Lower Seizure Threshold Research Articles

Corticohippocampal circuit dysfunction in a mouse model of Dravet syndrome.

Dravet syndrome (DS) is a neurodevelopmental disorder due to pathogenic variants in SCN1A encoding the Nav1.1 sodium channel subunit, characterized by treatment-resistant epilepsy, temperature-sensitive seizures, developmental delay/intellectual disability with features of autism spectrum disorder, and increased risk of sudden death. Convergent data suggest hippocampal dentate gyrus (DG) pathology in DS (Scn1a+/-) mice. We performed two-photon calcium imaging in brain slice to uncover a profound dysfunction of filtering of perforant path input by DG in young adult Scn1a+/- mice. This was not due to dysfunction of DG parvalbumin inhibitory interneurons (PV-INs), which were only mildly impaired at this timepoint; however, we identified enhanced excitatory input to granule cells, suggesting that circuit dysfunction is due to excessive excitation rather than impaired inhibition. We confirmed that both optogenetic stimulation of entorhinal cortex and selective chemogenetic inhibition of DG PV-INs lowered seizure threshold in vivo in young adult Scn1a+/- mice. Optogenetic activation of PV-INs, on the other hand, normalized evoked responses in granule cells in vitro. These results establish the corticohippocampal circuit as a key locus of pathology in Scn1a+/- mice and suggest that PV-INs retain powerful inhibitory function and may be harnessed as a potential therapeutic approach toward seizure modulation.

Partial protective effects of cannabidiol against PTZ-induced acute seizures in female rats during the proestrus–estrus transition

Approximately 70% of women with epilepsy experience additional challenges in seizure exacerbation due to hormonal changes, particularly during fluctuations of estrogen–progesterone levels in the menstrual cycle, which is known as catamenial epilepsy. In animal models of epilepsy, a sustained increase in seizure frequency has been observed in female rats during the proestrus–estrus transition when estrogen levels are high and progesterone levels are low resembling catamenial epilepsy. Cannabidiol (CBD) has been proposed to have anticonvulsant and anti-inflammatory effects, able to decrease seizure duration and increase seizure threshold in rats with epilepsy. However, most studies have used males to investigate the pharmacological effects of CBD on seizures, and the neuroprotective effects of CBD against seizures exacerbated by hormonal fluctuations in females are still little explored. Given this scenario, the aim of the present study was to investigate whether CBD would protect against acute seizures induced by pentylenetetrazole (PTZ) in female rats during a pro-convulsant hormonal phase. Therefore, CBD (50 mg/kg) or saline was administered during the proestrus–estrus transition phase, 1 h prior to induction of seizures with PTZ (60 mg/kg), and the following parameters were recorded: duration, latency to first seizure, as well as percentage of convulsing animals (incidence), mortality, and severity of seizures. Brains were processed for immunohistochemistry for microglial cells (Iba-1), and blood was collected for the analysis of cytokines (IL-1β, IL-6, IL-10, and TNF-α). Cannabidiol pre-treated rats showed a significant reduction in duration and severity of seizures, and IL-1β levels, although the latency, incidence of seizures, and mortality rate remained unchanged as well the quantification of microglia in the selected areas. Therefore, acute administration of CBD in a single dose prior to seizure induction showed a partial neuroprotective effect against seizure severity and inflammation, suggesting that female rats in the proconvulsant phase of proestrus–estrus have a low seizure threshold and are more resistant to the anticonvulsant effects of CBD. It appears that other doses or administration windows of CBD may be required to achieve a full protective effect against seizures, suggesting that CBD could be used as an adjunctive therapy during fluctuations of estrogen–progesterone levels. In this sense, considering the hormonal fluctuation as a seizure-potentiating factor, our study contributes to understand the anticonvulsant activity of CBD in females in a pro-convulsant hormonal phase, similar to catamenial seizures in humans.

Clinical profile of seizure disorder in hospitalized patients in tertiary care center - A prospective cross-sectional study

Background: Knowledge regarding people affected with epilepsy is essential for accurate planning and management of patients. This study was conducted to study clinical profile of seizure disorder in the patients hospitalized in a tertiary care hospital of Tamil Nadu. Aims and Objectives: To study clinical profile of seizure disorder in patients hospitalized in Coimbatore government medical college hospital. Materials and Methods: This study was a single center hospital based cross-sectional study of the clinical profile of seizure disorder in hospitalized patients at tertiary care center of Tamil Nadu, Neurology department the 2 years from 2018 to 2020. All the patients presenting with complaints of seizures were included in this study. Results: This study included a total of 321 patients with epilepsy. Their ages ranged between 10 and 100 years. 180 of the study population were males and 141 were female patients. 30% of patients had new onset seizures. Fever precipitated seizure in 16% of the subjects. Excitation, sleep deprivation, fever, watching television, and head trauma showed a strong association with generalized epilepsy. The majority of the patients had generalized tonic-clonic seizure, followed by focal neurological deficit. 98% of patients responded to treatment and they did not had recurrent episodes of seizure. Conclusion: The sample size of our cohorts is relatively small. It is possible that some prognosis factors may be missed due to the small sample size. Further studies with a larger sample cohort are required. Uneducated and low socioeconomic make people vulnerable to seizures because of lack of awareness, poor compliance to medicines, not detection of seizure provoking factor, repeated exposure to seizure provoking factor, prevalence of alcoholism, and thus lowering seizure threshold. There is a treatment gap still because of epilepsy and appropriate usage of resources will help to reduce this treatment gap and decreases epilepsy associated morbidity and mortality.

Scorpion Envenomation of Lactating Rats Decreases the Seizure Threshold in Offspring.

Few data are available in the literature describing the long-term effects of envenoming in the perinatal period. In this study, the relationship between envenoming of lactating rats and possible behavioral changes in the mother and in her offspring were investigated. Lactating Wistar rats received a single dose of T. serrulatus crude venom on postnatal days 2 (V2), 10 (V10) or 16 (V16), and had their maternal behavior evaluated. The seizure threshold was evaluated in adulthood offspring. A decrease in maternal care during envenoming was observed in V2 and V10 groups. The retrieval behavior was absent in the V2 group, and a lower seizure threshold in the adult offspring of all groups was observed. During envenoming, mothers stayed away from their offspring for a relatively long time. Maternal deprivation during the early postnatal period is one of the most potent stressors for pups and could be responsible, at least in part, for the decrease in the convulsive threshold of the offspring since stress is pointed to as a risk factor for epileptogenesis. Furthermore, the scorpionic accident generates an intense immune response, and inflammation in neonates increases the susceptibility to seizures in adulthood. Therefore, maternal envenoming during lactation can have adverse effects on offspring in adulthood.

In vitro and in vivo anti-epileptic efficacy of eslicarbazepine acetate in a mouse model of KCNQ2-related self-limited epilepsy.

The KCNQ2 gene encodes for the Kv 7.2 subunit of non-inactivating potassium channels. KCNQ2-related diseases range from autosomal dominant neonatal self-limited epilepsy, often caused by KCNQ2 haploinsufficiency, to severe encephalopathies caused by KCNQ2 missense variants. In vivo and in vitro effects of the sodium channel blocker eslicarbazepine acetate (ESL) and eslicarbazepine metabolite (S-Lic) in a mouse model of self-limited neonatal epilepsy as a first attempt to assess the utility of ESL in the KCNQ2 disease spectrum was investigated. Effects of S-Lic on in vitro physiological and pathological hippocampal neuronal activity in slices from mice carrying a heterozygous deletion of Kcnq2 (Kcnq2+/- ) and Kcnq2+/+ mice were investigated. ESL in vivo efficacy was investigated in the 6-Hz psychomotor seizure model in both Kcnq2+/- and Kcnq2+/+ mice. S-Lic increased the amplitude and decreased the incidence of physiological sharp wave-ripples in a concentration-dependent manner and slightly decreased gamma oscillations frequency. 4-Aminopyridine-evoked seizure-like events were blocked at high S-Lic concentrations and substantially reduced in incidence at lower concentrations. These results were not different in Kcnq2+/+ and Kcnq2+/- mice, although the EC50 estimation implicated higher efficacy in Kcnq2+/- animals. In vivo, Kcnq2+/- mice had a lower seizure threshold than Kcnq2+/+ mice. In both genotypes, ESL dose-dependently displayed protection against seizures. S-Lic slightly modulates hippocampal oscillations and blocks epileptic activity in vitro and in vivo. Our results suggest that the increased excitability in Kcnq2+/- mice is effectively targeted by S-Lic high concentrations, presumably by blocking diverse sodium channel subtypes.

Hyperexcitability and brain morphological differences in mice lacking the cystine/glutamate antiporter, system xc.

System xc- (Sxc- ) is a heteromeric antiporter (L-cystine/L-glutamate exchanger) expressed predominately on astrocytes in the central nervous system. Its activity contributes importantly to the maintenance of the ambient extracellular glutamate levels, as well as, to cellular redox homeostasis. Since alterations in glutamate levels and redox modifications could cause structural changes, we analyzed gross regional morphology of thionin-stained brain sections and cellular and subcellular morphology of Golgi-Cox stained layer V pyramidal neurons in the primary motor cortex (PM1) of mice naturally null for SLC7A11 (SLC7A11sut/sut )-the gene that encodes the substrate specific light chain (xCT) for Sxc- . Intriguingly, in comparison to age- and sex-matched wild-type (SLC7A11+/+ ) littermate controls, we found morphologic changes-including increased dendritic complexity and mushroom spine area in males and reduced corpus callosum and soma size in females-that have previously been described, in each case, as morphological correlates of excitability. Consistent with this, we found that both male and female SLC7A11sut/sut mice had lower convulsive seizure thresholds and greater seizure severity than their sex-matched wild-type (SLC7A11+/+ ) littermates after acute challenge with two pharmacologically distinct chemoconvulsants: the Glu receptor agonist, kainic acid (KA), or the GABAA receptor antagonist, pentylenetetrazole (PTZ). These results suggest that the loss of Sxc- signaling in males and females perturbs excitatory/inhibitory (E/I) balance in vivo, potentially through its regulation of cellular and subcellular morphology.

ATP and adenosine-Two players in the control of seizures and epilepsy development.

Despite continuous advances in understanding the underlying pathogenesis of hyperexcitable networks and lowered seizure thresholds, the treatment of epilepsy remains a clinical challenge. Over one third of patients remain resistant to current pharmacological interventions. Moreover, even when effective in suppressing seizures, current medications are merely symptomatic without significantly altering the course of the disease. Much effort is therefore invested in identifying new treatments with novel mechanisms of action, effective in drug-refractory epilepsy patients, and with the potential to modify disease progression. Compelling evidence has demonstrated that the purines, ATP and adenosine, are key mediators of the epileptogenic process. Extracellular ATP concentrations increase dramatically under pathological conditions, where it functions as a ligand at a host of purinergic receptors. ATP, however, also forms a substrate pool for the production of adenosine, via the action of an array of extracellular ATP degrading enzymes. ATP and adenosine have assumed largely opposite roles in coupling neuronal excitability to energy homeostasis in the brain. This review integrates and critically discusses novel findings regarding how ATP and adenosine control seizures and the development of epilepsy. This includes purine receptor P1 and P2-dependent mechanisms, release and reuptake mechanisms, extracellular and intracellular purine metabolism, and emerging receptor-independent effects of purines. Finally, possible purine-based therapeutic strategies for seizure suppression and disease modification are discussed.

PRG5 Knockout Precipitates Late-Onset Hypersusceptibility to Pilocarpine-Induced Juvenile Seizures by Exacerbating Hippocampal Zinc Signaling-Mediated Mitochondrial Damage

IntroductionEpileptogenesis is understood as the plastic process that produces a persistent reorganization of the brain’s neural network after a precipitating injury (recurrent neonatal seizures, for instance) with a latent period, finally leading to neuronal hyperexcitability. Plasticity-related genes (PRGs), also known as lipid phosphate phosphatase-related proteins (PLPPRs), are regulators of mitochondrial membrane integrity and energy metabolism. This study was undertaken to determine whether PRG5 gene knockout contributes to the delayed hypersensitivity induced by developmental seizures and the aberrant sprouting of hippocampal mossy fibers, and to determine whether it is achieved through the mitochondrial pathway. Here, we developed a “twist” seizure model by coupling pilocarpine-induced juvenile seizures with later exposure to penicillin to test the long-term effects of PRG5 knockout on seizure latency through comparison with wild-type (WT) mice. Hippocampal mossy fiber sprouting (MFS) was detected by Timm staining. In order to clarify the mechanism of the adverse reactions triggered by PRG5 knockout, hippocampal HT22 neuronal cultures were exposed to glutamate, with or without PRG5 interference. Mitochondrial function, oxidative stress indicators and zinc ion content were detected.ResultsPRG5 gene knockout significantly reduced the seizure latency, and aggravated the lowered seizure threshold induced by developmental seizures. Besides, knockout of the PRG5 gene reduced the MFS scores to a certain extent. Furthermore, PRG5 gene silencing significantly increases the zinc ion content in hippocampal neurons, impairs neuronal activity and mitochondrial function, and exacerbates glutamate-induced oxidative stress damage.ConclusionIn summary, PRG5 KO is associated with significantly greater hypersusceptibility to juvenile seizures in PRG5(–/–) mice compared with WT mice. These effects may be related to the hippocampal zinc signaling. The effects do not appear to be related to changes in MFS because KO mice with juvenile seizures had the shortest seizure latencies but exhibited less MFS than WT mice with juvenile seizures.

Hypoxic-Ischemic Encephalopathy-Induced Seizure in an 11-Year-Old Female

Hypoxic-ischemic encephalopathy (HIE) typically manifests in the neonatal period. The degree of hypoxia following intrapartum asphyxia determines the structural changes in the brain, which can cause functional deficits in the affected child leading to developmental deficits and recurrent seizures. Management requires physical therapy, occupational therapy, and anti-seizure medications. We present a rare case of an 11-year-old female with a past medical history of epilepsy and cerebral atrophy secondary to hypoxic injury at birth. The patient presented to the hospital following a witnessed seizure and loss of consciousness for one hour. Given the past medical history and clinical findings, it was determined that a mild-to-moderate encephalopathic process resulted in a lower seizure threshold. HIE can manifest beyond the neonate years mainly due to the structural changes within the brain. Therefore, it is essential to understand aspects of HIE beyond the neonate years to manage this condition for a better patient outcome.

Neonatal Brain Injury From SARS-CoV-2: Fact or Fiction?

Neonatal Brain Injury From SARS-CoV-2: Fact or Fiction?

A Novel GATA3 Variant Causing Familial Hypoparathyroidism, Renal Agenesis and Sensorineural Deafness Presenting With Atypical Symptoms of Chronic Hypocalcaemia

Introduction: Familial hypoparathyroidism is a rare cause of hypocalcaemia. We report a case of long-standing hypocalcaemia secondary to hypoparathyroidism caused by a novel GATA3 variant resulting in multiple organ involvement. Case: A 20 year old girl was referred to our bone metabolic clinic for hypocalcaemia. Her past medical history included Bechet’s disease, epilepsy and depression. She had bilateral sensorineural hearing loss and encephalitis as a child. She underwent right nephrectomy for an atrophic non-functioning kidney at the age of 16. Current medication included hydroxychloroquine, diazepam, oral calcium and cholecalciferol. It was noted that the hypocalcaemia dated back to 8 years, she denied any typical symptoms of hypocalcaemia but she did report visual and auditory hallucinations, fatigue and had low seizure threshold. She sustained recurrent fractures of her arm, elbow and wrist. Initial investigations: Corrected calcium 1.88 (2.20-2.60mmol/L), Phosphate 1.54 (0.80–1.50mmol/L), PTH 1.2 (1.6–6.9pmol/), 25-OH vitamin D 37 (50-120nmol/L). Myeloma screen, thyroid, renal and liver functions were all within the normal reference range. Other bone markers: Serum Procollagen Type 1 Amino Terminal Peptide was mildly raised at 82 (19-69ug/L), CTX 0.42 (0.1-0.5ug/L), 1,25 OH Vitamin D 29 (55-139pmol/L), 24,25-dihydroxyvitamin D was normal with normal 25:24,25 Dihyroxyvitamin D ratio at 18 normal. Bone density was in the normal range for her age. MRI of the brain was normal with no evidence of calcification. There was a family history of hypocalcemia in her estranged father. Subsequent genetic analysis showed a novel likely pathogenic GATA3 missense variant (c.961T>C p.(Cys321Arg). She was started on alfacalcidol and achieved near normocalcemia with adjusted calcium levels of 2.18nmol/L. Conclusion: Pathogenic variants in the GATA3 gene are responsible for Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome. In our patient, a novel missense variant in GATA3, p.(Cys321Arg), has been detected. This variant disrupts one of four conserved cysteine residues within a zinc-finger domain, which is involved in DNA binding and is presumed to have a deleterious effect on protein function. Patients may have longstanding asymptomatic hypocalcaemia with atypical features hence genetic testing is recommended in patient with multi-organ involvement. Alfacalcidol successfully restored calcium homeostasis in this case.

Association of Iron Deficiency Anemia with Febrile Seizure in Children in a Tertiary Care Hospital.

Febrile seizure is the most common cause of seizure in children. Iron deficiency, by lowering seizure threshold, is proposed to be one of the risk factors for febrile seizure. Many studies have been done to determine the association of iron deficiency anemia with febrile seizure but the results are controversial. Hence, the present study was conducted to evaluate the association of iron deficiency anemia with febrile seizure in Nepalese children. A prospective age and sex matched case control study was performed in 68 cases of febrile seizures and 68 controls of febrile illness without seizure after calculating the sample size. The study was conducted from October 21, 2019 to October 20, 2020 in Pediatric ward and intensive care unit of College of Medical Sciences, Bharatpur, Nepal after obtaining ethical clearance from institutional review committee. Data entry was done in statistical packages for the social science version 20. Mean of haematological parameters (haemoglobin and mean corpuscular volume) as well as mean of serum iron, ferritin and transferrin saturation were significantly less and total iron binding capacity was significantly high in cases as compared to controls (P <0.05). Iron deficiency anemia was significantly associated with cases (59.7%), with odds ratio of 2.5 (95% confidence interval =1.24 - 5.01) as compared to control (40.3%) (P <0.05). Iron deficiency anemia may be considered one of the risk factors for febrile seizure in children. Hence, Children with febrile seizure should be investigated and treated for Iron deficiency anemia.

Increased Excitatory Synaptic Transmission Associated with Adult Seizure Vulnerability Induced by Early-Life Inflammation in Mice.

Early-life inflammatory stress increases seizure susceptibility later in life. However, possible sex- and age-specific differences and the associated mechanisms are largely unknown. C57BL/6 mice were bred in house, and female and male pups were injected with lipopolysaccharide (LPS; 100 μg/kg, i.p.) or vehicle control (saline solution) at postnatal day 14 (P14). Seizure threshold was assessed in response to pentylenetetrazol (1% solution, i.v.) in adolescence (∼P40) and adulthood (∼P60). We found that adult, but not adolescent, mice treated with LPS displayed ∼34% lower seizure threshold compared with controls. Females and males showed similar increased seizure susceptibility, suggesting that altered brain excitability was age dependent, but not sex dependent. Whole-cell recordings revealed no differences in excitatory synaptic activity onto CA1 pyramidal neurons from control or neonatally inflamed adolescent mice of either sex. However, adult mice of both sexes previously exposed to LPS displayed spontaneous EPSC frequency approximately twice that of controls, but amplitude was unchanged. Although these changes were not associated with alterations in dendritic spines or in the NMDA/AMPA receptor ratio, they were linked to an increased glutamate release probability from Schaffer collateral, but not temporoammonic pathway. This glutamate increase was associated with reduced activity of presynaptic GABAB receptors and was independent of the endocannabinoid-mediated suppression of excitation. Our new findings demonstrate that early-life inflammation leads to long-term increased hippocampal excitability in adult female and male mice associated with changes in glutamatergic synaptic transmission. These alterations may contribute to enhanced vulnerability of the brain to subsequent pathologic challenges such as epileptic seizures.SIGNIFICANCE STATEMENT Adult physiology has been shown to be affected by early-life inflammation. Our data reveal that early-life inflammation increases excitatory synaptic transmission onto hippocampal CA1 pyramidal neurons in an age-dependent manner through disrupted presynaptic GABAB receptor activity on Schaffer collaterals. This hyperexcitability was seen only in adult, and not in adolescent, animals of either sex. The data suggest a maturation process, independent of sex, in the priming action of early-life inflammation and highlight the importance of studying mature brains to reveal cellular changes associated with early-life interventions.

New therapeutic agents marketed in 2020: Part 1

New therapeutic agents marketed in 2020: Part 1

Psychiatric Aspects of Epilepsy

A seizure is defined as transient change in neurological functioning which is characterised by hypersynchronous discharges of neurons in the brain regions whereas epilepsy is defined as a syndrome consisting of various recurrent seizures and it is associated with the psychological and neuropathological effects. Early recognition and management of psychiatric disorders in patients with epilepsy is extremely important, because it improves the quality of life and aids in better seizure control. Newer antiepileptics with less interaction with psychotropics and less behavioural manifestations should be used for management of epilepsy; and psychotropics having low potential for lowering seizure threshold are generally preferred. A holistic approach to assess psychiatric comorbidity and judicious use of medicine can help in comprehensive patient care planning and reduced health burden.

A Review on Pathophysiology and Prognosis of Seizures in Covid-19

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel infectious disease. It has caused one of the most destructive pandemics in human history with symptoms ranging from mild to severe. In severe cases, patients can develop pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. Among the neurological manifestations, seizures have been most commonly reported. Different mechanisms have been proposed for the occurrence of seizures in COVID-19 patients. Hypoxia and severe metabolic and electrolyte derangements may theoretically lower seizure thresholds. Furthermore, cytokine storm and the involvement of ACE receptors are also being considered as possible etiologies for these seizures. We performed a detailed literature review and included 15 case reports of seizures in COVID patients. The majority of the patients had past conditions ranging from diabetes and hypertension to as severe as fahr syndrome, AF (Atrial Fibrillation), and MM (Multiple Myeloma). Most of the patients with fits had moderate to severe COVID-19. Most patients were treated with levetiracetam, a very effective anti-epileptic. For COVID-19 patients with seizures, a multidisciplinary approach should be considered to enhance the care of the patients. It is very important to do a long-term follow-up of these patients to fully understand if these patients tend to develop epilepsy.

Drug Treatment of Epilepsy Neuropsychiatric Comorbidities in Children.

There is increasing recognition that epilepsy can be associated with a broad spectrum of comorbidities. While epileptic seizures are an essential element of epilepsy in children, there is a spectrum of neurological, mental health and cognitive disorders that add to the disease burden of childhood epilepsy resulting in a decreased quality of life. The most common comorbid conditions in childhood epilepsy include depression, anxiety, autism spectrum disorders, sleep disorders, attention deficits, cognitive impairment, and migraine. While epilepsy can result in comorbidities, many of the comorbidities of childhood have a bi-directional association, with the comorbid condition increasing risk for epilepsy and epilepsy increasing the risk for the comorbid condition. The bidirectional feature of epilepsy and the comorbidities suggest a common underlying pathological basis for both the seizures and comorbid condition. While recognition of the comorbid conditions of pediatric epilepsies is increasing, there has been a lag in the development of effective therapies partly out of concern that drugs used to treat the comorbid conditions could increase seizure susceptibility. There is now some evidence that most drugs used for comorbid conditions are safe and do not lower seizure threshold. Unfortunately, the evidence showing drugs are effective in treating many of the childhood comorbidities of epilepsy is quite limited. There is a great need for randomized, placebo-controlled drug trials for efficacy and safety in the treatment of comorbidities of childhood epilepsy.

Seizure threshold manipulation in electroconvulsive therapy via repetitive transcranial magnetic stimulation. A novel way of augmentation?

IntroductionA high seizure threshold (ST) is an impeding factor in certain patients, potentially preventing a successful electroconvulsive therapy (ECT) treatment. Several pharmacological and non-pharmacological methods have been put forward to augment ECT in such patients, however, to this date, only a handful of case reports existed about the potential role of repetitive transcranial magnetic stimulation (rTMS), as an augmentation method. Objectivesand Methods: In this randomized, double-blinded, sham controlled study, we set out to test the hypothesis of whether the application of high frequency transcranial magnetic stimulation (HF rTMS) lowers the seizure threshold for electroconvulsive therapy and whether it has an effect on other aspects of ECT treatment, such as seizure duration (SD), efficacy and safety. Results46 patients treated for a major depressive episode, indicated for ECT, were recruited to this study. A significantly lower seizure threshold was observed in the experimental group during ECT titration, on average a decrease by 34.55%, from 34.23 mC to 22.4 mC, p < 0.001 (Wilcox test). We had not observed a significant effect of TMS stimulation before ECT on seizure duration or clinical outcome. Another potentially important observation of this study is that 4 patients in the experimental group developed transient symptoms of hypomania/mania, all of which were stabilized after the combined stimulation protocol was halted spontaneously within a week, without the need to administer mood stabilizers. ConclusionIt is likely that HF rTMS stimulation prior to ECT is a novel and simple way of reducing the ST, which is useful in certain groups of patients undergoing this important treatment modality.

Seizures and Epilepsy in Times of Corona Virus Disease 2019 Pandemic.

The end of the year 2019 was marked by novel coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) outbreak in China that rapidly spread to the rest of the world. While the involvement of the lower respiratory system causing pneumonia is identified as the primary target of the virus, extra-pulmonary manifestations, especially of the central nervous system, are also being increasingly reported. Previous research on Middle East respiratory syndrome coronavirus and SARS-CoV have shown neurological involvement in human coronavirus infections. While several cases of seizures have been reported in patients with coronavirus disease 2019 (COVID-19) patients, there is no specific data to suggest an association of COVID-19 with epilepsy. Epilepsy patients on immunosuppressive medications may have a higher risk of contracting the viral infection. There can be an indirect relation of COVID-19 to epilepsy as the viral infection is associated with fever in most COVID-19 cases, which can lower seizure threshold. Additionally, inadequate sleep and stress due to ongoing pandemic of coronavirus can be another trigger for seizure precipitation in epilepsy patients. Drug compliance, availability of antiepileptic drugs, and drug interactions with COVID-19 experimental drugs are major concerns in epilepsy patients. Adopting telemedicine services and the use of epilepsy helplines may be important in assisting epilepsy patients and ensuring that treatment continues uninterrupted.

Cannabinoid receptors and the proconvulsant effect of toxoplasmosis in mice

Toxoplasmosis is an infectious disease caused by the intracellular parasite Toxoplasma gondii that harms the brain and increases the risk of epilepsy acquisition. It is well known that cannabinoid (CB) signaling is activated following brain insults and protects the neurons from excitotoxicity and inflammation. We examined the role of CB neurotransmission in the proconvulsant effect of Toxoplasmosis in mice.Toxoplasmosis was established in mice by intraperitoneal injection of T. gondii cysts. The mice with acute and/or chronic Toxoplasma infection were pretreated (through intracerebroventricular injection) with CB1 and CB2 receptor agonists (ACEA and HU308) and antagonists (AM251 and AM630), as well as JZL184 (the irreversible inhibitor of mono acyl glycerol lipase, enzyme degrading the endogenous cannabinoid 2-Acyl glycerol). The seizure threshold was then measured by tail vein infusion of pentylenetetrazole.In healthy uninfected mice JZL184, ACEA, and AM630 increased the seizure threshold in a dose-dependent manner, whereas AM251 and HU308 showed dose-dependent proconvulsant effect. Mice with acute and/or chronic infection had a substantial lower seizure threshold than the uninfected mice. JZL 184, ACEA and AM630 inhibited proconvulsant effect of Toxoplasmosis, while AM251 and HU308 intensified proconvulsant effect of Toxoplasmosis.CB receptors play a role in proconvulsant effect of Toxoplasmosis in mice.