Amongst the neurologic complications of COVID-19 disease, very few reports have shown the presence of the virus in the cerebrospinal fluid (CSF). Seizure and rarely status epilepticus can be associated with COVID-19 disease. Here we present a 73-year-old male with prior history of stroke who has never experienced seizure before. He had no systemic presentation of COVID-19 disease. The presenting symptoms were two consecutive generalized tonic-clonic seizures that after initial resolution turned into a nonconvulsive status epilepticus despite antiepileptic treatment (a presentation similar to NORSE (new-onset refractory status epilepticus)). There was no new lesion in the brain magnetic resonance imaging (MRI). The CSF analysis only showed an increased protein levels and positive reverse transcription polymerase chain reaction (RT-PCR) of 2019-nCoV. Patient recovered partially after anesthetic, IVIG, steroid, and remdesivir. To our knowledge, this is the first report of a refractory status epilepticus with the presence of SARS-CoV-2 ribonucleic acid (RNA) in the CSF.

Epilepsy is one of the most common brain disorders, affecting more than 50 million people worldwide. Although its treatment is currently symptomatic, the last generation of anti-seizure drugs is characterized by better pharmacokinetic profiles, efficacy, tolerability and safety. Lacosamide is a third-generation anti-seizure drug that stands out due to its good efficacy and safety profile. It is used with effectiveness in the treatment of partial-onset seizures with or without secondary generalization, primary generalized tonic-clonic seizures and off-label in status epilepticus. Despite scarcely performed until today, therapeutic drug monitoring of lacosamide is proving to be advantageous by allowing the control of inter and intra-individual variability and promoting a successful personalized therapy, particularly in special populations. Herein, the pharmacology, pharmacokinetics, and clinical data of lacosamide were reviewed, giving special emphasis to the latest molecular investigations underlying its mechanism of action and therapeutic applications in pathologies besides epilepsy. In addition, the pharmacokinetic characteristics of lacosamide were updated, as well as current literature concerning the high pharmacokinetic variability observed in special patient populations and that must be considered during treatment individualization.

An 87-year-old woman was admitted to our hospital because of speech disturbance and right facio-pharyngo-glosso-masticatory diplegia. She had bronchial asthma, was previously diagnosed with cerebral infarction, had experienced two events of convulsive status epilepticus, and was undergoing treatment with theophylline, levetiracetam, and clopidogrel. Head diffusion-weighted magnetic resonance imaging revealed a high-signal area in the left crus posterior capsula interna. For this, we administered cilostazol along with her regular medicines. On day 14, she had tonic-clonic convulsions, extending from the right upper and lower limbs to the whole body. Subsequently, cilostazol was discontinued, and the dose of levetiracetam was increased. However, she developed severe tonic-clonic seizures with right sensory aphasia and right hemiplegia, for which an increased dose of lacosamide was added. When theophylline was discontinued 5 days after the onset of convulsions, the blood concentration of theophylline was 9.7μg/mL. After theophylline was discontinued, tonic-clonic convulsions improved. The disturbance of consciousness and right hemiparesis were improved after one week, while the disturbance of sensory aphasia was improved after one month. We suspect that cerebral infarction may have aggravated the central nervous system damage caused by theophylline, thereby resulting in aminophylline-related non-convulsive status epilepticus. (Received 20 July 2020; Accepted 27 October 2020; Published 1 March 2021).

Seizure clusters, an intermediate between single seizure and status epilepticus, are associated with morbidity, impaired quality of life, and premature mortality. The relationship between seizure clusters and sudden unexplained death in epilepsy (SUDEP) is poorly understood. Here, we define seizure clusters; review comorbid psychiatric disorders and memory deficits associated with seizure clusters; and review cases of witnessed SUDEP for which seizure frequency prior to death is available. Patients with a history of seizure clusters have a 2.5 fold increased risk for SUDEP, and one third of patients with monitored in hospital SUDEP experienced a cluster of generalized tonic clonic seizures prior to death. Understanding the effects of seizure frequency and duration on SUDEP risk could yield new insights in SUDEP pathophysiology and new targets for intervention.

Uncontrolled repetitive generalized tonic-clonic seizures (GTCS) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). GTCS can be observed in models such as Pentylenetetrazole kindling (PTZ-K) or pilocarpine-induced Status Epilepticus (SE-P), which share similar alterations in cardiac function, with a high risk of SUDEP. Terminal cardiac arrhythmia in SUDEP can develop as a result of a high rate of hypoxic stress-induced by convulsions with excessive sympathetic overstimulation that triggers a neurocardiogenic injury, recently defined as "Epileptic Heart" and characterized by heart rhythm disturbances, such as bradycardia and lengthening of the QT interval. Recently, an iron overload-dependent form of non-apoptotic cell death called ferroptosis was described at the brain level in both the PTZ-K and SE-P experimental models. However, seizure-related cardiac ferroptosis has not yet been reported. Iron overload cardiomyopathy (IOC) results from the accumulation of iron in the myocardium, with high production of reactive oxygen species (ROS), lipid peroxidation, and accumulation of hemosiderin as the final biomarker related to cardiomyocyte ferroptosis. Iron overload cardiomyopathy is the leading cause of death in patients with iron overload secondary to chronic blood transfusion therapy; it is also described in hereditary hemochromatosis. GTCS, through repeated hypoxic stress, can increase ROS production in the heart and cause cardiomyocyte ferroptosis. We hypothesized that iron accumulation in the "Epileptic Heart" could be associated with a terminal cardiac arrhythmia described in the IOC and the development of state-potentially in the development of SUDEP. Using the aforementioned PTZ-K and SE-P experimental models, after SUDEP-related repetitive GTCS, we observed an increase in the cardiac expression of hypoxic inducible factor 1α, indicating hypoxic-ischemic damage, and both necrotic cells and hemorrhagic areas were related to the possible hemosiderin production in the PTZ-K model. Furthermore, we demonstrated for the first time an accumulation of hemosiderin in the heart in the SE-P model. These results suggest that uncontrolled recurrent seizures, as described in refractory epilepsy, can give rise to high hypoxic stress in the heart, thus inducing hemosiderin accumulation as in IOC, and can act as an underlying hidden mechanism contributing to the development of a terminal cardiac arrhythmia in SUDEP. Because iron accumulation in tissues can be detected by non-invasive imaging methods, cardiac iron overload in refractory epilepsy patients could be treated with chelation therapy to reduce the risk of SUDEP.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare prion disease that causes rapidly progressive fatal neurodegeneration. The rarer Heidenhain variant of sCJD presents with visual symptoms and is rarely reported in the literature from sub-Saharan Africa. We report the case of a 57-year-old male with a three-week history of losing direction when driving home and visual hallucinations described as seeing rainbows. Magnetic resonance imaging (MRI) of the brain revealed unilateral parieto-occipital sulcal hyperintensities with restriction on diffusion-weighted imaging (DWI), and electroencephalography (EEG) showed right para-central slowing leading to an initial diagnosis of non-convulsive status epilepticus. He was treated with anti-epileptic medication but was re-admitted less than a month later with worsening spatial memory, aggression, ataxia, dysarthria, myoclonic jerks and a positive startle response, later developing generalised tonic-clonic seizures. Repeat MRI brain scan showed widespread posterior-predominant sulcal DWI restriction in a cortical ribboning pattern pathognomonic for sCJD. EEG showed diffuse slowing, and cerebrospinal fluid was analyzed for abnormal prion protein using real-time quaking-induced conversion but was inconclusive due to suboptimal sample collection. The patient fulfilled the diagnostic criteria for probable sCJD, Heidenhain variant; the family declined brain biopsy for definitive diagnosis. He was subsequently palliated at a local hospice where he died approximately three months after the onset of symptoms. Our case highlights the presence of a rare form of sCJD, and the diagnostic challenges faced in our resource-limited setting.

A 2-year-old Bull Mastiff cross Boxer neutered male dog was evaluated because of 2-month history of non-progressive right head tilt and mild vestibular ataxia. MRI of the brain revealed a faint T2W, FLAIR, DWI and ADC heterogenous hyperintense and T1W isointense intra-axial lesion with indistinct margins at the level of the pons and medulla oblongata. The lesion did not show any susceptibility artefact on T2* GRE images or contrast enhancement and CSF analysis was normal. Analysis of the spectra from MRS of the thalamus not promptly available at the time of the MRI study revealed a decreased level of NAA, as seen in people with gliomatosis cerebri. The dog represented 3 weeks later and, on this occasion, displayed left-sided head tilt, left-sided postural reaction deficits and near-syncopal episodes associated with state of confusion. Repeated MRI revealed a larger non-enhancing intra-axial lesion with a more hyperintense signal than previously described. CSF was normal and PCR of CSF for infectious diseases was negative. Thoracic and abdominal computed tomography did not reveal any primary or metastatic process. Immunosuppressive treatment was attempted and the dog remained stable over 5 days, then developed generalized tonic-clonic seizures which led to status epilepticus and death. Histopathology supported the diagnosis of gliomatosis cerebri. Gliomatosis cerebri remains difficult to diagnose ante-mortem, due to the broad age of onset and the variable duration and wide range of clinical signs. The mismatch between MRI findings and clinical presentation, the fluctuating clinical signs with near-syncopal episodes associated with a state of confusion, the presence of an infiltrative brain disease as depicted on MR imaging and a normal CSF analysis, should prompt the clinician to consider possible diagnosis of a widespread infiltrative neoplasm. Although, MRS may help narrow the differential diagnosis in favor of a neoplastic lesion, the overall prognosis remains poor.

LMR-101 is a bisphenol derivative of propofol, a short-acting general anesthetic, which is also used to manage status epilepticus (SE). We evaluated the sedative and anticonvulsant effects of LMR-101 to discover its potential to manage epilepsy and SE in the clinic.

The global burden of seizure disorders is apparent and necessitates the effective management of patients with status epilepticus (SE). The goal of management is universally accepted as the prompt mitigation of seizure activity with appropriate supportive care. During management, patients may require intubation. In the process of endotracheal tube placement, patients are administered neuromuscular blockers and general anesthesia. Paralytic activity on the neuromuscular junction hinders the emergency physician's ability to effectively observe seizure activity. Moreover, little can be discerned about patient sedation levels for titration. Effective tourniquet placement may be used to separate a region of the body from general circulation, rendering distal tissues unaffected by neuromuscular blockade.

We present a case study of a 67-year-old man who presented with a new onset of recurrent tonic-clonic seizures. He had tested positive to gamma-aminobutyric acid B receptor antibodies in his blood and cerebrospinal fluid, and subsequent CT imaging and transrectal biopsy confirmed the presence of a locally advanced mixed small cell and Gleason 9 adenocarcinoma of the prostate. His seizures remained resistant to treatment with multiple antiepileptic drugs, including sodium valproate, clobazam, topiramate, carbamazepine, phenytoin and lacosamide. He progressed to status epilepticus, which required intravenous immunoglobulin and steroids, followed by plasma exchange 1 week later. The status epilepticus was refractory and required multiple admissions to the intensive care unit.

The NEXMIF (KIAA2022) gene is located in the X chromosome, and hemizygous mutations in NEXMIF cause X-linked intellectual disability in male patients. Female patients with heterozygous mutations in NEXMIF also show similar, but milder, intellectual disability. Most female patients demonstrate intractable epilepsy compared with male patients, and the treatment strategy for epilepsy is still uncertain. Thus far, 24 female patients with NEXMIF mutations have been reported. Of these 24 patients, 20 also have epilepsy. Until now, epilepsy has been controlled in only 2 of these female patients. We report a female patient with a heterozygous de novo mutation, NM_001008537.2:c.1123del (p.Glu375Argfs*21), in NEXMIF. The patient showed mild intellectual disability, facial dysmorphism, obesity, generalized tonic-clonic seizures, and nonconvulsive status epilepticus. Sodium valproate was effective but caused secondary amenorrhea. We successfully treated her epilepsy with clonazepam without side effects, indicating that clonazepam might be a good choice to treat epilepsy in patients with NEXMIF mutations.

Background: Little is known about idiopathic Epilepsy in Greater Swiss Mountain Dogs. Until now this breed is not listed as a predisposed breed for idiopathic epilepsy. The aim of this study was to estimate the prevalence of idiopathic epilepsy in Greater Swiss Mountain Dogs in Switzerland and to describe the clinical characteristics of epilepsy in this breed including seizures semiology and response to treatment. Material and Methods: Records of the Swiss Kennel Club for Greater Swiss Mountain Dogs were searched for reported cases of epileptic seizures between 1999-2019. The total number of reported cases and the signalment was reviewed. Furthermore, all owners of Greater Swiss Mountain Dogs registered to the breeding club were invited to complete an online questionnaire. Results: In total 600 Greater Swiss Mountain Dog's live in Switzerland: 70-90 puppies are born each year. Between 1999 and 2019 34 dogs (2%) were announced with seizures. Of the 400 owners invited to answer the questionnaire 128 completed the questionnaire. 20 of these 128 dogs were suffering from idiopathic epilepsy. The prevalence for idiopathic epilepsy based on the questionnaire was therefore 15,6%. All affected dogs showed generalized tonic-clonic seizures. Cluster seizures and status epilepticus occurred in 5 (41,6%) and 6 (50%) of the dogs. Long term seizure control was only achieved in 10% of the dogs. Five dogs (25%) died or were euthanized because of insufficient seizure control. Only one dog (5%) showed clinical remission. Conclusion: Prevalence of idiopathic epilepsy is higher in Greater Swiss Mountain Dogs in Switzerland compared to the general dog population. Seizure control seems to be difficult to achieve in this breed and remission-rate is low.

To characterize neocortical onset status epilepticus (SE) in the C57BL/6J mouse.

Autosomal recessive pathogenic variants of the SLC13A5 gene are associated with severe neonatal epilepsy, developmental delay, and tooth hypoplasia/hypodontia. We report on 14 additional patients and compare their phenotypic features to previously published patients to identify the clinical hallmarks of this disorder.

To ascertain factors that are related to the antiepileptic drug load in epilepsy.