Magnetic resonance imaging fingerprints of status epilepticus: A case-control study.

OBJECTIVE: Status epilepticus (SE) is frequently associated with peri-ictal magnetic resonance imaging (MRI) abnormalities (PMA). However, the anatomical distribution of these alterations has not been systematically studied. The aim of this study was to assess the localization patterns of PMA in patients with SE. METHODS: In this prospective case-control study, we compared the distribution and combinations of diffusion-restricted PMA to diffusion-restricted lesions caused by other neurological conditions. All patients of the SE group and the control group underwent MRI including a diffusion-weighted imaging sequence. Patients with SE were imaged within 48 h after its onset. RESULTS: We enrolled 201 patients (51 with SE and 150 controls). The most frequent locations of PMA in SE were cortex (25/51, 49%), followed by hippocampus (20/51, 39%) and pulvinar of thalamus (10/51, 20%). In the control group, the cortex was involved in 80 of 150 (53%), white matter in 53 of 150 (35%), and basal ganglia in 33 of 150 (22%). In the control group, the pulvinar of thalamus was never affected and hippocampal structures were rarely involved (7/150, 5%). Involvement of the pulvinar of thalamus and the hippocampus had high specificity for SE at 100% (95% confidence interval [CI] = 98-100) and 95% (95% CI = 91-98), respectively. The sensitivity, however, was low for both locations (pulvinar of thalamus: 20%, 95% CI = 10-33; hippocampus: 39%, 95% CI = 26-54). SIGNIFICANCE: Diffusion-restricted MRI lesions observed in the pulvinar of thalamus and hippocampus are strongly associated with SE. These changes may help physicians in diagnosing SE-related changes on MRI in an acute setting, especially in cases of equivocal clinical and electroencephalographic manifestations of SE.

Post-hypoxic status epilepticus - A distinct subtype of status epilepticus with poor prognosis.

OBJECTIVE: To evaluate the clinical outcome of patients with possible and definitive post-hypoxic status epilepticus (SE) and to describe the SE types in patients with definitive post-hypoxic SE. METHODS: Patients with definitive or possible SE resulting from hypoxic brain injury after cardiac arrest (CA) were prospectively recruited. Intermittent EEG was used for the diagnosis of SE according to clinical practice. Two raters blinded to outcome analyzed EEGs retrospectively for possible and definitive SE patterns and background features (frequency, continuity, reactivity, and voltage). Definitive SE was classified according to semiology (ILAE). Mortality and Cerebral Performance Categories (CPC) score were evaluated 1 month after CA. RESULTS: We included 64 patients of whom 92% died. Among the survivors, only one patient had a good neurological outcome (CPC 1). No patient survived with a burst suppression pattern, low voltage, or electro-cerebral silence in any EEG. Possible or definitive SE was diagnosed in a median of 47 h (IQR 39-72 h) after CA. EEG criteria for definitive electrographic SE were fulfilled in 39% of patients; in 38% - for electroclinical SE and in 23% - for ictal-interictal continuum (IIC). The outcome did not differ significantly between the three groups. The only patient with good functional outcome belonged to the IIC group. Comatose non-convulsive SE (NCSE) without subtle motor phenomenon occurred in 20% of patients with definitive electrographic SE and outcome was similar to other types of SE. SIGNIFICANCE: Possible or definitive SE due to hypoxic brain injury is associated with poor prognosis. The outcome of patients with electrographic SE, electroclinical SE, and IIC did not differ significantly. Outcome was similar in patients with definitive electrographic SE with and without prominent motor features.

Intravenous topiramate for seizure emergencies - First in human case report.

Topiramate (TPM) is widely used in focal and generalized epilepsies. It is commercially available as tablets and sprinkles capsules for oral treatment. Previous studies comparing intravenous (IV) to oral TPM in healthy adults showed more rapid pharmacodynamic effects in cases of IV administration. Despite promising findings, no clinical application in humans followed. We present a case of a pregnant woman with idiopathic generalized epilepsy who experienced a generalized tonic-clonic seizure in the third trimenon due to low TPM levels attributed to pregnancy followed by repeated prolonged absences. We applied a new meglumine-based solution (1%) of TPM (10 mg/ml) in two IV infusions of 200 mg each under EEG monitoring over a total duration of 1 hour. The infusion was well tolerated and led to a rapid increase in plasma TPM levels. A clinical as well as electroencephalographic improvement was documented within the first hours. To the best available knowledge, this is the first reported case where IV TPM was used therapeutically for seizure treatment in humans. It is also the first time that the new meglumine-based solution was used in a human with epilepsy. The advantages of IV route delivery and the solution's quick preparation, high tolerability, and low toxicity make it ideal for use in many clinical settings and high-care patients. IV TPM seems to be a reasonable adjunctive option for adults with seizures, previously stabilized on oral TPM, who need rapid plasma concentration boosting. Although our experience was successful in using injectable TPM in seizure emergencies, randomized controlled clinical trials are required to make recommendations for the use of IV TPM on patients with epilepsy. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022 in Salzburg, Austria.

Imaging of status epilepticus: Making the invisible visible. A prospective study on 206 patients.

BACKGROUND: Peri-ictal MRI abnormalities (PMA) frequently affect the cerebral cortex, hippocampus, pulvinar of the thalamus, corpus callosum, and cerebellum. In this prospective study, we aimed to characterize the spectrum of PMA in a large cohort of patients with status epilepticus. METHODS: We prospectively recruited 206 patients with SE and an acute MRI. The MRI protocol included diffusion weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), arterial spin labeling (ASL), and T1-weighted imaging pre-and post-contrast application. Peri-ictal MRI abnormalities were stratified as either neocortical or non-neocortical. Amygdala, hippocampus, cerebellum, and corpus callosum were regarded as non-neocortical structures. RESULTS: Peri-ictal MRI abnormalities were observed in 93/206 (45%) of patients in at least one MRI sequence. Diffusion restriction was observed in 56/206 (27%) of patients, which was mainly unilateral in 42/56 (75%) affecting neocortical structures in 25/56 (45%), non-neocortical structures in 20/56 (36%) and both areas in 11/56 (19%) of patients. Cortical DWI lesions were located mostly in frontal lobes 15/25 (60%); non-neocortical diffusion restriction affected either the pulvinar of the thalamus or hippocampus 29/31 (95%). Alterations in FLAIR were observed in 37/203 (18%) of patients. They were mainly unilateral 24/37 (65%); neocortical 18/37 (49%), non-neocortical 16/37 (43%), or affecting both neocortical and non-neocortical structures 3/37 (8%). In ASL, 51/140 (37%) of patients had ictal hyperperfusion. Hyperperfused areas were located mainly in the neocortex 45/51 (88%) and were unilateral 43/51 (84%). In 39/66 (59%) of patients, PMA were reversible in one week. In 27/66 (41%), the PMA persisted and a second follow-up MRI was performed three weeks later in 24/27 (89%) patients. In 19/24 (79%) PMA were resolved. CONCLUSIONS: Almost half of the patients with SE had peri-ictal MRI abnormalities. The most prevalent PMA was ictal hyperperfusion followed by diffusion restriction and FLAIR abnormalities. Neocortex was most frequently affected especially the frontal lobes. The majority of PMAs were unilateral. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Quantitative Analysis of Diffusion-Restricted Lesions in a Differential Diagnosis of Status Epilepticus and Acute Ischemic Stroke.

Background and Purpose: Distinction between acute ischemic stroke (AIS) and status epilepticus (SE) on MRI can be challenging as restricted diffusion may occur in both conditions. In this study, we aimed to test a tool, which could help in differentiating AIS from SE when restricted diffusion was present on MRI. Materials and Methods: In diffusion weighted imaging (DWI) with a b-value of 1,000 and apparent diffusion coefficient (ADC) maps, we compared the ratios of intensities of gray values of diffusion-restricted lesions to the healthy mirror side in patients with AIS and SE. Patients were recruited prospectively between February 2019 and October 2021. All patients underwent MRI and EEG within the first 48 h of symptom onset. Results: We identified 26 patients with SE and 164 patients with AIS. All patients had diffusion-restricted lesions with a hyperintensity in DWI and ADC signal decrease. Diffusion restriction was significantly more intense in patients with AIS as compared to patients with SE. The median ratios of intensities of gray values of diffusion-restricted lesions to the healthy mirror side for DWI were 1.42 (interquartile range [IQR] 1.32-1.47) in SE and 1.67 (IQR 1.49-1.90) in AIS (p < 0.001). ADC decrease was more significant in AIS as compared to SE with median ratios of 0.80 (IQR 0.72-0.89) vs. 0.61 (IQR 0.50-0.71), respectively (p < 0.001). A cutoff value for ratios of DWI signal was 1.495 with a sensitivity of 75% and a specificity of 85%. Values lower than 1.495 were more likely to be associated with SE and higher values were with AIS. A cutoff value for ADC ratios was 0.735 with a sensitivity of 73% and a specificity of 84%. Values lower than 0.735 were more likely to be associated with AIS and higher values were with SE. Conclusion: Diffusion restriction and ADC decrease were significantly more intense in patients with AIS as compared to SE. Therefore, quantitative analysis of diffusion restriction may be a helpful tool for differentiating between AIS and SE when restricted diffusion is present on MRI.

Post-COVID 19 neurological syndrome: Implications for sequelae's treatment.

Study design Literature review. OBJECTIVES: Describe the implications of post-COVID syndrome due to neurological sequelae including treatment and the differences that may exist between this group of patients and those who present these events not associated with COVID-19. METHODS: A non-systematic review of the literature was carried out in PubMed and Science Direct databases, using the keywords "Post-acute COVID-19 syndrome"; "Neurological complications"; "Neurologic Manifestations" "COVID-19″ and "Rehabilitation", as well as synonyms, which were combined with the operators "AND" and "OR". RESULTS: The COVID-19 viral caustive agent, SARS-CoV-2, has a high affinity for human angiotensin-converting enzyme 2 receptor on type II pneumocytes. This receptor is also expressed in neurons and glial cells. Based on the foregoing and other not so clear mechanisms, it is stated that SARS-CoV-2 has tropism for the nervous system, being evident through the neurological manifestations observed in patients with mild, moderate and severe phenotype of the disease such as anosmia, ageusia, headache, cerebrovascular accidents, Guillain-Barré syndrome, seizures, and encephalopathy. This can generate severe sequelae and even fatal outcomes in those affected. CONCLUSIONS: Neurological complications caused by COVID-19 are frequent and represent a risk that compromises the functional capacity and the life of patients. The suspicion of these conditions, the strict control of metabolic alterations and cardiovascular risk factors, the effective and safe treatment of these entities, are a current challenge throughout the pandemic. The rehabilitation process in these patients is a challenge. This is due to the limitations generated by multi-organ damage, as well as risk of brain death.

Status epilepticus admissions during the COVID-19 pandemic in Salzburg-A population-based study.

Several emergencies were admitted less frequently to the hospital during the coronavirus disease 2019 (COVID-19) pandemic. To investigate whether this also occurred with status epilepticus (SE) we compared admissions due to first SE from March to April 2020 ("Time of COVID," TOC) with January to February 2020 ("pre-COVID," preCOV). We also compared admission numbers in TOC and preCOV with the respective 2-month periods in 2018 and 2019 in a retrospective cohort analysis. Two investigators independently searched the hospital patient database for various forms of SE. There was no significant change in the 2-month incidences of first SE in the city of Salzburg from preCOV of 6.1 (95% confidence interval [CI] 2.9-12.3) to TOC of 6.9/100 000 adults (95% CI 3.4-13.3). Admission numbers did not differ significantly from previous years. Estimated adjusted incidence was in line with a recent 5-year epidemiological study in Salzburg. However, a trend toward less-frequent nonconvulsive SE (NCSE) and loss of female predominance were indirect hints of underdiagnosing SE. In contrast to other medical conditions, SE most often presents clinically with impaired consciousness, which may promote admission to emergency departments even in times of lock-down. Further research of medical support of women and patients with NCSE during pandemic-related restrictions is warranted.

Relationship between the history of cerebrovascular disease and mortality in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Past history of stroke has been associated with an increased risk of a new ischemic stroke. Several studies have indicated increased prevalence of strokes among coronavirus patients. However, the role of past history of stroke in COVID19 patients is still unclear. The purpose of this systematic review is to evaluate and summarize the level of evidence on past history of stroke in COVID19 patients. METHODS: A systematic review was performed according to the PRISMA guidelines was performed in PubMed, Embase, EBSCO Host, Scopus, Science Direct, Medline, and LILACS. Eligibility criteria: We evaluated studies including patients with diagnosis of COVID 19 and a past history of stroke. Risk of bias: was evaluated with the Newcastle- Ottawa Scale (NOS) and experimental studies were evaluated using the ROBINS-I scale. RESULTS: Seven articles out of the total 213 articles were evaluated and included, involving 3244 patients with SARS VOC 2 Disease (COVID19) of which 198 had a history of cerebrovascular disease. Meta-analysis of the data was performed, observing an increase in mortality in patients with a history of cerebrovascular disease compared to those with different comorbidities or those without underlying pathology (OR 2.78 95 % CI [1.42-5.46] p = 0.007; I2 = 49 %) showing adequate heterogeneity. The presence of publication bias was evaluated using the Egger test in a funnel plot, showing adequate. Asymmetry, indicating that there is no publication bias; however, due to the low number of included studies, we could not rule out or confirm the presence of bias. CONCLUSIONS: The history of cerebrovascular disease was associated with a 2.78-fold increased risk of mortality compared to patients with other comorbidities or without underlying pathologies.

Tonic status epilepticus in a centenarian woman.

Generalized tonic status epilepticus (TSE) is a rare epileptic condition. It occurs usually in the context of symptomatic generalized epilepsy, in particular, in subjects with a diagnosis of Lennox-Gastaut syndrome, atypical forms of idiopathic (genetic) generalized epilepsy, or as a paradoxical effect during treatment with diverse antiepileptic drugs. Herein, we describe the case of an elderly woman on chronic treatment with psychotropic drugs who developed an episode of generalized TSE. Motor manifestations were subtle and difficult to recognize as seizures, and a detailed video-EEG importantly contributed to accurate and prompt diagnosis. TSE was initially refractory to conventional anti-seizure drug therapy including levetiracetam and valproate but was finally controlled with lacosamide. Our case indicates a potential therapeutic effect of lacosamide on TSE in the elderly after treatment failure with first-line anti-seizure drugs. [Published with video sequence on www.epilepticdisorders.com].

Infectious agents and amyotrophic lateral sclerosis: another piece of the puzzle of motor neuron degeneration.

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons (MN). This fatal disease is characterized by progressive muscle wasting and lacks an effective treatment. ALS pathogenesis has not been elucidated yet. In a small proportion of ALS patients, the disease has a familial origin, related to mutations in specific genes, which directly result in MN degeneration. By contrast, the vast majority of cases are though to be sporadic, in which genes and environment interact leading to disease in genetically predisposed individuals. Lately, the role of the environment has gained relevance in this field and an extensive list of environmental conditions have been postulated to be involved in ALS. Among them, infectious agents, particularly viruses, have been suggested to play an important role in the pathogenesis of the disease. These agents could act by interacting with some crucial pathways in MN degeneration, such as gene processing, oxidative stress or neuroinflammation. In this article, we will review the main studies about the involvement of microorganisms in ALS, subsequently discussing their potential pathogenic effect and integrating them as another piece in the puzzle of ALS pathogenesis.

The increasing importance of environmental conditions in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons (MNs). Although a small percentage of ALS has a familial origin, the vast majority of cases are sporadic in which genetic factors and environment interact with each other leading to disease onset in genetically predisposed individuals. In the current model of the disease, each individual has a determined genetic load, some degree of cell degeneration related to age and several risky environmental exposures. In this scenario, MN degeneration would occur when the sum of these factors reach a certain threshold. To date, an extensive list of environmental factors has been associated to ALS, including different categories, such as exposure to heavy metals and other toxicants, cyanotoxins or infectious agents. In addition, in recent years, lifestyle and other demographic parameters are gaining relevance in the genesis of the disease. Among them, physical activity, nutrition, body mass index, cardiovascular risk factors, autoimmune diseases and cancer are some of the conditions which have been related to the disease. In this review, we will discuss the potential mechanisms of environmental conditions in motor neuron degeneration. Understanding the role of each one of these factors as well as their interactions appears as a crucial step in order to develop new preventive, diagnostic and therapeutic approaches for ALS patients.

Super-refractory nonconvulsive status epilepticus due to self-poisoning with metaldehyde.

INTRODUCTION: Metaldehyde self-poisoning in adults is uncommon and, to the best of our knowledge, an episode of super-refractory nonconvulsive status epilepticus (sr-NCSE) following an suicide attempt has not been previously demonstrated. CASE REPORT: A 68-year-old woman was admitted to our Intensive Care Unit (ICU) in coma. On neurologic examination, the pupils were reactive, brainstem reflexes were present and plantar responses were flexor bilaterally. Routine laboratory tests were unremarkable. Arterial blood gas analysis revealed a mixed acidosis. A computed tomography (CT) scan of the brain and angio-CT were normal. The family confirmed that the patient had had suicidal ideation, and they had discovered a bag of slug killer (metaldehyde 5%) in her room. Two hours after the admission at the ICU, her neurological state remained unchanged. Sedation with intravenous propofol and antiepileptic therapy with levetiracetam (1000 mg/24 h) were started. The next day, propofol infusion was stopped but the level of consciousness of the patient did not improve. A video-electroencephalograhy (v-EEG) showed continuous generalized paroxysms of spike-wave and sharp-slow wave complexes compatible with the diagnosis of generalized NCSE. On day 3, the episode of NCSE was controlled. Finally, 15 days after ICU admission she was discharged with a normal neurological examination. CONCLUSION: This clinical case highlights that in comatose patients as consequence of metaldehyde poisoning, a v-EEG evaluation should be perform in order to rule out the existence of NCSE.