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1.
J Neurol Sci ; 462: 123066, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38824818

ABSTRACT

BACKGROUND: Status epilepticus, characterized by the temporal neurological deficits, often mimics acute ischemic stroke. We investigated the usefulness of magnetic resonance imaging for differentiation of status epilepticus from acute ischemic stroke. METHODS: A retrospective case series of patients with status epilepticus who underwent brain magnetic resonance imaging. For comparative analysis, a series of patients with acute ischemic stroke caused by unilateral middle cerebral artery occlusion was used. RESULTS: Ten patients (4 females and 6 males) with status epilepticus who underwent brain magnetic resonance imaging were included. The median age at diagnosis was 82 years (age range, 70-90 years). In all ten patients, hyperintensities in diffusion-weighted imaging with decreased apparent diffusion coefficient values, decreased venous intensity in susceptibility-weighted imaging, and hyperperfusion in arterial spin labeling perfusion were detected in the cortex of the affected side. Four patients showed an additional diffusion restriction in the thalamus. The apparent diffusion coefficient value of the lesional area was 13.1% less than the contralateral, which was less than one-third as acute ischemic stroke. Status epilepticus patients showed no change in medullary venous intensity of the affected area in susceptibility-weighted imaging, whereas acute ischemic stroke patients showed increased cortical and medullary venous intensity in affected hemisphere. Seven of eight patients with status epilepticus who underwent magnetic resonance angiography showed dilation of the cerebral arteries in the ipsilateral side. CONCLUSIONS: The combined use of diffusion-weighted imaging, susceptibility-weighted imaging, and arterial spin labeling perfusion may help accurate and prompt diagnosis of status epilepticus.


Subject(s)
Ischemic Stroke , Magnetic Resonance Imaging , Status Epilepticus , Humans , Female , Male , Aged , Status Epilepticus/diagnostic imaging , Aged, 80 and over , Retrospective Studies , Magnetic Resonance Imaging/methods , Ischemic Stroke/diagnostic imaging , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging/methods , Brain Ischemia/diagnostic imaging , Stroke/diagnostic imaging
2.
Epilepsia ; 65(6): 1568-1580, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38606600

ABSTRACT

OBJECTIVE: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy. METHODS: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow-up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes. RESULTS: Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow-up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10-year follow-up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal-appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty-four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten-year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities. SIGNIFICANCE: Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status.


Subject(s)
Epilepsy, Temporal Lobe , Hippocampus , Magnetic Resonance Imaging , Sclerosis , Seizures, Febrile , Status Epilepticus , Humans , Hippocampus/pathology , Hippocampus/diagnostic imaging , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/pathology , Male , Female , Sclerosis/pathology , Status Epilepticus/diagnostic imaging , Status Epilepticus/pathology , Status Epilepticus/etiology , Seizures, Febrile/pathology , Seizures, Febrile/diagnostic imaging , Infant , Child, Preschool , Child , Follow-Up Studies , Atrophy/pathology , Hippocampal Sclerosis
3.
Epilepsia ; 65(6): 1620-1630, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38507291

ABSTRACT

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.


Subject(s)
Magnetic Resonance Imaging , Status Epilepticus , Humans , Status Epilepticus/diagnostic imaging , Case-Control Studies , Male , Female , Middle Aged , Adult , Magnetic Resonance Imaging/methods , Aged , Prospective Studies , Young Adult , Adolescent , Hippocampus/diagnostic imaging , Hippocampus/pathology , Brain/diagnostic imaging , Brain/pathology , Diffusion Magnetic Resonance Imaging , Child
4.
Neuropharmacology ; 251: 109918, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38527652

ABSTRACT

Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, there are limited data comparing the neuroprotective efficacy of diazepam versus midazolam following acute OP intoxication. To address this data gap, we used non-invasive imaging techniques to longitudinally quantify neuropathology in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) with and without post-exposure intervention with diazepam or midazolam. Magnetic resonance imaging (MRI) was used to monitor neuropathology and brain atrophy, while positron emission tomography (PET) with a radiotracer targeting translocator protein (TSPO) was utilized to assess neuroinflammation. Animals were scanned at 3, 7, 28, 65, 91, and 168 days post-DFP and imaging metrics were quantitated for the hippocampus, amygdala, piriform cortex, thalamus, cerebral cortex and lateral ventricles. In the DFP-intoxicated rat, neuroinflammation persisted for the duration of the study coincident with progressive atrophy and ongoing tissue remodeling. Benzodiazepines attenuated neuropathology in a region-dependent manner, but neither benzodiazepine was effective in attenuating long-term neuroinflammation as detected by TSPO PET. Diffusion MRI and TSPO PET metrics were highly correlated with seizure severity, and early MRI and PET metrics were positively correlated with long-term brain atrophy. Collectively, these results suggest that anti-seizure therapy alone is insufficient to prevent long-lasting neuroinflammation and tissue remodeling.


Subject(s)
Brain Injuries , Status Epilepticus , Rats , Animals , Diazepam/pharmacology , Midazolam/pharmacology , Midazolam/therapeutic use , Isoflurophate/pharmacology , Organophosphates , Neuroinflammatory Diseases , Neuroprotection , Rats, Sprague-Dawley , Brain/metabolism , Benzodiazepines/pharmacology , Status Epilepticus/chemically induced , Status Epilepticus/diagnostic imaging , Status Epilepticus/drug therapy , Positron-Emission Tomography , Carrier Proteins/metabolism , Magnetic Resonance Imaging , Brain Injuries/metabolism , Atrophy/pathology
5.
Epilepsy Res ; 202: 107343, 2024 May.
Article in English | MEDLINE | ID: mdl-38552593

ABSTRACT

BACKGROUND: Convulsive (CSE) and non-convulsive (NCSE) Status Epilepticus are a complication in 0.2-0.3% ischemic strokes. Large stroke and cortical involvement are the main risk factors for developing SE. This study evaluates the prevalence of SE in patients treated with endovascular thrombectomy (EVT) through EEG recording within 72- h from admission. Moreover, we compared clinical, radiological, and outcome measures in SE and no-SE patients. MATERIALS AND METHODS: We collected retrospectively demographical and clinical characteristics of acute ischemic stroke patients who underwent EVT, admitted in the Stroke Unit (SU) of the University Hospital of Trieste between January 2018 and March 2020 who underwent EEG recording within 72- h from the symptoms' onset. RESULTS: Out of 247 EVT patients, 138 met the inclusion criteria, of whom 9 (6.5%) showed SE with median onset time of 1 day (IQR 1-2). No difference was found between the two groups as for age, sex, risk factors, grade of recanalization, etiology of stroke, and closed vessel. The no-SE group presented higher NIHSS improvement rate (p=0.025) compared to the SE group. The sum of the lobes involved in the ischemic lesion was significantly higher in SE group (p=0.048). CONCLUSION: SE after EVT in large strokes is a non-rare complication, with most being NCSE. Performing a rapid EEG assessment in a Stroke Unit setting may allow for a prompt recognition and treatment of SE in the acute/hyper-acute phase. SE may be correlated with worse clinical outcomes in patients with large vessel occlusion.


Subject(s)
Electroencephalography , Status Epilepticus , Thrombectomy , Humans , Status Epilepticus/physiopathology , Status Epilepticus/diagnostic imaging , Electroencephalography/methods , Male , Female , Aged , Thrombectomy/methods , Retrospective Studies , Middle Aged , Prognosis , Ischemic Stroke/surgery , Ischemic Stroke/physiopathology , Ischemic Stroke/diagnostic imaging , Stroke/surgery , Stroke/physiopathology , Aged, 80 and over , Risk Factors , Brain Ischemia/physiopathology , Brain Ischemia/surgery
6.
J Neuroimaging ; 34(3): 393-401, 2024.
Article in English | MEDLINE | ID: mdl-38499979

ABSTRACT

BACKGROUND AND PURPOSE: We aimed to explore structural connectivity in status epilepticus. METHODS: We enrolled participants who underwent diffusion tensor imaging. We applied graph theory to investigate structural connectivity. We compared the structural connectivity measures between patients and healthy controls and between patients with poor (modified Rankin Scale [mRS] >3) and good (mRS ≤3) admission outcomes. RESULTS: We enrolled 28 patients and 31 healthy controls (age 65.5 vs.62.0 years, p = .438). Of these patients, 16 and 12 showed poor and good admission outcome (age 65.5 vs.62.0 years, p = .438). The assortative coefficient (-0.113 vs. -0.121, p = .021), mean clustering coefficient (0.007 vs.0.006, p = .009), global efficiency (0.023 vs.0.020, p = .009), transitivity (0.007 vs.0.006, p = .009), and small-worldness index (0.006 vs.0.005, p = .021) were higher in patients with status epilepticus than in healthy controls. The assortative coefficient (-0.108 vs. -0.119, p = .042), mean clustering coefficient (0.007 vs.0.006, p = .042), and transitivity (0.008 vs.0.007, p = .042) were higher in patients with poor admission outcome than in those with good admission outcome. MRS score was positively correlated with structural connectivity measures, including the assortative coefficient (r = 0.615, p = .003), mean clustering coefficient (r = 0.544, p = .005), global efficiency (r = 0.515, p = .007), transitivity (r = 0.547, p = .007), and small-worldness index (r = 0.435, p = .024). CONCLUSION: We revealed alterations in structural connectivity, showing increased integration and segregation in status epilepticus, which might be related with neuronal synchronization. This effect was more pronounced in patients with a poor admission outcome, potentially reshaping our understanding for comprehension of status epilepticus mechanisms and the development of more targeted treatments.


Subject(s)
Brain , Diffusion Tensor Imaging , Status Epilepticus , Humans , Status Epilepticus/diagnostic imaging , Status Epilepticus/physiopathology , Female , Male , Diffusion Tensor Imaging/methods , Middle Aged , Aged , Brain/diagnostic imaging , Prognosis , Nerve Net/diagnostic imaging , Nerve Net/physiopathology
7.
Sci Rep ; 14(1): 5063, 2024 03 01.
Article in English | MEDLINE | ID: mdl-38424459

ABSTRACT

The ketogenic diet (KD) has been shown to be effective in refractory epilepsy after long-term administration. However, its interference with short-term brain metabolism and its involvement in the early process leading to epilepsy remain poorly understood. This study aimed to assess the effect of a short-term ketogenic diet on cerebral glucose metabolic changes, before and after status epilepticus (SE) in rats, by using [18F]-FDG PET. Thirty-nine rats were subjected to a one-week KD (KD-rats, n = 24) or to a standard diet (SD-rats, n = 15) before the induction of a status epilepticus (SE) by lithium-pilocarpine administrations. Brain [18F]-FDG PET scans were performed before and 4 h after this induction. Morphological MRIs were acquired and used to spatially normalize the PET images which were then analyzed voxel-wisely using a statistical parametric-based method. Twenty-six rats were analyzed (KD-rats, n = 15; SD-rats, n = 11). The 7 days of the KD were associated with significant increases in the plasma ß-hydroxybutyrate level, but with an unchanged glycemia. The PET images, recorded after the KD and before SE induction, showed an increased metabolism within sites involved in the appetitive behaviors: hypothalamic areas and periaqueductal gray, whereas no area of decreased metabolism was observed. At the 4th hour following the SE induction, large metabolism increases were observed in the KD- and SD-rats in areas known to be involved in the epileptogenesis process late-i.e., the hippocampus, parahippocampic, thalamic and hypothalamic areas, the periaqueductal gray, and the limbic structures (and in the motor cortex for the KD-rats only). However, no statistically significant difference was observed when comparing SD and KD groups at the 4th hour following the SE induction. A one-week ketogenic diet does not prevent the status epilepticus (SE) and associated metabolic brain abnormalities in the lithium-pilocarpine rat model. Further explorations are needed to determine whether a significant prevention could be achieved by more prolonged ketogenic diets and by testing this diet in less severe experimental models, and moreover, to analyze the diet effects on the later and chronic stages leading to epileptogenesis.


Subject(s)
Diet, Ketogenic , Status Epilepticus , Rats , Animals , Pilocarpine/pharmacology , Lithium/pharmacology , Rats, Wistar , Fluorodeoxyglucose F18/pharmacology , Status Epilepticus/chemically induced , Status Epilepticus/diagnostic imaging , Brain/diagnostic imaging , Hippocampus , Disease Models, Animal
8.
J Neuroimmunol ; 388: 578298, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38330780

ABSTRACT

PURPOSE: New-Onset Refractory Status Epilepticus (NORSE) is a rare and severe form of refractory status epilepticus without an apparent underlying cause at presentation or prior history of epilepsy. We aimed to describe the clinical features, etiology, treatment, and outcomes of NORSE in adults in a quaternary-level hospital in Saudi Arabia. METHODOLOGY: In this retrospective cohort study, inclusion criteria involved patients over 14 years old who met the 2018 consensus definition for NORSE. Patients were identified using a combination of medical record admission labels 'status epilepticus' and 'encephalitis', and continuous EEG reports documenting status epilepticus. Demographic, clinical, and radiological data were collected and then analyzed for factors correlated with specific etiologies, better functional outcomes, and future diagnosis of epilepsy. RESULTS: We found 24 patients presenting with NORSE between 2010 and 2021. Fever/infectious symptoms were the most common prodrome. Elevated inflammatory serum and cerebrospinal fluid markers in most patients. Brain MRI revealed T2/FLAIR hyperintensity patterns, predominantly affecting limbic and perisylvian structures. The etiology of NORSE varied, with immune-related causes being the most common. Long-term outcomes were poor, with a high mortality rate and most survivors developing drug-resistant epilepsy. CONCLUSION: This study provides valuable insights into NORSE's clinical characteristics, highlighting the heterogeneity of this condition. The poor outcome is likely related to the progressive nature of the underlying disease, where refractory seizures are a clinical symptom. Thus, we propose to focus future research on the etiology rather than the NORSE acronym.


Subject(s)
Drug Resistant Epilepsy , Encephalitis , Status Epilepticus , Adult , Humans , Adolescent , Retrospective Studies , Status Epilepticus/diagnostic imaging , Status Epilepticus/drug therapy , Drug Resistant Epilepsy/diagnostic imaging , Encephalitis/complications , Magnetic Resonance Imaging
9.
Epilepsia Open ; 9(1): 258-267, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37943120

ABSTRACT

OBJECTIVE: Cardio-facio-cutaneous syndrome (CFC) is a genetic disorder due to variants affecting genes coding key proteins of the Ras/MAPK signaling pathway. Among the different features of CFC, neurological involvement, including cerebral malformations and epilepsy, represents a common and clinically relevant aspect. Status epilepticus (SE) is a recurrent feature, especially in a specific subgroup of CFC patients with developmental and epileptic encephalopathy (DEE) and history of severe pharmacoresistant epilepsy. Here we dissect the features of SE in CFC patients with a particular focus on longitudinal magnetic resonance imaging (MRI) findings to identify clinical-radiological patterns and discuss the underlying physiopathology. METHODS: We retrospectively analyzed clinical, electroencephalogram (EEG), and MRI data collected in a single center from a cohort of 23 patients with CFC carrying pathogenic BRAF variants who experienced SE during a 5-year period. RESULTS: Seven episodes of SE were documented in 5 CFC patients who underwent EEG and MRI at baseline. MRI was performed during SE/within 72 hours from SE termination in 5/7 events. Acute/early post-ictal MRI findings showed heterogenous abnormalities: restricted diffusion in 2/7, focal area of pcASL perfusion change in 2/7, focal cortical T2/FLAIR hyperintensity in 2/7. Follow-up images were available for 4/7 SE. No acute changes were detected in 2/7 (MRI performed 4 days after SE termination). SIGNIFICANCE: Acute focal neuroimaging changes concomitant with ictal EEG focus were present in 5/7 episodes, though with different findings. The heterogeneous patterns suggest different contributing factors, possibly including the presence of focal cortical malformations and autoinflammation. When cytotoxic edema is revealed by MRI, it can be followed by permanent structural damage, as already observed in other genetic conditions. A better understanding of the physiopathology will provide access to targeted treatments allowing to prevent long-term adverse neurological outcome. PLAIN LANGUAGE SUMMARY: Cardio-facio-cutaneous syndrome is a genetic disorder that often causes prolonged seizures known as status epilepticus. This study has a focus on electroclinical and neuroimaging patterns in patients with cardio-facio-cutaneous syndrome. During these status epilepticus episodes, we found different abnormal brain imaging patterns in patients, indicating various causes like brain malformations and inflammation. Understanding these patterns could help doctors find specific treatments, protecting cardio-facio-cutaneous syndrome patients from long-term brain damage.


Subject(s)
Ectodermal Dysplasia , Epilepsy , Facies , Failure to Thrive , Heart Defects, Congenital , Status Epilepticus , Humans , Proto-Oncogene Proteins B-raf/genetics , Retrospective Studies , Status Epilepticus/diagnostic imaging , Status Epilepticus/genetics , Neuroimaging
10.
J Neurol Neurosurg Psychiatry ; 95(5): 471-476, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38041670

ABSTRACT

BACKGROUND: Non-convulsive status epilepticus (NCSE) is a time-dependent neurological disorder often misdiagnosed in the emergency setting. Electroencephalography (EEG) is often not available on a 24/7 basis, and Salzburg criteria may at times miss the diagnosis. Here, we tested the accuracy of hyperperfusion on CT perfusion imaging (CTP) in the identification of NCSE against Salzburg criteria, to define its potential role in a pragmatic diagnostic workflow. METHODS: We enrolled consecutive patients with suspected acute seizure or seizure disorder undergoing brain imaging with CTP and EEG from January 2021 to March 2023. EEG recordings, Salzburg criteria and CTP hyperperfusion were rated and adjudicated by two independent experts blinded to patient status. A reference standard including all clinical, lab, imaging, EEG and therapeutic data was used to adjudicate NCSE diagnosis. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (NPV) were calculated for CTP hyperperfusion and Salzburg criteria versus NCSE adjudicated according to reference standard. RESULTS: Seventy-seven patients were enrolled. Among 21 NCSE cases, 17 were adjudicated according to Salzburg criteria (81%) and 4 received NCSE diagnosis according to reference standard. Agreement between EEG and CTP emerged in 16/21 NCSE cases, reaching sublobar level in 37.5% of cases. Receiver operator curve analysis suggested good accuracy for CTP hyperperfusion for the diagnosis of NCSE (AUROC 0.79, 95% CI 0.69 to 0.89). CTP hyperperfusion had a high NPV for NCSE (NPV 0.97, 95% CI 0.86 to 1). CONCLUSION: CTP hyperperfusion may be implemented in the emergency fast-track to rule out NCSE, given very high NPV. Further validation studies are needed to evaluate CTP application in real-world setting for NCSE codes.


Subject(s)
Status Epilepticus , Humans , Brain , Electroencephalography/methods , Perfusion , Status Epilepticus/diagnostic imaging , Prospective Studies
11.
Seizure ; 114: 106-110, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38118284

ABSTRACT

PURPOSE: This study was to correlate EEG patterns with peri­ictal perfusion CT abnormality (PCA) or peri­ictal MR abnormality (PMA) in patients with status epilepticus (SE). METHODS: This is a retrospective study done with SE patients from January 2016 to December 2021. We defined the PCA as single or multi-territorial cortical and/or thalamic hyper-perfusion. The PMA was defined as increased signal intensity in multiple brain regions including the cortex and subcortical regions. EEG patterns were categorized into electrographic seizure (ESz)/electroclinical seizure (ECSz), ictal-interictal continuum (IIC), and lateralized periodic discharges (LPDs) per the American Clinical Neurophysiology Society's guideline. We analyzed the association between the patterns of EEG and the presence of PCA or PMA. RESULTS: Among 73 patients, 26 % (19/73) showed PCA and 25 % (18/73) demonstrated PMA. The patterns of EEG were as follows; ESz/ECSz in 25 % (18/73), IIC in 34 % (25/73), and LPD in 12 % (9/73). There was a significant correlation between the patterns of EEG and the presence of PMA, but not PCA. 48 % (12/25) had both PMA and PCA whereas 52 % (13/25) showed either PMA (6/25) or PCA (7/25). CONCLUSION: Although PCA did not reveal an electro-radiographical correlation, PMA was strongly linked to ESz, ECSz, IIC, and LPD.


Subject(s)
Electroencephalography , Status Epilepticus , Humans , Retrospective Studies , Electroencephalography/methods , Status Epilepticus/diagnostic imaging , Seizures , Neuroimaging
12.
Epilepsy Behav ; 142: 109175, 2023 05.
Article in English | MEDLINE | ID: mdl-37003103

ABSTRACT

How status epilepticus (SE) is generated and propagates in the brain is not known. As for seizures, a patient-specific approach is necessary, and the analysis should be performed at the whole brain level. Personalized brain models can be used to study seizure genesis and propagation at the whole brain scale in The Virtual Brain (TVB), using the Epileptor mathematical construct. Building on the fact that SE is part of the repertoire of activities that the Epileptor can generate, we present the first attempt to model SE at the whole brain scale in TVB, using data from a patient who experienced SE during presurgical evaluation. Simulations reproduced the patterns found with SEEG recordings. We find that if, as expected, the pattern of SE propagation correlates with the properties of the patient's structural connectome, SE propagation also depends upon the global state of the network, i.e., that SE propagation is an emergent property. We conclude that individual brain virtualization can be used to study SE genesis and propagation. This type of theoretical approach may be used to design novel interventional approaches to stop SE. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.


Subject(s)
Connectome , Status Epilepticus , Humans , Status Epilepticus/diagnostic imaging , Seizures , Brain/diagnostic imaging , London
15.
Epilepsia ; 64(6): 1594-1604, 2023 06.
Article in English | MEDLINE | ID: mdl-36892496

ABSTRACT

OBJECTIVE: This study was undertaken to characterize the blood-brain barrier (BBB) dysfunction in patients with new onset refractory status epilepticus (NORSE) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: This study included three groups of adult participants: patients with NORSE, encephalitis patients without status epilepticus (SE), and healthy subjects. These participants were retrospectively included from a prospective DCE-MRI database of neurocritically ill patients and healthy subjects. The BBB permeability (Ktrans) in the hippocampus, basal ganglia, thalamus, claustrum, periventricular white matter, and cerebellum were measured and compared between these three groups. RESULTS: A total of seven patients with NORSE, 14 encephalitis patients without SE, and nine healthy subjects were included in this study. Among seven patients with NORSE, only one had a definite etiology (autoimmune encephalitis), and the rest were cryptogenic. Etiology of encephalitis patients without SE included viral (n = 2), bacterial (n = 8), tuberculous (n = 1), cryptococcal (n = 1), and cryptic (n = 2) encephalitis. Of these 14 encephalitis patients without SE, three patients had seizures. Compared to healthy controls, NORSE patients had significantly increased Ktrans values in the hippocampus (.73 vs. .02 × 10-3 /min, p = .001) and basal ganglia (.61 vs. .003 × 10-3 /min, p = .007) and a trend in the thalamus (.24 vs. .08 × 10-3 /min, p = .017). Compared to encephalitis patients without SE, NORSE patients had significantly increased Ktrans values in the thalamus (.24 vs. .01 × 10-3 /min, p = .002) and basal ganglia (.61 vs. .004 × 10-3 /min, p = .013). SIGNIFICANCE: This exploratory study demonstrates that BBBs of NORSE patients were impaired diffusely, and BBB dysfunction in the basal ganglia and thalamus plays an important role in the pathophysiology of NORSE.


Subject(s)
Encephalitis , Status Epilepticus , Adult , Humans , Blood-Brain Barrier/diagnostic imaging , Retrospective Studies , Prospective Studies , Status Epilepticus/diagnostic imaging , Status Epilepticus/etiology , Encephalitis/complications , Magnetic Resonance Imaging
16.
Epilepsy Behav ; 141: 109130, 2023 04.
Article in English | MEDLINE | ID: mdl-36803874

ABSTRACT

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.


Subject(s)
Neocortex , Status Epilepticus , Humans , Prospective Studies , Electroencephalography , Status Epilepticus/diagnostic imaging , Status Epilepticus/pathology , Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/methods , Neocortex/pathology , Spin Labels
17.
Brain Res ; 1803: 148227, 2023 03 15.
Article in English | MEDLINE | ID: mdl-36592802

ABSTRACT

BACKGROUND: Development of effective drugs for epilepsy are needed, as nearly 30 % of epileptic patients, are resistant to current treatments. This study is aimed to characterize the anticonvulsant effect of dapsone (DDS), in the kainic acid (KA)-induced Status Epilepticus (SE) by recording the brain metabolic activity with an [18F]FDG-PET analysis. METHODS: Wistar rats received KA (10 mg/kg, i.p., single dose) to produce sustained seizures. [18F]FDG-PET and electroencephalographic (EEG) studies were then performed. DDS or vehicle were administered 30 min before KA. [18F]FDG uptake and EEG were evaluated at baseline, 2 and 25 h after KA injection. Likewise, caspase-8, 3 hippocampal activities and Fluoro-Jade B neuronal degeneration and Hematoxylin-eosin staining were measured 25 h after KA. RESULTS: PET data evaluated at 2 h showed hyper-uptake of [18F]FDG in the control group, which was decreased by DDS. At 25 h, hypo-uptake was observed in the control group and higher values due to DDS effect. EEG spectral power was increased 2 h after KA administration in the control group during the generalized tonic-clonic seizures, which was reversed by DDS, correlated with [18F]FDG-PET uptake changes. The values of caspases-8 activity decreased 48 and 43 % vs control group in the groups treated with DDS (12.5 y 25 mg/kg respectively), likewise; caspase-3 activity diminished by 57 and 53 %. Fewer degenerated neurons were observed due to DDS treatments. CONCLUSIONS: This study pinpoints the anticonvulsant therapeutic potential of DDS. Given its safety and effectiveness, DDS may be a viable alternative for patients with drug-resistant epilepsy.


Subject(s)
Epilepsy , Status Epilepticus , Rats , Animals , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Kainic Acid/pharmacology , Fluorodeoxyglucose F18/metabolism , Dapsone/pharmacology , Rats, Wistar , Status Epilepticus/chemically induced , Status Epilepticus/diagnostic imaging , Status Epilepticus/drug therapy , Seizures/metabolism , Hippocampus/metabolism , Epilepsy/metabolism
18.
Epilepsia Open ; 8(2): 399-410, 2023 06.
Article in English | MEDLINE | ID: mdl-36718979

ABSTRACT

OBJECTIVE: Exposure to the nerve agent, soman (GD), induces status epilepticus (SE), epileptogenesis, and even death. Although rodent models studying the pathophysiological mechanisms show females to be more reactive to soman, no tangible sex differences in brains postexposure have been reported. In this study, we used multimodal imaging using MRI in adult rats to determine potential sex-based biomarkers of soman effects. METHODS: Male and female Sprague Dawley rats were challenged with 1.2 × LD50 soman followed by medical countermeasures. Ten weeks later, the brains were analyzed via structural and functional MRI. RESULTS: Despite no significant sex differences in the initial SE severity after soman exposure, long-term MRI-based structural and functional differences were evident in the brains of both sexes. While T2 MRI showed lesser soman-induced neurodegeneration, large areas of T1 enhancements occurred in females than in males, indicating a distinct pathophysiology unrelated to neurodegeneration. fMRI-based resting-state functional connectivity (RSFC), indicated greater reductions in soman-exposed females than in males, associating with the T1 enhancements (unrelated to neurodegeneration) rather than T2-hyperintensity or T1-hypointensity (representing neurodegeneration). The wider T1 enhancements associating with the decreased spontaneous neuronal activity in multiple resting-state networks in soman-exposed females than males suggest that neural changes unrelated to cellular atrophy impinge on brain function postexposure. Taken together with lower spontaneous neural activity in soman-exposed females, the results indicate some form of neuroprotective state that was not present in males. SIGNIFICANCE: The results indicate that endpoints other than neurodegeneration may need to be considered to translate sex-based nerve agent effects in humans.


Subject(s)
Nerve Agents , Soman , Status Epilepticus , Humans , Female , Rats , Male , Animals , Soman/toxicity , Nerve Agents/adverse effects , Rats, Sprague-Dawley , Status Epilepticus/chemically induced , Status Epilepticus/diagnostic imaging , Brain/diagnostic imaging , Magnetic Resonance Imaging
19.
Epilepsia ; 64(2): 511-523, 2023 02.
Article in English | MEDLINE | ID: mdl-36507708

ABSTRACT

OBJECTIVE: The P2X7 receptor (P2X7R) is an important contributor to neuroinflammation, responding to extracellularly released adenosine triphosphate. Expression of the P2X7R is increased in the brain in experimental and human epilepsy, and genetic or pharmacologic targeting of the receptor can reduce seizure frequency and severity in preclinical models. Experimentally induced seizures also increase levels of the P2X7R in blood. Here, we tested 18 F-JNJ-64413739, a positron emission tomography (PET) P2X7R antagonist, as a potential noninvasive biomarker of seizure-damage and epileptogenesis. METHODS: Status epilepticus was induced via an intra-amygdala microinjection of kainic acid. Static PET studies (30 min duration, initiated 30 min after tracer administration) were conducted 48 h after status epilepticus via an intravenous injection of 18 F-JNJ-64413739. PET images were coregistered with a brain magnetic resonance imaging atlas, tracer uptake was determined in the different brain regions and peripheral organs, and values were correlated to seizure severity during status epilepticus. 18 F-JNJ-64413739 was also applied to ex vivo human brain slices obtained following surgical resection for intractable temporal lobe epilepsy. RESULTS: P2X7R radiotracer uptake correlated strongly with seizure severity during status epilepticus in brain structures including the cerebellum and ipsi- and contralateral cortex, hippocampus, striatum, and thalamus. In addition, a correlation between radiotracer uptake and seizure severity was also evident in peripheral organs such as the heart and the liver. Finally, P2X7R radiotracer uptake was found elevated in brain sections from patients with temporal lobe epilepsy when compared to control. SIGNIFICANCE: Taken together, our data suggest that P2X7R-based PET imaging may help to identify seizure-induced neuropathology and temporal lobe epilepsy patients with increased P2X7R levels possibly benefitting from P2X7R-based treatments.


Subject(s)
Epilepsy, Temporal Lobe , Status Epilepticus , Mice , Humans , Male , Animals , Epilepsy, Temporal Lobe/metabolism , Receptors, Purinergic P2X7/metabolism , Receptors, Purinergic P2X7/therapeutic use , Brain/diagnostic imaging , Brain/metabolism , Status Epilepticus/chemically induced , Status Epilepticus/diagnostic imaging , Status Epilepticus/metabolism , Seizures/drug therapy
20.
Eur J Pharmacol ; 939: 175453, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36516936

ABSTRACT

Status epilepticus (SE) triggered by lithium-pilocarpine is a model of epileptogenesis widely used in rats, reproducing many of the pathological features of human temporal lobe epilepsy (TLE). After the SE, a silent period takes place that precedes the occurrence of recurrent spontaneous seizures. This latent stage is characterized by brain glucose hypometabolism and intense neuronal damage, especially at the hippocampus. Importantly, interictal hypometabolism in humans is a predictive marker of epileptogenesis, being correlated to the extent and severity of neuronal damage. Among the potential mechanisms underpinning glucose metabolism impairment and the subsequent brain damage, a reduction of cerebral blood flow has been proposed. Accordingly, our goal was to evaluate the potential beneficial effects of naftidrofuryl (25 mg/kg i.p., twice after the insult), a vasodilator drug currently used for circulatory insufficiency-related pathologies. Thus, we measured the effects of naftidrofuryl on the short-term brain hypometabolism and hippocampal damage induced by SE in rats. 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) neuroimaging along with various neurohistochemical assays aimed to assess brain damage were performed. SE led to both severe glucose hypometabolism in key epilepsy-related areas and hippocampal neuronal damage. Although naftidrofuryl showed no anticonvulsant properties, it ameliorated the short-term brain hypometabolism induced by pilocarpine. Strikingly, the latter was neither accompanied by neuroprotective nor by anti-inflammatory effects. We suggest that naftidrofuryl, by acutely enhancing brain blood flow around the time of SE improves the brain metabolic state but this effect is not enough to protect from the damage induced by SE.


Subject(s)
Nafronyl , Status Epilepticus , Humans , Rats , Animals , Pilocarpine/pharmacology , Lithium/pharmacology , Nafronyl/metabolism , Nafronyl/pharmacology , Vasodilator Agents/pharmacology , Neuroprotection , Glucose/metabolism , Disease Models, Animal , Brain , Status Epilepticus/chemically induced , Status Epilepticus/diagnostic imaging , Status Epilepticus/drug therapy , Hippocampus , Seizures/metabolism
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