of focal seizures.

Perampanel dosage in plasma samples: development and validation of a novel HPLC method with combined UV-Fluorescence detection

Therapeutic drug monitoring (TDM) is a recognized method to improve the quality of use of antiepileptic drugs, such as perampanel (PRP). It is the first compound in the class of selective non-competitive antagonists of AMPA receptors approved in 2012 in Europe and United States for adjunctive therapy of partial seizures. Although several studies have recently underlined that a general reference range for PRP plasmatic concentration might be difficult to propose, TDM of this drug is important in specific clinical situations, as hepatic or renal impairment or co-administration with enzyme-inducing antiepileptics. Several methods have been described in literature for the determination of PRP in different biological matrices, which include the use of liquid chromatography methods coupled with ultraviolet, fluorescence, mass or tandem-mass spectrometry detection. Here we describe the development and validation of a novel method for the measurement of PRP in plasma samples, based on a HPLC-UV/FL double detection approach and using ketoprofen as internal standard. PRP concentration in a small subset of plasma samples of treated patients was evaluated using both our approach and a commercially available CE-IVD LC–MS/MS method. The results obtained were compared, and confirmed the possibility to use our method as an alternative to LC–MS/MS in clinical routine.

Magnetic seizure therapy for treatment-resistant depression.

Magnetic seizure therapy (MST) is a potential alternative to electroconvulsive therapy (ECT). Reports to date on use of MST for patients with treatment-resistant depression (TRD) are limited. To evaluate the effects of MST in comparison with sham-MST, antidepressant, and other forms of electric or magnetic treatment for adults with TRD. In March 2020, we searched a wide range of international electronic sources for published, unpublished, and ongoing studies. We handsearched the reference lists of all included studies and relevant systematic reviews and conference proceedings of the Annual Meeting of the American College of Neuropsychopharmacology (ACNP), the Annual Scientific Convention and Meeting, and the Annual Meeting of the European College of Neuropsychopharmacology (ECNP) to identify additional studies. All randomised clinical trials (RCTs) focused on MST for adults with TRD. Two review authors extracted data independently. For binary outcomes, we calculated risk ratios (RRs) and 95% confidence intervals (CIs). For continuous data, we estimated mean differences (MDs) between groups and 95% CIs. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using the GRADE approach. Our main outcomes of interest were symptom severity, cognitive function, suicide, quality of life, social functioning, dropout for any reason, serious adverse events, and adverse events that led to discontinuation of treatment. We included three studies (65 participants) comparing MST with ECT. Two studies reported depressive symptoms with the Hamilton Rating Scale for Depression (HAMD). However, in one study, the data were skewed and there was an imbalance in baseline characteristics. Analysis of these two studies showed no clear differences in depressive symptoms between treatment groups (MD 0.71, 95% CI -2.23 to 3.65; 2 studies, 40 participants; very low-certainty evidence). Two studies investigated multiple domains of cognitive function. However most of the outcomes were not measured by validated neuropsychological tests, and many of the data suffered from unbalanced baseline and skewed distribution. Analysis of immediate memory performance measured by the Wechsler Memory Scale showed no clear differences between treatment groups (MD 0.40, 95% CI -4.16 to 4.96; 1 study, 20 participants; very low-certainty evidence). Analysis of delayed memory performance measured by the Wechsler Memory Scale also showed no clear differences between treatment groups (MD 2.57, 95% CI -2.39 to 7.53; 1 study, 20 participants; very low-certainty evidence). Only one study reported quality of life, but the data were skewed and baseline data were unbalanced across groups. Analysis of quality of life showed no clear differences between treatment groups (MD 14.86, 95% CI -42.26 to 71.98; 1 study, 20 participants; very low-certainty evidence). Only one study reported dropout and adverse events that led to discontinuation of treatment. Analysis of reported data showed no clear differences between treatment groups for this outcome (RR 1.38, 95% CI 0.28 to 6.91; 1 study, 25 participants; very low-certainty evidence). Adverse events occurred in only two participants who received ECT (worsening of preexisting coronary heart disease and a cognitive adverse effect). None of the included studies reported outcomes on suicide and social functioning. No RCTs comparing MST with other treatments were identified. Evidence regarding effects of MST on patients with TRD is currently insufficient. Our analyses of available data did not reveal clearly different effects between MST and ECT. We are uncertain about these findings because of risk of bias and imprecision of estimates. Large, long, well-designed, and well-reported trials are needed to further examine the effects of MST.

Epileptic Phenotype and Cannabidiol Efficacy in a Williams–Beuren Syndrome Patient With Atypical Deletion: A Case Report

Epilepsy is a rare clinical manifestation in Williams–Beuren syndrome patients. However, some studies report the presence of infantile spasms and epilepsy in patients carrying larger deletions. Herein, we describe a 13-year-old female affected by Williams–Beuren syndrome and pharmacoresistant epilepsy reporting a de novo large heterozygous 7q11.21q21 deletion (19.4 Mb) also including the YWHAG gene. Studies indicate that cannabidiol is effective as adjunctive therapy for seizures associated with tuberous sclerosis complex, and it is under investigation also in focal cortical dysplasia. When treated with cannabidiol, our patient showed a significant reduction in seizure frequency and intensity, and improved motor and social skills. We hypothesized that CBD could exert a gene/disease-specific effect.

Is Magnetic Seizure Therapy Ready to Round the Corner?

Is Magnetic Seizure Therapy Ready to Round the Corner?

Clinical and Electroencephalography Assessment of the Effects of Brivaracetam in the Treatment of Drug-Resistant Focal Epilepsy.

Introduction: Our aim was to evaluate the clinical and electroencephalographic effects of brivaracetam (BRV) in patients with drug-resistant focal epilepsy. BRV is a new antiepileptic drug (AED) with a high affinity for vesicle protein 2A (SV2A) and recently approved as adjunctive therapy for focal onset seizures. Methods: In this observational study of six-month duration, BRV (50-200 mg) was administered to 76 patients with drug-resistant focal epilepsy, who were ≥16-year-old and who suffered from daily, weekly, monthly and yearly recurrent seizures. At baseline and after six months of follow-up, we performed a neurological visit, neuropsychological tests: Quality of life in epilepsy-31 (QOLIE31), Epworth Sleepiness Scale (ESS), Intrapersonal Emotional Quotient (IEQ) and an electroencephalogram (EEG; inspective and quantitative analysis). Twenty-four patients underwent an overnight switch from levetiracetam (LEV) to BRV. Results: Seizure frequency of the 54 patients remaining at six months was reduced >50% in 29.6% of cases (responders), <50% in 31.5% (non-responders 1), while it remained unchanged in 38.8% (non-responders 2). Twenty-nine percent of patients early discontinued BRV because of lack of efficacy or minor adverse effects (AEs) like irritability, asthenia or headache. Neuropsychological tests in 28 patients demonstrated a significant improvement in I-EPI scores (p=0.04). Comparable results have been found in the subgroup of patients who switched from LEV to BRV. The EEG quantitative analysis showed a significant reduction of alpha absolute power at six months (p=0.03). Theta band power resulted significantly superior in non-responders than in responders (p=0.03). Furthermore, the δ+θ/α+β index resulted more elevated in patients with AEs than in patients without. Conclusions: BRV showed discrete results in terms of efficacy, safety and tolerability, with a good behavioural profile. BRV reduces the power of the alpha band, in correlation with its sedative effects but not with its minor efficacy. Furthermore, the increase in theta band power can be considered as a predictor of scarce response to treatment, while an increase in the δ+θ/α+β index could be a possible predictor of AEs occurrence.

Hyperglycemia With Use of Vagal Nerve Stimulator

Abstract Introduction: In patient with diabetes and refractory epilepsy requiring vagal nerve stimulator (VNS), glycemic management can be challenging. Clinical experience is limited in this scenario. Case Report: A 67-year-old male, BMI 30 kg/m2, with history of type 2 diabetes and hemispheric hemangioma complicated by seizure disorder is referred to our diabetes clinic for evaluation of persistent hyperglycemia. The patient reports 25-year history of seizures that have been difficult to control with antiepileptic drugs alone and eventually requiring VNS placement. Patient has normal kidney (eGFR &amp;gt; 60mL/min) and liver function. His antiepileptic drug regimen consisted of gabapentin and as needed lorazepam. He was never on glucocorticoids. Glycated hemoglobin (HgA1c) at our initial evaluation was 10.1%. His anti-glycemic regimen consisted of glipizide monotherapy. Fasting and pre-prandial blood glucose were in the 200-400mg/dL range with occasional values higher than 500mg/dL. This was confirmed with 14-day continuous glucose monitoring that showed average blood glucose of 287mg/dL with 100 percent above target (higher than 180 mg/dL). We optimized therapy by adding once daily glargine, pioglitazone and continued glipizide. At follow up visit, HgA1c still remained high at 10.5%, despite medication adherence. Patient emphasized that hyperglycemia was related to VNS use and given documented hyperglycemia with blood glucose range 500–600 mg/dL when on higher output current of 2 milliamps, his neurologist approved a trial off VNS for 4 weeks. His glucose improved to average less than 200 mg/dL and HgA1c decreased to 9.1% on the same anti-glycemic regimen. Device was re-started due to recurrence of seizures, however the output current and “on time” were reduced to minimal effective range for optimizing seizure therapy while avoiding hyperglycemia. Subsequent HgA1C improved to 8.7%. Discussion: VNS is a FDA approved device for epilepsy and depression. It works by intermittent stimulation or “on/off” periods. In animal studies, elevation of blood glucose was noted with afferent stimulation. Conversely, efferent activation lowers blood glucose. There are limited human studies on the effects of vagal nerve stimulation on glycemic control. The few available, showed variation in blood glucose based on output current and length of on/off period. This should be factored in during glycemic evaluation and management and close collaboration with neurology is essential. Reference: (1) Strauss H, et al. Cervical Vagal Nerve Stimulation Impairs Glucose Tolerance and Suppresses Insulin Release in Conscious Rats. Physiological Reports 2018; 6(24): 1–9 (2) Strauss H, et al. Effect of Vagus Nerve Stimulation on Blood Glucose Concentration in Epilepsy Patients - Importance of Stimulation Parameters. Physiological Reports 2019; 7(14): 1–10

Comparison of Prolactin and Cortisol Response to Magnetic Seizure Therapy and Electroconvulsive Therapy

Electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) induce therapeutic seizures by delivering current to the brain via scalp electrodes or high-intensity magnetic stimulation, respectively. The induced electric field and the subsequent seizure differ between ECT and MST. We measured peri-treatment serum prolactin and cortisol levels as indicators of the degree of seizure spread induced by the two modalities.