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.

Iatrogenic cerebral amyloid angiopathy: A multinational case series and individual patient data analysis of the literature.

BACKGROUND: The transmission of amyloid ß (Aß) in humans leading to iatrogenic cerebral amyloid angiopathy (iCAA) is a novel concept with analogies to prion diseases. However, the number of published cases is low, and larger international studies are missing. AIMS: We aimed to build a large multinational collaboration on iCAA to better understand the clinical spectrum of affected patients. METHODS: We collected clinical data on patients with iCAA from Austria, Croatia, Italy, Slovenia, and Spain. Patients were included if they met the proposed Queen Square diagnostic criteria (QSC) for iCAA. In addition, we pooled data on disease onset, latency, and cerebrospinal fluid (CSF) biomarkers from previously published iCAA cases based on a systematic literature review. RESULTS: Twenty-seven patients (22% women) were included in this study. Of these, 19 (70%) met the criteria for probable and 8 (30%) for possible iCAA. Prior neurosurgical procedures were performed in all patients (93% brain surgery, 7% spinal surgery) at median age of 8 (interquartile range (IQR) = 4-18, range = 0-26 years) years. The median symptom latency was 39 years (IQR = 34-41, range = 28-49). The median age at symptom onset was 49 years (IQR = 43-55, range = 32-70). Twenty-one patients (78%) presented with intracranial hemorrhage and 3 (11%) with seizures. CONCLUSIONS: Our large international case series of patients with iCAA confirms a wide age boundary for the diagnosis of iCAA. Dissemination of awareness of this rare condition will help to identify more affected patients.

Role of Magnesium in the Intensive Care Unit and Immunomodulation: A Literature Review.

Both the role and the importance of magnesium in clinical practice have grown considerably in recent years. Emerging evidence suggests an association between loss of magnesium homeostasis and increased mortality in the critical care setting. The underlying mechanism is still unclear, but an increasing number of in vivo and in vitro studies on magnesium's immunomodulating capabilities may shed some light on the matter. This review aims to discuss the evidence behind magnesium homeostasis in critically ill patients, and its link with intensive care unit mortality via a likely magnesium-induced dysregulation of the immune response. The underlying pathogenetic mechanisms, and their implications for clinical outcomes, are discussed. The available evidence strongly supports the crucial role of magnesium in immune system regulation and inflammatory response. The loss of magnesium homeostasis has been associated with an elevated risk of bacterial infections, exacerbated sepsis progression, and detrimental effects on the cardiac, respiratory, neurological, and renal systems, ultimately leading to increased mortality. However, magnesium supplementation has been shown to be beneficial in these conditions, highlighting the importance of maintaining adequate magnesium levels in the intensive care setting.

Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review.

Brain tumor-related epilepsy (BTRE) is a common comorbidity in patients with brain neoplasms and it may be either the first symptom or develop after the tumor diagnosis. Increasing evidence suggests that brain tumors and BTRE share common pathophysiological mechanisms. Glutamatergic mechanisms can play a central role in promoting both primary brain tumor growth and epileptogenesis. Perampanel (PER), which acts as a selective antagonist of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, may play a role both in the reduction in tumor growth and the control of epileptiform activity. This systematic review aimed to summarize the pre-clinical and clinical evidence about the antitumor properties, antiseizure effects and tolerability of PER in BTRE. Eight pre-clinical and eight clinical studies were identified. The currently available evidence suggests that PER can be an effective and generally well-tolerated therapeutic option in patients with BTRE. In vitro studies demonstrated promising antitumor activity of PER, while no role in slowing tumor progression has been demonstrated in rat models; clinical data on the potential antitumor activity of PER are scarce. Additional studies are needed to explore further the effects of PER on tumor progression and fully characterize its potentialities in patients with BTRE.

Efficacy and Safety of Fenfluramine in Epilepsy: A Systematic Review and Meta-analysis.

INTRODUCTION: Fenfluramine (FFA) is an amphetamine derivative that promotes the release and blocks the neuronal reuptake of serotonin. Initially introduced as an appetite suppressant, FFA also showed antiseizure properties. This systematic review aimed to assess the efficacy and safety of FFA for the treatment of seizures in patients with epilepsy. METHODS: We systematically searched (in week 3 of June 2022) MEDLINE, the Cochrane Central Register of Controlled Trials, and the US National Institutes of Health Clinical Trials Registry. Randomized, double- or single-blinded, placebo-controlled studies of FFA in patients with epilepsy and uncontrolled seizures were identified. Efficacy outcomes included the proportions of patients with ≥ 50% and 100% reductions in baseline seizure frequency during the treatment period. Tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and suffered adverse events (AEs). The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. The risk ratio (RR) along with the 95% confidence interval (CI) were estimated for each outcome. RESULTS: Three trials were identified and a total of 469 Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) subjects were randomized. All three trials were judged to be at low risk of biases. In patients with DS, the RRs for ≥ 50% and 100% reductions in convulsive seizure frequency for the FFA group compared to placebo were 5.61 (95% CI 2.73-11.54) and 4.71 (95% CI 0.57-39.30), respectively. In patients with LGS, the corresponding RRs for ≥ 50% and 100% reductions in drop seizure frequency were 2.58 (95% CI 1.33-5.02) and 0.50 (95% CI 0.031-7.81), respectively. The drug was withdrawn for any reason in 10.1% and 5.8% of patients receiving FFA and placebo, respectively (RR 1.79, 95% CI 0.89-3.59). Treatment discontinuation due to AEs occurred in 5.4% and 1.2% of FFA- and placebo-treated patients, respectively (RR 3.63, 95% CI 0.93-14.16). Decreased appetite, diarrhoea, fatigue, and weight loss were AEs associated with FFA treatment. CONCLUSION: Fenfluramine reduces the frequency of seizures in patients with DS and LGS. Decreased appetite, diarrhoea, fatigue, and weight loss are non-cardiovascular AEs associated with FFA.

Epilepsy in cerebral amyloid angiopathy: an observational retrospective study of a large population.

OBJECTIVE: Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous intracranial hemorrhage in older adults. Epilepsy represents a possible sequela of the disease. To date, studies on epilepsy in CAA are lacking, and the few data available mainly focus on CAA-related inflammation (CAA-ri), the inflammatory form of the disease. METHODS: In this retrospective observational study, we consecutively recruited CAA patients observed over a time span of 10 years, collecting demographic, clinical, and instrumental data. Significant baseline characteristics were evaluated as potential risk factors for the development of epilepsy in the CAA population, and in the subgroups of CAA-ri and CAA without inflammatory reaction (CAA-nri). The effect of potential risk factors for epilepsy was measured as odds ratio with 95% confidence interval. RESULTS: Within 96 recruited CAA cases, 33 (34.4%) developed epilepsy during follow-up (median = 13.5 months). The prevalent type of seizure was focal (81.3%); 12.1% of the epileptic patients presented status epilepticus, and 6.1% developed drug-resistant epilepsy. Electroencephalographic traces revealed slow and epileptic discharge activity in the majority of epileptic patients, but also in those without epilepsy. The presence of focal or disseminated cortical superficial siderosis (cSS) was associated with an increased risk of epilepsy in the CAA-nri group, and the association with CAA-ri and epilepsy was present in the overall population. SIGNIFICANCE: Epilepsy is a common manifestation during the course of CAA, where CAA-ri and cSS represent predisposing factors for the development of seizures. These data suggest the importance of a deep characterization of CAA patients, to better select those more prone to develop epilepsy.

Vitamin D, Chronic Migraine, and Extracranial Pain: Is There a Link? Data From an Observational Study.

Several studies focused on the role of vitamin D (vitD) in pain chronification. This study focused on vitD level and pain chronification and extension in headache disorders. Eighty patients with primary headache underwent neurological examination, laboratory exams, including serum calcifediol 25(OH)D, and headache features assessment along with three questionnaires investigating depression, anxiety, and allodynia. The 86.8% of the population had migraine (48% episodic and 52% chronic). The 44.1% of patients had extracranial pain, and 47.6% suffered from allodynia. A vitD deficit, namely a serum 25(OH)D level <20 ng/ml, was detectable in 46.1% of the patients, and it occurred more frequently (p = 0.009) in patients suffering from chronic migraine (CM)-medication overuse migraine (MOH) (62.9%) than in episodic migraine (EM, 25.7%) or tension-type headache (TTH, 11.4%). The occurrence of extracranial pain and allodynia was higher in the CM-MOH than in the EM and in the TTH groups but was not related to the co-occurrence of vitD deficiency (Fisher's exact test p = 0.11 and p = 0.32, respectively). Our findings show that 25(OH)D deficit is also related to chronic headache, probably because of vitD anti-inflammatory and tolerogenic properties, reinforcing the idea of a neuroinflammatory mechanism underpinning migraine chronification.

Posterior reversible encephalopathy syndrome and COVID-19: A series of 6 cases from Lombardy, Italy.

Posterior reversible encephalopathy cases are increasingly being reported in patients affected by COVID-19, but the largest series so far only includes 4 patients. We present a series of 6 patients diagnosed with PRES during COVID-19 hospitalized in 5 Centers in Lombardia, Italy. 5 out of the 6 patients required intensive care assistence and seizures developed at weaning from assisted ventilation. 3 out of 6 patients underwent cerebrospinal fluid analysis which was normal in all cases, with negative PCR for Sars-CoV-2 genome search. PRES occurrence may be less rare than supposed in COVID-19 patients and a high suspicion index is warranted for prompt diagnosis and treatment.

An Example of a Stroke Unit Reshaping in the Context of a Regional Hub and Spoke System in the COVID-19 Era.

During the COVID-19 outbreak, the Neurology and Stroke Unit (SU) of the hospital of Varese had to serve as a cerebrovascular hub, meaning that the referral area for the unit doubled. The number of beds in the SU was increased from 4 to 8. We took advantage of the temporary suspension of the out-patient clinic and reshaped our activity to guarantee the 24/7 availability of recombinant tissue Plasminogen Activator (rtPA) intravenous therapy (IVT) in the SU, and to ensure we were able to admit patients to the SU as soon as they completed endovascular treatment (EVT). In 42 days, 46 stroke patients were admitted to our hospital, and 34.7% of them underwent IVT and/or EVT, which means that we treated 0.38 patients per day; in the baseline period from 2016 to 2018, these same figures had been 23.5% and 0.23, respectively. The mean values of the door-to-first CT/MRI and the door-to-groin puncture, but not of the onset-to-door and the door-to-needle periods were slightly but significantly longer than those observed in the baseline period in 276 patients. On an individual basis, only one patient exceeded the door-to-groin puncture time limit computed from the baseline period by about 10 min. None of the patients had a major complication following the procedures. None of the patients was or became SARS-CoV2 positive. In conclusion, we were able to manage the new hub-and-spoke system safely and without significant delays. The reshaping of the SU was made possible by the significant reduction of out-patient activity. The consequences of this reduction are still unknown but eventually, this emergency will suggest ways to reconsider the management and the allocation of health system resources.

Reversible Encephalopathy Syndrome (PRES) in a COVID-19 patient.

Recently WHO has declared novel coronavirus disease 2019 (COVID-19) outbreak a pandemic. Acute respiratory syndrome seems to be the most common manifestation of COVID-19. Besides pneumonia, it has been demonstrated that SARS-CoV-2 infection affects multiple organs, including brain tissues, causing different neurological manifestations, especially acute cerebrovascular disease (ischemic and hemorrhagic stroke), impaired consciousness and skeletal muscle injury. To our knowledge, among neurological disorders associated with SARS-CoV2 infection, no Posterior Reversible Encephalopathy Syndrome (PRES) has been described yet. Herein, we report a case of a 64-year old woman with COVID19 infection who developed a PRES, and we suggest that it could be explained by the disruption of the blood brain barrier induced by the cerebrovascular endothelial dysfunction caused by SARS-CoV-2.