Venous and arterial cerebral thrombosis: a COVID-19 dual pathology and single possible etiology—a case report

Background Corona virus disease of the year 2019 (COVID-19) is still devastating the world for more than 19 months since its declaration as a pandemic by world health organization. Its manifestations does not stand at respiratory system but involves other body systems including central nervous system and its vasculature. In the following case report, cerebral venous and arterial thrombosis is detected in a case just in convalescence from COVID-19 with still detected positive IgM. Case presentation A 68-year-old female presenting with disturbed conscious level, bilateral convergent squint, single attack of generalized seizures, left sided dense weakness within a short time from catching COVID-19 and while still in quarantine hospital in recovery phase from infection. Magnetic resonance studies revealed bilateral cortical border zone infarcts as well as left lateral dural sinus and deep venous thrombosis. Conclusion Along the forth wave, COVID-19 is still hitting hardly the central nervous system vasculature.

Escalation to Barbiturate-Induced Coma for Refractory Seizures after Liver Transplantation

Seizures after liver transplantation were previously thought to be a reliable harbinger of catastrophe, but more recent studies have found seizure activity to be relatively common, and most cases do not result in a poor outcome. Generalized seizures are the most common, and they typically occur de novo within the first two weeks after transplantation. The underlying cause for seizure activity in these patients may be complex, with potential etiologies including metabolic, infectious, cerebrovascular, and medication-induced causes. Identification of the underlying cause and the use of antiepileptic drugs (AEDs) is crucial for minimizing risk to the patient’s neurologic and overall health. In this report, we present the case of a patient with refractory seizures unresponsive to conventional treatment, requiring prolonged barbiturate burst suppression with ventilator support. Seizure activity eventually ceased, and the patient made a full recovery.

Seizures Caused by Exposure to Hyperbaric Oxygen in Rats Can Be Predicted by Early Changes in Electrodermal Activity

Hyperbaric oxygen (HBO2) is breathed during undersea operations and in hyperbaric medicine. However, breathing HBO2 by divers and patients increases the risk of central nervous system oxygen toxicity (CNS-OT), which ultimately manifests as sympathetic stimulation producing tachycardia and hypertension, hyperventilation, and ultimately generalized seizures and cardiogenic pulmonary edema. In this study, we have tested the hypothesis that changes in electrodermal activity (EDA), a measure of sympathetic nervous system activation, precedes seizures in rats breathing 5 atmospheres absolute (ATA) HBO2. Radio telemetry and a rodent tether apparatus were adapted for use inside a sealed hyperbaric chamber. The tethered rat was free to move inside a ventilated animal chamber that was flushed with air or 100% O2. The animal chamber and hyperbaric chamber (air) were pressurized in parallel at ~1 atmosphere/min. EDA activity was recorded simultaneously with cortical electroencephalogram (EEG) activity, core body temperature, and ambient pressure. We have captured the dynamics of EDA using time-varying spectral analysis of raw EDA (TVSymp), previously developed as a tool for sympathetic tone assessment in humans, adjusted to detect the dynamic changes of EDA in rats that occur prior to onset of CNS-OT seizures. The results show that a significant increase in the amplitude of TVSymp values derived from EDA recordings occurs on average (±SD) 1.9 ± 1.6 min before HBO2-induced seizures. These results, if corroborated in humans, support the use of changes in TVSymp activity as an early “physio-marker” of impending and potentially fatal seizures in divers and patients.

Anticonvulsive Effects and Pharmacokinetic Profile of Cannabidiol (CBD) in the Pentylenetetrazol (PTZ) or N-Methyl-D-Aspartate (NMDA) Models of Seizures in Infantile Rats

In spite of use of cannabidiol (CBD), a non-psychoactive cannabinoid, in pediatric patients with epilepsy, preclinical studies on its effects in immature animals are very limited. In the present study we investigated anti-seizure activity of CBD (10 and 60 mg/kg administered intraperitoneally) in two models of chemically induced seizures in infantile (12-days old) rats. Seizures were induced either with pentylenetetrazol (PTZ) or N-methyl-D-aspartate (NMDA). In parallel, brain and plasma levels of CBD and possible motor adverse effects were assessed in the righting reflex and the bar holding tests. CBD was ineffective against NMDA-induced seizures, but in a dose 60 mg/kg abolished the tonic phase of PTZ-induced generalized seizures. Plasma and brain levels of CBD were determined up to 24 h after administration. Peak CBD levels in the brain (996 ± 128 and 5689 ± 150 ng/g after the 10- and 60-mg/kg doses, respectively) were reached 1–2 h after administration and were still detectable 24 h later (120 ± 12 and 904 ± 63 ng/g, respectively). None of the doses negatively affected motor performance within 1 hour after administration, but CBD in both doses blocked improvement in the bar holding test with repeated exposure to this task. Taken together, anti-seizure activity of CBD in infantile animals is dose and model dependent, and at therapeutic doses CBD does not cause motor impairment. The potential risk of CBD for motor learning seen in repeated motor tests has to be further examined.

SLC7A3: In Silico Prediction of a Potential New Cause of Childhood Epilepsy

We report an in-depth genetic analysis in an 11-year-old boy with drug-resistant, generalized seizures and developmental disability. Three distinct variants of unknown clinical significance (VUS) were detected by whole exome sequencing (WES) but not by initial genetic analyses (microarray and epilepsy gene panel). These variants involve the SLC7A3, CACNA1H, and IGLON5 genes, which were subsequently evaluated by computational analyses using the InterVar tool and MutationTaster. While future functional studies are necessary to prove the pathogenicity of a certain VUS, segregation analyses over three generations and in silico predictions suggest the X-linked gene SLC7A3 (transmembrane solute carrier transporter) as the likely culprit gene in this patient. In addition, a search via GeneMatcher unveiled two additional patients with a VUS in SLC7A3. We propose SLC7A3 as a likely candidate gene for epilepsy and/or developmental/cognitive delay and provide an overview of the 27 SLC genes related to epilepsy by other preclinical and/or clinical studies.

Pediatric COVID-19: Low Incidence, but Possible Fatality—A Case Report and a Review of the Literature

Background: Pediatric COVID-19 is a current health burden mostly due to the lack of knowledge in terms of symptoms, clinical course and management. COVID-19-associated coagulopathy is one of the most recently described complications among adults, along with acquired thrombophilia resulting in an increased risk for venous, arterial and microvascular thrombosis. Case presentation: We report the case of a 4-year-old male child, admitted to our clinic for generalized seizures being intubated and mechanically ventilated before admission, with a personal history of ureterovesical junction obstruction, mild hydronephrosis, and an episode of generalized seizures. The laboratory tests revealed anemia, an increased number of monocytes, and a mildly increased C-reactive protein. A real-time polymerase chain reaction (RT-PCR) of the oropharyngeal swab was performed and it tested positive for SARS-CoV-2 in the child and both of his parents. The thoracic CT showed consolidation in the lower lobe of the left lung associated with an opacity in the right apex, suggesting possible atelectasis. We initiated antibiotic, antiviral, corticosteroids, as well as anticoagulants and antipyretics, continuing the chronic anticonvulsant therapy. The patient’s condition deteriorated progressively, and, after 72 h of hospitalization, he developed desaturation and bradycardia. The laboratory parameters on the third day showed leucopenia, neutropenia, increased creatine kinase, a high ferritin level, hypoalbuminemia, a prolonged prothrombin time and an increased international normalized ration. The patient died on the fourth day of admission. Conclusion: In spite of its low incidence and frequent benign clinical course, COVID-19 complications such as coagulopathy might represent a leading cause of death, even in pediatric patients.

Levetiracetam Induced Hyperkalemia – A Rare Side Effect in Elderly with Pre-Existing Subclinical Renal Insufficiency Presenting with Bradyarrhythmia

Levetiracetam is a commonly used drug in today’s world for long term management of partial as well as generalized seizures mainly due its major advantage that is has so few and non-threatening side effects[1].In the following case scenario, we show how a 70 years old male presented with severe hyperkalemia and after no other common culprits were seen, it was thought to be a side effect therapy with levetiracetam and after discontinuing it and managing hyperkalemia, the patient’s condition improved from a very critical state. We also show a rare form ECG presentation of severe hyperkalemia in the form of bradyarrhythmia with absent P waves. Our experience shows that unpredictable and rare side effects of new anti-epileptic drugs should be given attention and such cases often go undiagnosed.

IL4 Reduces Epileptogenesis Susceptibility Acutely After TBI: The Role of Macrophage/Microglia Polarization

Traumatic brain injury (TBI) is responsible for 5% of all epilepsy cases, which are known as post-traumatic epilepsy. Macrophage/microglia are key players in TBI pathogenesis. They are activated after TBI, transform to inflammatory phenotype (M1) and trigger neuroinflammation, which provokes epileptogenesis. Interleukin-4 (IL-4) is a well-known polarizer of macrophage/microglia to the anti-inflammatory phenotype (M2). We tested the effect of IL-4 on the rate of epileptogenesis, brain expression of inflammatory and anti-inflammatory cytokines, and the lesion size in traumatic rats. Trauma was exerted to temporo-parietal cortex of rats by Controlled Cortical Impact. Thereafter, rats received a single dose (100ng/rat) of IL-4 through intracerebroventricular injection. After 24h, pentylenetetrazole (PTZ) kindling started and development of generalized seizures was recorded. Level of TNF-α, TGF-β, IL-10, and arginase-1 (Arg-1) was measured in the brain by immunoblotting at 6h, 12h, 24h, 48h, and 5 days after TBI. The lesion size and cell survival were determined by staining. Traumatic rats were kindled by 5±1 PTZ injections (significantly less than 11±2 injections of control and sham-operated rats, p<0.001). IL-4 did not change kindling rate in sham-operated rats but inhibited acceleration of kindling rate in traumatic rats (13±1 PTZ injections, p<0.001). IL-4 decreased post-TBI overexpression of TNF-α (6h, p<0.001) whereas upregulated post-TBI expression of TGF-β (48h, p<0.001), IL-10 (24h, p<0.05; 48h, p<0.01), and Arg-1 (24h, p<0.001). IL-4 decreased lesion volume and number of dead neurons. IL-4 suppresses TBI-induced acceleration of epileptogenesis in rats by directing macrophage/microglia to the anti-inflammatory M2 phenotype and inhibition of neuronal death.

Recurrent Generalized Seizures with Postictal Todd’s Paralysis Caused by Medication-Associated Severe Hypomagnesemia: A Case Report

Hypomagnesemia is one of the electrolyte disturbances that can cause seizures. It is common in the hospitalized patients and can be induced by long-term usage of many medications. A 68-year-old male known to have hypertension and gastroesophageal reflux presented to the Emergency Department with an unprovoked first seizure at home followed by a temporary right-sided hemiparesis, dysphasia, and facial asymmetry. The hemiparesis, dysphasia, and facial asymmetry resolved within less than an hour after the seizure. His serum potassium was low with prolonged QT interval in the electrocardiogram (serum magnesium was not checked in the Emergency Department). He received intravenous IV potassium chloride infusion, and his serum potassium level was corrected, but he had a recurrent seizure after 10 h. At that time, his serum magnesium was found to be very low, he received IV magnesium sulfate infusion, and his indapamide, omeprazole, and metformin medications were stopped. He had no further seizures, the rest of his blood tests were normal, and his CT brain was unremarkable. He was treated for aspiration pneumonia, and his outpatient MRI brain and EEG came to be normal too.

PURA-Related Developmental and Epileptic Encephalopathy

Background and ObjectivesPurine-rich element-binding protein A (PURA) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients.MethodsData on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained.ResultsA cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations.DiscussionThe PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations.