607 results on '"SEIZURES (Medicine)"'
Search Results
2. The interictal suppression hypothesis is the dominant differentiator of seizure onset zones in focal epilepsy.
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Doss, Derek J, Shless, Jared S, Bick, Sarah K, Makhoul, Ghassan S, Negi, Aarushi S, Bibro, Camden E, Rashingkar, Rohan, Gummadavelli, Abhijeet, Chang, Catie, Gallagher, Martin J, Naftel, Robert P, Reddy, Shilpa B, Roberson, Shawniqua Williams, Morgan, Victoria L, Johnson, Graham W, and Englot, Dario J
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SEIZURES (Medicine) , *PARTIAL epilepsy , *PRINCIPAL components analysis , *ACADEMIC medical centers , *PEOPLE with epilepsy - Abstract
Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the interictal suppression hypothesis posit that when the patient is not having a seizure, SOZs are inhibited by non-SOZs through high inward connectivity and low outward connectivity. However, it is not clear whether there are other motifs that can better identify potential SOZs. Thus, we sought to use unsupervised machine learning to identify network motifs that elucidate SOZs and investigate if there is another motif that outperforms the ISH. Resting-state SEEG data from 81 patients with drug-resistant epilepsy undergoing a pre-surgical evaluation at Vanderbilt University Medical Center were collected. Directed connectivity matrices were computed using the alpha band (8–13 Hz). Principal component analysis (PCA) was performed on each patient's connectivity matrix. Each patient's components were analysed qualitatively to identify common patterns across patients. A quantitative definition was then used to identify the component that most closely matched the observed pattern in each patient. A motif characteristic of the interictal suppression hypothesis (high-inward and low-outward connectivity) was present in all individuals and found to be the most robust motif for identification of SOZs in 64/81 (79%) patients. This principal component demonstrated significant differences in SOZs compared to non-SOZs. While other motifs for identifying SOZs were present in other patients, they differed for each patient, suggesting that seizure networks are patient specific, but the ISH is present in nearly all networks. We discovered that a potentially suppressive motif based on the interictal suppression hypothesis was present in all patients, and it was the most robust motif for SOZs in 79% of patients. Each patient had additional motifs that further characterized SOZs, but these motifs were not common across all patients. This work has the potential to augment clinical identification of SOZs to improve epilepsy treatment. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Threshold of somatic mosaicism leading to brain dysfunction with focal epilepsy.
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Kim, Jintae, Park, Sang Min, Koh, Hyun Yong, Ko, Ara, Kang, Hoon-Chul, Chang, Won Seok, Kim, Dong Seok, and Lee, Jeong Ho
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FOCAL cortical dysplasia , *CHILDHOOD epilepsy , *SOMATIC mutation , *SEIZURES (Medicine) , *MOSAICISM - Abstract
Somatic mosaicism in a fraction of brain cells causes neurodevelopmental disorders, including childhood intractable epilepsy. However, the threshold for somatic mosaicism leading to brain dysfunction is unknown. In this study, we induced various mosaic burdens in focal cortical dysplasia type II (FCD II) mice, featuring mTOR somatic mosaicism and spontaneous behavioural seizures. The mosaic burdens ranged from approximately 1000 to 40 000 neurons expressing the mTOR mutant in the somatosensory or medial prefrontal cortex. Surprisingly, approximately 8000–9000 neurons expressing the MTOR mutant, extrapolated to constitute 0.08%–0.09% of total cells or roughly 0.04% of variant allele frequency in the mouse hemicortex, were sufficient to trigger epileptic seizures. The mutational burden was correlated with seizure frequency and onset, with a higher tendency for electrographic inter-ictal spikes and beta- and gamma-frequency oscillations in FCD II mice exceeding the threshold. Moreover, mutation-negative FCD II patients in deep sequencing of their bulky brain tissues revealed somatic mosaicism of the mTOR pathway genes as low as 0.07% in resected brain tissues through ultra-deep targeted sequencing (up to 20 million reads). Thus, our study suggests that extremely low levels of somatic mosaicism can contribute to brain dysfunction. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Peripherally-derived LGI1-reactive monoclonal antibodies cause epileptic seizures in vivo.
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Upadhya, Manoj, Kirmann, Toni, Wilson, Max A, Simon, Christian M, Dhangar, Divya, Geis, Christian, Williams, Robyn, Woodhall, Gavin, Hallermann, Stefan, Irani, Sarosh R, and Wright, Sukhvir K
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EPILEPSY , *SEIZURES (Medicine) , *LABORATORY rats , *B cells , *MEMORY testing - Abstract
One striking clinical hallmark in patients with autoantibodies to leucine-rich glioma inactivated 1 (LGI1) is the very frequent focal seizure semiologies, including faciobrachial dystonic seizures (FBDS), in addition to the amnesia. Polyclonal serum IgGs have successfully modelled the cognitive changes in vivo but not seizures. Hence, it remains unclear whether LGI1-autoantibodies are sufficient to cause seizures. We tested this with the molecularly precise monoclonal antibodies directed against LGI1 [LGI1-monoclonal antibodies (mAbs)], derived from patient circulating B cells. These were directed towards both major domains of LGI1, leucine-rich repeat and epitempin repeat, and infused intracerebroventricularly over 7 days into juvenile male Wistar rats using osmotic pumps. Continuous wireless EEG was recorded from a depth electrode placed in hippocampal CA3 plus behavioural tests for memory and hyperexcitability were performed. Following infusion completion (Day 9), post-mortem brain slices were studied for antibody binding and effects on Kv1.1. The LGI1-mAbs bound most strongly in the hippocampal CA3 region and induced a significant reduction in Kv1.1 cluster number in this subfield. By comparison to control-Ab injected rats video-EEG analysis over 9 days revealed convulsive and non-convulsive seizure activity in rats infused with LGI1-mAbs, with a significant number of ictal events. Memory was not impaired in the novel object recognition test. Peripherally-derived human LGI1-mAbs infused into rodent CSF provide strong evidence of direct in vivo epileptogenesis with molecular correlations. These findings fulfill criteria for LGI1-antibodies in seizure causation. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Patterns of gabapentin prescription and of hospitalization in a national cohort of US Veterans.
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Levy, Deborah R, Gordon, Kirsha S, Bastian, Lori A, Brandt, Cynthia, and Gunderson, Craig
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AMERICAN veterans , *T-test (Statistics) , *HOSPITAL care , *DIZZINESS , *SEX distribution , *KRUSKAL-Wallis Test , *LOGISTIC regression analysis , *TREATMENT effectiveness , *RETROSPECTIVE studies , *DESCRIPTIVE statistics , *AGE distribution , *CHI-squared test , *LONGITUDINAL method , *DRUG approval , *RACE , *ODDS ratio , *PHYSICIAN practice patterns , *GABAPENTIN , *SEIZURES (Medicine) , *MEDICAL records , *ACQUISITION of data , *DRUG prescribing , *DRUGS , *POSTHERPETIC neuralgia , *DATA analysis software , *CONFIDENCE intervals , *ACCIDENTAL falls , *COMORBIDITY , *NOSOLOGY - Abstract
The article examines the relationship between gabapentin prescriptions and hospitalization rates among U.S. veterans, revealing that gabapentin use is associated with increased odds of hospitalization, regardless of dose. Topics discussed include the patterns of gabapentin prescriptions, the demographic and clinical characteristics of patients prescribed gabapentin, and the potential impact of gabapentin on hospitalization across different age groups.
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- 2024
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6. Knockdown of NeuroD2 leads to seizure-like behavior, brain neuronal hyperactivity and a leaky blood-brain barrier in a Xenopus laevis tadpole model of DEE75.
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Banerjee, Sulagna, Szyszka, Paul, and Beck, Caroline W
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BIOLOGICAL models , *RESEARCH funding , *BLOOD-brain barrier , *NEURONS , *BRAIN diseases , *SEIZURES (Medicine) , *ANIMAL experimentation , *EPILEPSY , *GENETIC techniques , *GENETIC mutation , *VERTEBRATES , *DNA-binding proteins , *PHENOTYPES , *GENETIC testing , *TRANSFORMING growth factors-beta ,BRAIN metabolism - Abstract
Developmental and Epileptic Encephalopathies (DEE) are a genetically diverse group of severe, early onset seizure disorders. DEE are normally identified clinically in the first six months of life by the presence of frequent, difficult to control seizures and accompanying stalling or regression of development. DEE75 results from de novo mutations of the NEUROD2 gene that result in loss of activity of the encoded transcription factor, and the seizure phenotype was shown to be recapitulated in Xenopus tropicalis tadpoles. We used CRISPR/Cas9 to make a DEE75 model in Xenopus laevis , to further investigate the developmental etiology. NeuroD2.S CRISPR/Cas9 edited tadpoles were more active, swam faster on average, and had more seizures (C-shaped contractions resembling unprovoked C-start escape responses) than their sibling controls. Live imaging of Ca2+ signaling revealed prolongued, strong signals sweeping through the brain, indicative of neuronal hyperactivity. While the resulting tadpole brain appeared grossly normal, the blood-brain barrier (BBB) was found to be leakier than that of controls. Additionally, the TGFβ antagonist Losartan was shown to have a short-term protective effect, reducing neuronal hyperactivity and reducing permeability of the BBB. Treatment of NeuroD2 CRISPant tadpoles with 5 mM Losartan decreased seizure events by more than 4-fold compared to the baseline. Our results support a model of DEE75 resulting from reduced NeuroD2 activity during vertebrate brain development, and indicate that a leaky BBB contributes to epileptogenesis. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Comparison of patients with biopsy positive and negative primary angiitis of the central nervous system.
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Nehme, Ahmad, Arquizan, Caroline, Régent, Alexis, Isabel, Clothilde, Dequatre, Nelly, Guillon, Benoît, Capron, Jean, Detante, Olivier, Lanthier, Sylvain, Poppe, Alexandre Y, Boulouis, Grégoire, Godard, Sophie, Terrier, Benjamin, Pagnoux, Christian, Aouba, Achille, Touzé, Emmanuel, Boysson, Hubert de, and Group, the Cohort of Patients with PACNS Study
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VASCULITIS , *BIOPSY , *STATISTICAL models , *RESEARCH funding , *T-test (Statistics) , *DIAGNOSTIC imaging , *LOGISTIC regression analysis , *FISHER exact test , *COMPUTED tomography , *SEX distribution , *STENOSIS , *SYMPTOMS , *RETROSPECTIVE studies , *DESCRIPTIVE statistics , *MULTIVARIATE analysis , *CHI-squared test , *MANN Whitney U Test , *ODDS ratio , *RESEARCH , *COGNITION disorders , *STATISTICS , *MAGNETIC resonance angiography , *SEIZURES (Medicine) , *CENTRAL nervous system diseases , *CONFIDENCE intervals , *CEREBRAL infarction , *DATA analysis software , *CEREBRAL hemorrhage - Abstract
Objective There is limited evidence on when to obtain a central nervous system (CNS) biopsy in suspected primary angiitis of the central nervous system (PACNS). Our objective was to identify which clinical and radiological characteristics were associated with a positive biopsy in PACNS. Methods From the multicentre retrospective Cohort of Patients with Primary Vasculitis of the CNS (COVAC), we included adults with PACNS based on a positive CNS biopsy or otherwise unexplained intracranial stenoses with additional findings supportive of vasculitis. Baseline findings were compared between patients with a positive and negative biopsy using logistic regression models. Results Two hundred patients with PACNS were included, among which a biopsy was obtained in 100 (50%) and was positive in 61 (31%). Patients with a positive biopsy were more frequently female (odds ratio [OR] 2.90; 95% CI: 1.25, 7.10; P = 0.01) and more often presented with seizures (OR 8.31; 95% CI: 2.77, 33.04; P < 0.001) or cognitive impairment (OR 2.58; 95% CI: 1.11, 6.10; P = 0.03). On imaging, biopsy positive patients more often had non-ischaemic parenchymal or leptomeningeal gadolinium enhancement (OR 52.80; 95% CI: 15.72, 233.06; P < 0.001) or ≥1 cerebral microbleed (OR 8.08; 95% CI: 3.03, 25.13; P < 0.001), and less often had ≥1 acute brain infarct (OR 0.02; 95% CI: 0.004, 0.08; P < 0.001). In the multivariable model, non-ischaemic parenchymal or leptomeningeal gadolinium enhancement (adjusted OR 8.27; 95% CI: 1.78, 38.46; P < 0.01) and absence of ≥1 acute brain infarct (adjusted OR 0.13; 95% CI: 0.03, 0.65; P = 0.01) were significantly associated with a positive biopsy. Conclusion Baseline clinical and radiological characteristics differed between biopsy positive and negative PACNS. These results may help physicians individualize the decision to obtain a CNS biopsy in suspected PACNS. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Development of a machine learning model and nomogram to predict seizures in children with COVID-19: a two-center study.
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Liu, Yu-Qi, Yuan, Wei-Hua, Tao, Yue, Zhao, Lian, and Guo, Wan-Liang
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MACHINE learning , *NOMOGRAPHY (Mathematics) , *RECEIVER operating characteristic curves , *SEIZURES (Medicine) , *COVID-19 , *JUVENILE diseases - Abstract
Objective This study aimed to use machine learning to evaluate the risk factors of seizures and develop a model and nomogram to predict seizures in children with coronavirus disease 2019 (COVID-19). Material and methods A total of 519 children with COVID-19 were assessed to develop predictive models using machine learning algorithms, including extreme gradient boosting (XGBoost), random forest (RF) and logistic regression (LR). The performance of the models was assessed using area under the receiver operating characteristic curve (AUC) values. Importance matrix plot and SHapley Additive exPlanations (SHAP) values were calculated to evaluate feature importance and to show the visualization results. The nomogram and clinical impact curve were used to validate the final model. Results Two hundred and seventeen children with COVID-19 had seizures. According to the AUC, the RF model performed the best. Based on the SHAP values, the top three most important variables in the RF model were neutrophil percentage, cough and fever duration. The nomogram and clinical impact curve also verified that the RF model possessed significant predictive value. Conclusions Our research indicates that the RF model demonstrates excellent performance in predicting seizures, and our novel nomogram can facilitate clinical decision-making and potentially offer benefit for clinicians to prevent and treat seizures in children with COVID-19. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Familial hemiplegic migraine in Indian children—a tertiary center experience.
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Saini, Lokesh, Gunasekaran, Pradeep Kumar, Tiwari, Sarbesh, Choudhary, Bharat, Manjunathan, Sujatha, and Kumar, Ashna
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MIGRAINE aura , *SUMATRIPTAN , *SCOTOMA , *SEIZURES (Medicine) , *CEREBRAL hemispheres , *GENETIC testing , *PERIMETRY - Abstract
Familial hemiplegic migraine (FHM), an autosomal dominant subtype of hemiplegic migraine, is a channelopathy presenting with severe headache, visual field defect, paresthesia, unilateral motor deficit, encephalopathy, seizures and aphasia. This cross-sectional study was conducted over 10 months in children aged 1–18 years suspected of hemiplegic migraine at a tertiary care pediatric hospital. Fourteen children were screened and five children with genetically confirmed FHM were included. The symptoms in the study population were paroxysmal hemiparesis (5/5), headache (5/5) and focal seizures (1/5). The hemiplegia episodes lasted from 4 h to 7 days. The mean age at the onset of neurological symptoms was 6.8 ± 0.7 years and the mean age at diagnosis was 12.8 ± 1.7 years, with a mean delay of 6.1 ± 1.9 years for the diagnosis. Neuroimaging during acute episodes revealed accentuated gray, white differentiation in the contralateral cerebral hemisphere with mild effacement of sulcal spaces in T2/fluid-attenuated inversion recovery (FLAIR) images. Genetic testing revealed ATP1A2 mutations (FHM2) in 4/5 and SCN1A (FHM3) in 1/5 patients. All of them (5/5) were initiated on oral topiramate and had favorable treatment responses with a mean follow-up duration of 7 ± 1.4 months. Diagnosis of FHM is mainly clinical and can be confirmed by genetic analysis. Perfusion and diffusion-weighted MRI should be considered during acute headache episodes, as it is mostly normal in symptom-free periods. Routine MRI sequences like T1 weighted, T2 weighted, FLAIR and contrast remain normal even during acute attacks. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer's disease and 5XFAD mice.
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Barbour, Aaron J, Gourmaud, Sarah, Lancaster, Eunjoo, Li, Xiaofan, Stewart, David A, Hoag, Keegan F, Irwin, David J, Talos, Delia M, and Jensen, Frances E
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ALZHEIMER'S disease , *RAPAMYCIN , *SEIZURES (Medicine) , *AMPA receptors , *GLUTAMATE receptors , *ANTICONVULSANTS , *EPILEPTIFORM discharges - Abstract
Approximately 22% of Alzheimer's disease (AD) patients suffer from seizures, and the co-occurrence of seizures and epileptiform activity exacerbates AD pathology and related cognitive deficits, suggesting that seizures may be a targetable component of AD progression. Given that alterations in neuronal excitatory:inhibitory (E:I) balance occur in epilepsy, we hypothesized that decreased markers of inhibition relative to those of excitation would be present in AD patients. We similarly hypothesized that in 5XFAD mice, the E:I imbalance would progress from an early stage (prodromal) to later symptomatic stages and be further exacerbated by pentylenetetrazol (PTZ) kindling. Post-mortem AD temporal cortical tissues from patients with or without seizure history were examined for changes in several markers of E:I balance, including levels of the inhibitory GABAA receptor, the sodium potassium chloride cotransporter 1 (NKCC1) and potassium chloride cotransporter 2 (KCC2) and the excitatory NMDA and AMPA type glutamate receptors. We performed patch-clamp electrophysiological recordings from CA1 neurons in hippocampal slices and examined the same markers of E:I balance in prodromal 5XFAD mice. We next examined 5XFAD mice at chronic stages, after PTZ or control protocols, and in response to chronic mTORC1 inhibitor rapamycin, administered following kindled seizures, for markers of E:I balance. We found that AD patients with comorbid seizures had worsened cognitive and functional scores and decreased GABAA receptor subunit expression, as well as increased NKCC1/KCC2 ratios, indicative of depolarizing GABA responses. Patch clamp recordings of prodromal 5XFAD CA1 neurons showed increased intrinsic excitability, along with decreased GABAergic inhibitory transmission and altered glutamatergic neurotransmission, indicating that E:I imbalance may occur in early disease stages. Furthermore, seizure induction in prodromal 5XFAD mice led to later dysregulation of NKCC1/KCC2 and a reduction in GluA2 AMPA glutamate receptor subunit expression, indicative of depolarizing GABA receptors and calcium permeable AMPA receptors. Finally, we found that chronic treatment with the mTORC1 inhibitor, rapamycin, at doses we have previously shown to attenuate seizure-induced amyloid-β pathology and cognitive deficits, could also reverse elevations of the NKCC1/KCC2 ratio in these mice. Our data demonstrate novel mechanisms of interaction between AD and epilepsy and indicate that targeting E:I balance, potentially with US Food and Drug Administration-approved mTOR inhibitors, hold therapeutic promise for AD patients with a seizure history. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Focal Seizures in a Patient With Chronic Basal Ganglia Calcifications Secondary to Idiopathic Primary Hypoparathyroidism.
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Zhang, Jennifer, Van, Karen, Carney, Patrick, Gilfillan, Christopher, and Grossmann, Mathis
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HYPOPARATHYROIDISM , *IDIOPATHIC diseases , *BASAL ganglia , *SEIZURES (Medicine) , *CALCIFICATION , *CONSCIOUSNESS raising - Abstract
Patients with hypoparathyroidism can present with concurrent basal ganglia calcifications (BGCs). The exact pathogenesis is unknown, although it is thought to relate to calcium-phosphate deposition from chronic hypocalcemia and hyperphosphatemia. We present the case of a 65-year-old man with known idiopathic primary hypoparathyroidism and concurrent extensive BGC. Thirty years after diagnosis, he presented with focal seizures despite a decade of stable intracranial calcifications on imaging. Serum calcium, phosphate, 25-hydroxyvitamin D, and parathyroid hormone levels were well controlled during this period. He was commenced on lifelong levetiracetam with subsequent seizure remission. Given the scarcity of literature surrounding focal seizures and BGC, it is essential to raise awareness in this area. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Increased expression of chondroitin sulfate proteoglycans in dentate gyrus and amygdala causes postinfectious seizures.
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Patel, Dipan C, Swift, Nathaniel, Tewari, Bhanu P, Browning, Jack L, Prim, Courtney, Chaunsali, Lata, Kimbrough, Ian F, Olsen, Michelle L, and Sontheimer, Harald
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DENTATE gyrus , *CHONDROITIN sulfates , *GRANULE cells , *AMYGDALOID body , *SEIZURES (Medicine) , *CHONDROITIN sulfate proteoglycan , *PROTEOGLYCANS - Abstract
Alterations in the extracellular matrix are common in patients with epilepsy and animal models of epilepsy, yet whether they are the cause or consequence of seizures and epilepsy development is unknown. Using Theiler's murine encephalomyelitis virus (TMEV) infection-induced model of acquired epilepsy, we found de novo expression of chondroitin sulfate proteoglycans (CSPGs), a major extracellular matrix component, in dentate gyrus (DG) and amygdala exclusively in mice with acute seizures. Preventing the synthesis of CSPGs specifically in DG and amygdala by deletion of the major CSPG aggrecan reduced seizure burden. Patch-clamp recordings from dentate granule cells revealed enhanced intrinsic and synaptic excitability in seizing mice that was significantly ameliorated by aggrecan deletion. In situ experiments suggested that dentate granule cell hyperexcitability results from negatively charged CSPGs increasing stationary cations on the membrane, thereby depolarizing neurons, increasing their intrinsic and synaptic excitability. These results show increased expression of CSPGs in the DG and amygdala as one of the causal factors for TMEV-induced acute seizures. We also show identical changes in CSPGs in pilocarpine-induced epilepsy, suggesting that enhanced CSPGs in the DG and amygdala may be a common ictogenic factor and potential therapeutic target. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Syncope or seizure: that is the question—case report of a young patient with convulsive cardioinhibitory syncope treated with cardioneuroablation.
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Papa, Andrea, Fisch, Urs, Bassetti, Stefano, Badertscher, Patrick, and Krisai, Philipp
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EPILEPSY ,SYNCOPE ,SEIZURES (Medicine) ,LOSS of consciousness ,ASYMPTOMATIC patients ,DIFFERENTIAL diagnosis ,CARDIAC arrest - Abstract
Background Differentiation of syncope from seizure is challenging and has therapeutic implications. Cardioinhibitory reflex syncope typically affects young patients where permanent pacing should be avoided whenever possible. Cardioneuroablation may obviate the need for a pacemaker in well-selected patients. Case summary A previously healthy 24-year-old woman was referred to the emergency department after recurrent episodes of transient loss of consciousness (TLOC). The electrocardiogram (ECG) and the echocardiogram were normal. An electroencephalogram (EEG) showed intermittent, generalized pathological activity. During EEG under photostimulation, the patient developed a short-term TLOC followed by brachial myocloni, while the concurrent ECG registered a progressive bradycardia, which turned into a complete atrioventricular block and sinus arrest with asystole for 14 s. Immediately after, the patient regained consciousness without sequelae. The episode was interpreted as cardioinhibitory convulsive syncope. However, due to the pathological EEG findings, an underlying epilepsy with ictal asystole could not be fully excluded. Therefore, an antiseizure therapy was also started. After discussing the consequences of pacemaker implantation, the patient agreed to undergo a cardioneuroablation and after 72 h without complications, she was discharged home. At 10 months, the patient autonomously discontinued the antiepileptics. The follow-up EEG displayed unspecific activities without clinical correlations. An implantable loop recorder didn't show any relevant bradyarrhythmia. At 1-year follow-up, the patient remained asymptomatic and without syncopal episodes. Discussion Reflex syncope must be considered in the differential diagnosis of seizures. The cardioneuroablation obviated the need for a pacemaker and allowed for the withdrawal of anticonvulsants, originally started on the premise of seizure. [ABSTRACT FROM AUTHOR]
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- 2024
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14. The clinical, imaging, pathological and genetic landscape of bottom-of-sulcus dysplasia.
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Macdonald-Laurs, Emma, Warren, Aaron E L, Francis, Peter, Mandelstam, Simone A, Lee, Wei Shern, Coleman, Matthew, Stephenson, Sarah E M, Barton, Sarah, D'Arcy, Colleen, Lockhart, Paul J, Leventer, Richard J, and Harvey, A Simon
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EPILEPSY , *TEMPORAL lobectomy , *VOXEL-based morphometry , *PARTIAL epilepsy , *DYSPLASIA , *FOCAL cortical dysplasia , *SODIUM channels , *SEIZURES (Medicine) - Abstract
Bottom-of-sulcus dysplasia (BOSD) is increasingly recognized as a cause of drug-resistant, surgically-remediable, focal epilepsy, often in seemingly MRI-negative patients. We describe the clinical manifestations, morphological features, localization patterns and genetics of BOSD, with the aims of improving management and understanding pathogenesis. We studied 85 patients with BOSD diagnosed between 2005–2022. Presenting seizure and EEG characteristics, clinical course, genetic findings and treatment response were obtained from medical records. MRI (3 T) and 18F-FDG-PET scans were reviewed systematically for BOSD morphology and metabolism. Histopathological analysis and tissue genetic testing were performed in 64 operated patients. BOSD locations were transposed to common imaging space to study anatomical location, functional network localization and relationship to normal MTOR gene expression. All patients presented with stereotyped focal seizures with rapidly escalating frequency, prompting hospitalization in 48%. Despite 42% patients having seizure remissions, usually with sodium channel blocking medications, most eventually became drug-resistant and underwent surgery (86% seizure-free). Prior developmental delay was uncommon but intellectual, language and executive dysfunction were present in 24%, 48% and 29% when assessed preoperatively, low intellect being associated with greater epilepsy duration. BOSDs were missed on initial MRI in 68%, being ultimately recognized following repeat MRI, 18F-FDG-PET or image postprocessing. MRI features were grey-white junction blurring (100%), cortical thickening (91%), transmantle band (62%), increased cortical T1 signal (46%) and increased subcortical FLAIR signal (26%). BOSD hypometabolism was present on 18F-FDG-PET in 99%. Additional areas of cortical malformation or grey matter heterotopia were present in eight patients. BOSDs predominated in frontal and pericentral cortex and related functional networks, mostly sparing temporal and occipital cortex, and limbic and visual networks. Genetic testing yielded pathogenic mTOR pathway variants in 63% patients, including somatic MTOR variants in 47% operated patients and germline DEPDC5 or NPRL3 variants in 73% patients with familial focal epilepsy. BOSDs tended to occur in regions where the healthy brain normally shows lower MTOR expression, suggesting these regions may be more vulnerable to upregulation of MTOR activity. Consistent with the existing literature, these results highlight (i) clinical features raising suspicion of BOSD; (ii) the role of somatic and germline mTOR pathway variants in patients with sporadic and familial focal epilepsy associated with BOSD; and (iii) the role of 18F-FDG-PET alongside high-field MRI in detecting subtle BOSD. The anatomical and functional distribution of BOSDs likely explain their seizure, EEG and cognitive manifestations and may relate to relative MTOR expression. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Ongoing Measles in the Developed and Developing World.
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Cherry, James D
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MEASLES complications , *PREVENTION of epidemics , *DIARRHEA , *OTITIS media , *PNEUMONIA , *ATTITUDES toward illness , *DEATH , *MEASLES , *SUBACUTE sclerosing panencephalitis , *PUBLIC opinion , *ENCEPHALITIS , *SEIZURES (Medicine) , *AMNESIA , *MEASLES vaccines ,DEVELOPED countries ,DEVELOPING countries - Abstract
Measles is a vaccine-preventable illness. Nevertheless, in recent years, measles is still endemic and epidemic in both the developed world and the developing world. The public perception of measles in the past was that it was not a big deal. However, measles is associated with a number of complications which can be places in three categories which are: acute(diarrhea, otitis media, pneumonia, encephalitis, seizures, and death) and delayed-subacute sclerosing panencephalitis (SSPE) and post-measles immune amnesia. Contrary to the beliefs of the anti-vaccine lobby, measles is bad. In acute measles, the death rate is 1–3 per 1000 and the risk of encephalitis is 1 per 1000. Relatively recent investigations indicate that SSPE is considerably more common than previously believed. The worldwide contribution of post-measles immune amnesia to morbidity and mortality is likely to be huge. In exposure situations, two doses of measles vaccine will prevent 99% of cases. Presently in the United States, the first dose is given at 12 through 15 months of age. The second dose is most often administered at 4 through 6 years of age. In my opinion, the second dose of measles vaccine should be given 4–6 weeks after the first dose rather than at 4–6 years of age. Children who don't have antibody to measles should not travel to risk areas. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Extracellular glutamate and GABA transients at the transition from interictal spiking to seizures.
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Shimoda, Yoshiteru, Leite, Marco, Graham, Robert T, Marvin, Jonathan S, Hasseman, Jeremy, Kolb, Ilya, Looger, Loren L, Magloire, Vincent, and Kullmann, Dimitri M
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GLUTAMIC acid , *GABA , *SEIZURES (Medicine) , *PROGRESSIVE collapse , *PARTIAL epilepsy - Abstract
Focal epilepsy is associated with intermittent brief population discharges (interictal spikes), which resemble sentinel spikes that often occur at the onset of seizures. Why interictal spikes self-terminate whilst seizures persist and propagate is incompletely understood. We used fluorescent glutamate and GABA sensors in an awake rodent model of neocortical seizures to resolve the spatiotemporal evolution of both neurotransmitters in the extracellular space. Interictal spikes were accompanied by brief glutamate transients which were maximal at the initiation site and rapidly propagated centrifugally. GABA transients lasted longer than glutamate transients and were maximal ∼1.5 mm from the focus where they propagated centripetally. Prior to seizure initiation GABA transients were attenuated, whilst glutamate transients increased, consistent with a progressive failure of local inhibitory restraint. As seizures increased in frequency, there was a gradual increase in the spatial extent of spike-associated glutamate transients associated with interictal spikes. Neurotransmitter imaging thus reveals a progressive collapse of an annulus of feed-forward GABA release, allowing seizures to escape from local inhibitory restraint. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Baclofen in the treatment of alcohol use disorder: tailored doses matter.
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Beaurepaire, Renaud de and Jaury, Philippe
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SUBSTANCE abuse , *BACLOFEN , *PATIENT education , *PATIENT safety , *TREATMENT effectiveness , *ANXIETY , *AFFECTIVE disorders , *PHYSICIAN practice patterns , *SEIZURES (Medicine) , *ALCOHOLISM , *DRUG prescribing , *PSYCHOSES , *SLEEP disorders - Abstract
Aims To address the question of tailored baclofen prescribing in alcohol use disorder (AUD) in relation to dose-dependent efficacy and the potential danger of high doses and to provide suggestions for the use of high doses of baclofen in the treatment of AUD. The context is the approvement in France of baclofen in the treatment of AUD without dose limitation, making French physicians, who usually prescribe baclofen in a tailored manner, often use high or very high doses. Methods A narrative review of the results of randomized controlled trials (RCTs) and observational studies that used tailored baclofen prescribing and of the severe adverse effects of baclofen that have been reported in the literature. Results The results show that RCTs using tailored doses of baclofen in AUD are not completely demonstrative, though they are encouraging according to certain meta-analyses, while observational studies that used tailored doses constantly show a good effectiveness of baclofen treatment. The results suggest that many severe adverse effects of baclofen could be related to a nonrespect by physicians of prescription rules and appropriate treatment monitoring. Conclusions The use of tailored doses shows that the dose required to suppress cravings is highly variable, low or high, depending on each case. Analysis of the circumstances in which severe adverse effects occur suggest that a careful monitoring of baclofen prescribing might prevent a large majority of severe adverse effects. We propose that the education of the patients and the prescription skills, seriousness, and availability of the prescribing physicians are of major importance in the managing of tailored baclofen treatment of AUD. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Syncope in older adults: challenges, approach and treatment.
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Jansen, Sofie and van der Velde, Nathalie
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SYNCOPE , *LENGTH of stay in hospitals , *CAROTID sinus syndrome , *ORTHOSTATIC hypotension , *PATIENT satisfaction , *PATIENTS , *RISK assessment , *HOSPITAL admission & discharge , *ACCIDENTAL falls , *SEIZURES (Medicine) , *ARRHYTHMIA , *OLD age - Abstract
Syncope can have devastating consequences, resulting in injuries, accidents or even death. In our ageing society, the subsequent healthcare usage, such as emergency room presentations, surgeries and hospital admissions, forms a significant and growing socioeconomic burden. Causes of syncope in the older adult include orthostatic hypotension, carotid sinus syndrome, vasovagal syncope, structural cardiac abnormalities, cardiac arrhythmias and conduction abnormalities. As stated in the recently published World Falls Guidelines, syncope in older adults often presents as falls, which is either due to amnesia for loss of consciousness, or pre-syncope leading to a fall, especially in those prone to falls with several other risk-factors for falls present. This difference in presentation can hinder the recognition of syncope. In patients with unexplained falls, or in whom the history comprises red flags for potential syncope, special attention to (pre)syncope is therefore warranted. When syncope is mistaken for other causes of a transient loss of consciousness, such as epileptic seizures, or when syncope presents as falls, patients are often referred to multiple specialists, which may in turn lead to excessive and unnecessary diagnostic testing and costs. Specialist services that are able to provide a comprehensive assessment can improve diagnostic yield and minimise diagnostic testing, thus improving patient satisfaction. Comprehensive assessment also leads to reduced length of hospital stay. Increasingly, geriatricians are involved in the assessment of syncope in the older patient, especially given the overlap with falls. Therefore, awareness of causes of syncope, as well as state-of-the-art assessment and treatment, is of great importance. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Insulinoma Presenting as Seizures: Challenges of Managing a Rare Disease in a Resource-challenged Setting.
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Soyoye, David O, Atolani, Segun A, Adetunji, Tajudin A, and Alatise, Olusegun I
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INSULINOMA , *RARE diseases , *SEIZURES (Medicine) , *NEUROENDOCRINE tumors , *MAGNETIC resonance imaging , *BLOOD sugar - Abstract
Insulinomas are functioning pancreatic neuroendocrine tumors (NETs). They secrete insulin, and hence, present with hypoglycemia. We report a case of insulinoma in a 16-year-old girl presenting as seizures. She was initially managed at a private clinic and later commenced on carbamazepine when convulsion persisted. Convulsions were generalized, associated with dizziness and altered sensorium, often preceded by hunger and physical exertion, but relieved by the intake of carbonated drinks and fruit juice. She was referred to the neurology clinic when seizures persisted, despite the use of anticonvulsant. She was later referred to the endocrine clinic on suspicion of insulinoma when her random blood glucose (BG) was found to be low during an episode of convulsion. She was moderately obese but other examination findings were normal. She had a 72-hour prolonged fast, which was terminated when hypoglycemia (BG = 2.2 mmol/L) ensued after 12 hours, with elevated serum insulin and C-peptide. Abdominal magnetic resonance imaging scan showed a pancreatic tumor suggestive of insulinoma. She subsequently had distal pancreatectomy performed with complete resolution of symptoms. Unusual presentation of insulinoma may delay diagnosis, resulting in wastage of resources with increased morbidities and mortality. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Neuropsychiatric lupus in late- and early-onset systemic lupus erythematosus patients: a systematic review and meta-analysis.
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Pamuk, Omer Nuri, Raza, Ali Abbas, and Hasni, Sarfaraz
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SYSTEMIC lupus erythematosus diagnosis , *ONLINE information services , *MEDICAL databases , *NEUROPSYCHOLOGY , *META-analysis , *CONFIDENCE intervals , *PERIPHERAL neuropathy , *NEUROLOGICAL disorders , *SYSTEMATIC reviews , *AGE distribution , *PSYCHOSES , *DELAYED onset of disease , *NEUROBEHAVIORAL disorders , *AGE factors in disease , *DESCRIPTIVE statistics , *AFFECTIVE disorders , *RESEARCH funding , *MEDLINE , *ODDS ratio , *SEIZURES (Medicine) , *PROBABILITY theory - Abstract
Objectives Late-onset SLE is usually milder and associated with lower frequency of LN and neuropsychiatric manifestations. The diagnosis of NPSLE is especially challenging in older patients because of increased incidence of neurological comorbidities. We performed a systematic review and meta-analysis to evaluate the differences in NPSLE manifestations in early-onset (<50-year-old) vs late-onset (≥50-year-old) SLE patients. Methods A literature search was performed using the PubMed, Web of Science and Cochrane Library databases. Studies available in English (1959–2022) including a late-onset SLE comparison group and evaluating the frequency of NPSLE were eligible. A forest plot was used to compare odds ratios (95% CI) of incidence and manifestations of NPSLE by age groups. Study heterogeneity was assessed using I 2 statistics. Results A total of 44 studies, including 17 865 early-onset and 2970 late-onset SLE patients, fulfilled our eligibility criteria. CNS involvement was reported in 3326 patients. Cumulative NPSLE frequency was higher in the early-onset group than in the late-onset group (OR: 1.41, 95% CI: 1.24, 1.59, P < 0.0001). In early-onset SLE patients, seizures (OR: 1.68, 95% CI: 1.27, 2.22) and psychosis (OR: 1.72, 95% CI: 1.23, 2.41) were more common than in late-onset SLE patients (P values, 0.0003 and 0.0014, respectively). Peripheral neuropathy was more commonly reported in the late-onset SLE group than in the early-onset SLE group (OR: 0.64, 95% CI: 0.47, 0.86, P = 0.004). Conclusion Our meta-analysis revealed that the frequencies of overall NPSLE, seizures, and psychosis were less common in late-onset SLE patients than in early-onset SLE patients. In contrast, peripheral neuropathy was more common in the late-onset SLE group. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Correlations of receptor desensitization of gain-of-function GABRB3 variants with clinical severity.
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Lin, Susan X N, Ahring, Philip K, Keramidas, Angelo, Liao, Vivian W Y, Møller, Rikke S, Chebib, Mary, and Absalom, Nathan L
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EPILEPSY , *SEIZURES (Medicine) , *MOVEMENT disorders , *LENNOX-Gastaut syndrome , *GABA receptors , *GAIN-of-function mutations , *GENETIC variation , *INTELLECTUAL disabilities - Abstract
Genetic variants associated with developmental and epileptic encephalopathies have been identified in the GABRB3 gene that encodes the β3 subunit of GABAA receptors. Typically, variants alter receptor sensitivity to GABA resulting in either gain- or loss-of-function, which correlates with patient phenotypes. However, it is unclear how another important receptor property, desensitization, contributes to the greater clinical severity of gain-of-function variants. Desensitization properties of 20 gain-of-function GABRB3 variant receptors were evaluated using two-electrode voltage-clamp electrophysiology. The parameters measured included current decay rates and steady-state currents. Selected variants with increased or reduced desensitization were also evaluated using whole-cell electrophysiology in transfected mammalian cell lines. Of the 20 gain-of-function variants assessed, 13 were found to alter receptor desensitization properties. Seven variants reduced desensitization at equilibrium, which acts to worsen gain-of-function traits. Six variants accelerated current decay kinetics, which limits gain-of-function traits. All affected patients displayed severe clinical phenotypes with intellectual disability and difficult-to-treat epilepsy. Nevertheless, variants that reduced desensitization at equilibrium were associated with more severe clinical outcomes. This included younger age of first seizure onset (median 0.5 months), movement disorders (dystonia and dyskinesia), epilepsy of infancy with migrating focal seizures (EIMFS) and risk of early mortality. Variants that accelerated current decay kinetics were associated with slightly milder phenotypes with later seizure onset (median 4 months), unclassifiable developmental and epileptic encephalopathies or Lennox–Gastaut syndrome and no movement disorders. Our study reveals that gain-of-function GABRB3 variants can increase or decrease receptor desensitization properties and that there is a correlation with the degree of disease severity. Variants that reduced the desensitization at equilibrium were clustered in the transmembrane regions that constitute the channel pore and correlated with greater disease severity, while variants that accelerated current decay were clustered in the coupling loops responsible for receptor activation and correlated with lesser severity. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Delineating clinical and developmental outcomes in STXBP1-related disorders.
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Xian, Julie, Thalwitzer, Kim Marie, McKee, Jillian, Sullivan, Katie Rose, Brimble, Elise, Fitch, Eryn, Toib, Jonathan, Kaufman, Michael C, deCampo, Danielle, Cunningham, Kristin, Pierce, Samuel R, Goss, James, Rigby, Charlene Son, Syrbe, Steffen, Boland, Michael, Prosser, Benjamin, Fitter, Nasha, Ruggiero, Sarah M, and Helbig, Ingo
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EPILEPSY , *SEIZURES (Medicine) , *ADRENOCORTICOTROPIC hormone , *INFANTILE spasms , *ANTICONVULSANTS , *MISSENSE mutation - Abstract
STXBP1 -related disorders are among the most common genetic epilepsies and neurodevelopmental disorders. However, the longitudinal epilepsy course and developmental end points, have not yet been described in detail, which is a critical prerequisite for clinical trial readiness. Here, we assessed 1281 cumulative patient-years of seizure and developmental histories in 162 individuals with STXBP1 -related disorders and established a natural history framework. STXBP1 -related disorders are characterized by a dynamic pattern of seizures in the first year of life and high variability in neurodevelopmental trajectories in early childhood. Epilepsy onset differed across seizure types, with 90% cumulative onset for infantile spasms by 6 months and focal-onset seizures by 27 months of life. Epilepsy histories diverged between variant subgroups in the first 2 years of life, when individuals with protein-truncating variants and deletions in STXBP1 (n = 39) were more likely to have infantile spasms between 5 and 6 months followed by seizure remission, while individuals with missense variants (n = 30) had an increased risk for focal seizures and ongoing seizures after the first year. Developmental outcomes were mapped using milestone acquisition data in addition to standardized assessments including the Gross Motor Function Measure-66 Item Set and the Grasping and Visual-Motor Integration subsets of the Peabody Developmental Motor Scales. Quantification of end points revealed high variability during the first 5 years of life, with emerging stratification between clinical subgroups. An earlier epilepsy onset was associated with lower developmental abilities, most prominently when assessing gross motor development and expressive communication. We found that individuals with neonatal seizures or early infantile seizures followed by seizure offset by 12 months of life had more predictable seizure trajectories in early to late childhood compared to individuals with more severe seizure presentations, including individuals with refractory epilepsy throughout the first year. Characterization of anti-seizure medication response revealed age-dependent response over time, with phenobarbital, levetiracetam, topiramate and adrenocorticotropic hormone effective in reducing seizures in the first year of life, while clobazam and the ketogenic diet were effective in long-term seizure management. Virtual clinical trials using seizure frequency as the primary outcome resulted in wide range of trial success probabilities across the age span, with the highest probability in early childhood between 1 year and 3.5 years. In summary, we delineated epilepsy and developmental trajectories in STXBP1 -related disorders using standardized measures, providing a foundation to interpret future therapeutic strategies and inform rational trial design. [ABSTRACT FROM AUTHOR]
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- 2023
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23. Cell-type specific and multiscale dynamics of human focal seizures in limbic structures.
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Agopyan-Miu, Alexander H, Merricks, Edward M, Smith, Elliot H, McKhann, Guy M, Sheth, Sameer A, Feldstein, Neil A, Trevelyan, Andrew J, and Schevon, Catherine A
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EPILEPSY , *SEIZURES (Medicine) , *TEMPORAL lobe epilepsy , *PARTIAL epilepsy , *ACTION potentials - Abstract
The relationship between clinically accessible epileptic biomarkers and neuronal activity underlying the transition to seizure is complex, potentially leading to imprecise delineation of epileptogenic brain areas. In particular, the pattern of interneuronal firing at seizure onset remains under debate, with some studies demonstrating increased firing and others suggesting reductions. Previous study of neocortical sites suggests that seizure recruitment occurs upon failure of inhibition, with intact feedforward inhibition in non-recruited territories. We investigated whether the same principle applies in limbic structures. We analysed simultaneous electrocorticography (ECoG) and neuronal recordings of 34 seizures in a cohort of 19 patients (10 male, 9 female) undergoing surgical evaluation for pharmacoresistant focal epilepsy. A clustering approach with five quantitative metrics computed from ECoG and multiunit data was used to distinguish three types of site-specific activity patterns during seizures, which at times co-existed within seizures. Overall, 156 single units were isolated, subclassified by cell-type and tracked through the seizure using our previously published methods to account for impacts of increased noise and single-unit waveshape changes caused by seizures. One cluster was closely associated with clinically defined seizure onset or spread. Entrainment of high-gamma activity to low-frequency ictal rhythms was the only metric that reliably identified this cluster at the level of individual seizures (P < 0.001). A second cluster demonstrated multi-unit characteristics resembling those in the first cluster, without concomitant high-gamma entrainment, suggesting feedforward effects from the seizure. The last cluster captured regions apparently unaffected by the ongoing seizure. Across all territories, the majority of both excitatory and inhibitory neurons reduced (69.2%) or ceased firing (21.8%). Transient increases in interneuronal firing rates were rare (13.5%) but showed evidence of intact feedforward inhibition, with maximal firing rate increases and waveshape deformations in territories not fully recruited but showing feedforward activity from the seizure, and a shift to burst-firing in seizure-recruited territories (P = 0.014). This study provides evidence for entrained high-gamma activity as an accurate biomarker of ictal recruitment in limbic structures. However, reduced neuronal firing suggested preserved inhibition in mesial temporal structures despite simultaneous indicators of seizure recruitment, in contrast to the inhibitory collapse scenario documented in neocortex. Further study is needed to determine if this activity is ubiquitous to hippocampal seizures or indicates a 'seizure-responsive' state in which the hippocampus is not the primary driver. If the latter, distinguishing such cases may help to refine the surgical treatment of mesial temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]
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- 2023
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24. Proline-rich transmembrane protein 2 knock-in mice present dopamine-dependent motor deficits.
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Hatta, Daisuke, Kanamoto, Kaito, Makiya, Shiho, Watanabe, Kaori, Kishino, Tatsuya, Kinoshita, Akira, Yoshiura, Koh-Ichiro, Kurotaki, Naohiro, Shirotani, Keiro, and Iwata, Nobuhisa
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MEMBRANE proteins , *PROLINE , *DOPAMINERGIC neurons , *SEIZURES (Medicine) , *BASAL ganglia , *DOPAMINE receptors , *CEREBRAL cortex - Abstract
Mutations of proline-rich transmembrane protein 2 (PRRT2) lead to dyskinetic disorders such as paroxysmal kinesigenic dyskinesia (PKD), which is characterized by attacks of involuntary movements precipitated by suddenly initiated motion, and some convulsive disorders. Although previous studies have shown that PKD might be caused by cerebellar dysfunction, PRRT2 has not been sufficiently analyzed in some motor-related regions, including the basal ganglia, where dopaminergic neurons are most abundant in the brain. Here, we generated several types of Prrt2 knock-in (KI) mice harboring mutations, such as c.672dupG, that mimics the human pathological mutation c.649dupC and investigated the contribution of Prrt2 to dopaminergic regulation. Regardless of differences in the frameshift sites, all truncating mutations abolished Prrt2 expression within the striatum and cerebral cortex, consistent with previous reports of similar Prrt2 mutant rodents, confirming the loss-of-function nature of these mutations. Importantly, administration of l -dopa, a precursor of dopamine, exacerbated rotarod performance, especially in Prrt2 -KI mice. These findings suggest that dopaminergic dysfunction in the brain by the PRRT2 mutation might be implicated in a part of motor symptoms of PKD and related disorders. [ABSTRACT FROM AUTHOR]
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- 2023
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25. An integrated approach for early in vitro seizure prediction utilizing hiPSC neurons and human ion channel assays.
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Rockley, Kimberly, Roberts, Ruth, Jennings, Hannah, Jones, Karen, Davis, Myrtle, Levesque, Paul, and Morton, Michael
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ION channels , *NICOTINIC receptors , *GABA antagonists , *PLURIPOTENT stem cells , *SEIZURES (Medicine) , *GABA receptors , *VAGUS nerve , *CYTOLOGY , *HUMAN fingerprints - Abstract
Seizure liability remains a significant cause of attrition throughout drug development. Advances in stem cell biology coupled with an increased understanding of the role of ion channels in seizure offer an opportunity for a new paradigm in screening. We assessed the activity of 15 pro-seizurogenic compounds (7 CNS active therapies, 4 GABA receptor antagonists, and 4 other reported seizurogenic compounds) using automated electrophysiology against a panel of 14 ion channels (Nav1.1, Nav1.2, Nav1.6, Kv7.2/7.3, Kv7.3/7.5, Kv1.1, Kv4.2, KCa4.1, Kv2.1, Kv3.1, KCa1.1, GABA α1β2γ2, nicotinic α4β2, NMDA 1/2A). These were selected based on linkage to seizure in genetic/pharmacological studies. Fourteen compounds demonstrated at least one "hit" against the seizure panel and 11 compounds inhibited 2 or more ion channels. Next, we assessed the impact of the 15 compounds on electrical signaling using human-induced pluripotent stem cell neurons in microelectrode array (MEA). The CNS active therapies (amoxapine, bupropion, chlorpromazine, clozapine, diphenhydramine, paroxetine, quetiapine) all caused characteristic changes to electrical activity in key parameters indicative of seizure such as network burst frequency and duration. The GABA antagonist picrotoxin increased all parameters, but the antibiotics amoxicillin and enoxacin only showed minimal changes. Acetaminophen, included as a negative control, caused no changes in any of the parameters assessed. Overall, pro-seizurogenic compounds showed a distinct fingerprint in the ion channel/MEA panel. These studies highlight the potential utility of an integrated in vitro approach for early seizure prediction to provide mechanistic information and to support optimal drug design in early development, saving time and resources. [ABSTRACT FROM AUTHOR]
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- 2023
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26. Use of Levetiracetam for Post-Traumatic Seizure Prophylaxis in Combat-Related Traumatic Brain Injury.
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Atwood, Rex, Walker, Patrick, Walper, Daniel, Elster, Eric, and Bradley, Matthew
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BRAIN injuries , *LEVETIRACETAM , *GUNSHOT wounds , *EPILEPSY , *GLASGOW Coma Scale , *PREVENTIVE medicine , *SEIZURES (Medicine) - Abstract
Introduction Post-traumatic seizure (PTS) prophylaxis is recommended in patients with traumatic brain injury (TBI) at high risk for PTSs, but consensus on the optimal pharmacologic therapy has not yet been established. Levetiracetam is frequently used for seizure prophylaxis in combat-related TBI, but its efficacy and safety in this patient population has not yet been described. Methods A retrospective cohort of 687 consecutive casualties transferred to the CONUS from October 2010 to December 2015 was analyzed. Seventy-one patients with combat-related injuries and radiographic evidence of skull fractures or intracranial hemorrhage were included. Data collection included demographics and injury characteristics including initial Glasgow Coma Scale, computed tomography findings, interventions, and 6-month Glasgow Outcome Score. Results All patients in this cohort were male, with an average age of 25 (median 24; Interquartile range (IQR) 4.5) and an average Injury Severity Score of 28 (median 27; IQR 15). The most common mechanism of injury was explosive blast (76%). Penetrating TBI was common (51%). Most patients (88.7%) were administered seizure prophylaxis. Of these, the majority (61/63) received levetiracetam, and the additional two were administered phenytoin. The remaining 11.3% of patients were deemed not to require seizure prophylaxis. The incidence of seizures while on prophylaxis was low (2.8%) and occurred in patients who suffered transcranial gunshot wounds and ultimately died. No serious adverse effects were attributed to levetiracetam. Conclusions Levetiracetam appears to be a safe and effective medication for PTS prophylaxis in combat casualties. The rate of PTSs in combat-related TBI on appropriate prophylaxis is low. [ABSTRACT FROM AUTHOR]
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- 2023
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27. Endophthalmitis, Cutaneous Nodules, and Brain Lesions in Stem Cell Transplant Recipient.
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Axell-House, Dierdre B, Nagarajan, Priyadharsini, Bhatti, Micah M, Mehta, Rohtesh S, Roy, Shantanu, Ali, Ibne Karim M, and John, Teny M
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BRAIN , *PATIENTS , *MAGNETIC resonance imaging , *ENDOPHTHALMITIS , *PSYCHOSOCIAL factors , *HEMATOPOIETIC stem cell transplantation , *ACUTE erythroid leukemia , *SEIZURES (Medicine) , *TRANSPLANTATION of organs, tissues, etc. , *ORGAN donors - Abstract
The article presents a case study of a 46-year-old man with relapsed acute myeloid leukemia who underwent a second stem cell transplant from a matched related donor.It mentions that after the transplant, the patient developed various symptoms, including fever, sinusitis, eye issues, skin nodules, leukopenia, anemia, and thrombocytopenia.
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- 2023
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28. Optogenetic stimulation of the superior colliculus suppresses genetic absence seizures.
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Campos-Rodriguez, Carolina, Palmer, Devin, and Forcelli, Patrick A
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SUPERIOR colliculus , *SEIZURES (Medicine) , *DEEP brain stimulation , *ANTICONVULSANTS , *GENETIC models - Abstract
While anti-seizure medications are effective for many patients, nearly one-third of individuals have seizures that are refractory to pharmacotherapy. Prior studies using evoked preclinical seizure models have shown that pharmacological activation or excitatory optogenetic stimulation of the deep and intermediate layers of the superior colliculus (DLSC) display multi-potent anti-seizure effects. Here we monitored and modulated DLSC activity to suppress spontaneous seizures in the WAG/Rij genetic model of absence epilepsy. Female and male WAG/Rij adult rats were employed as study subjects. For electrophysiology studies, we recorded single unit activity from microwire arrays placed within the DLSC. For optogenetic experiments, animals were injected with virus coding for channelrhodopsin-2 or a control vector, and we compared the efficacy of continuous neuromodulation to that of closed-loop neuromodulation paradigms. For each, we compared three stimulation frequencies on a within-subject basis (5, 20, 100 Hz). For closed-loop stimulation, we detected seizures in real time based on the EEG power within the characteristic frequency band of spike-and-wave discharges (SWDs). We quantified the number and duration of each SWD during each 2 h-observation period. Following completion of the experiment, virus expression and fibre-optic placement was confirmed. We found that single-unit activity within the DLSC decreased seconds prior to SWD onset and increased during and after seizures. Nearly 40% of neurons displayed suppression of firing in response to the start of SWDs. Continuous optogenetic stimulation of the DLSC (at each of the three frequencies) resulted in a significant reduction of SWDs in males and was without effect in females. In contrast, closed-loop neuromodulation was effective in both females and males at all three frequencies. These data demonstrate that activity within the DLSC is suppressed prior to SWD onset, increases at SWD onset, and that excitatory optogenetic stimulation of the DLSC exerts anti-seizure effects against absence seizures. The striking difference between open- and closed-loop neuromodulation approaches underscores the importance of the stimulation paradigm in determining therapeutic effects. [ABSTRACT FROM AUTHOR]
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- 2023
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29. Parenteral medication considerations for the ketogenic diet.
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Abu-Sawwa, Renad, Busque, Katherine, and Cokley, Jon
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KETOGENIC diet , *PARENTERAL infusions , *QUALITY assurance , *NEEDS assessment , *SEIZURES (Medicine) , *PATIENT education - Abstract
Purpose This initiative conducted a needs assessment regarding the extent of potential risk for accidental carbohydrate exposure in patients on the ketogenic diet in acute care settings at 2 academic medical centers. Summary Medications used in the emergency department, intensive care unit, or operating room can contain carbohydrates or be diluted in carbohydrate-containing fluids. Use of these medications can shift patients on the ketogenic diet out of ketosis, causing breakthrough seizures. Despite standard clinical practices, there are no consensus guidelines to date for the logistical management of these patients during hospital admissions. This lack of standardized management increases the risk for parenteral medication errors during transitions within the healthcare system. A review of the literature demonstrates increased medication safety errors compounded by this lack of systemwide endeavors. Initiatives enhancing provider education and quality improvement safety measures have been reported; however, the extent of the potential risk with regard to medication formulation has not been assessed. Fifty medications were evaluated for their potential risk for carbohydrate exposure in a real-world quality improvement needs assessment conducted at 2 academic medical centers. Conclusion Because of increased exposure to carbohydrate-containing medications and medication safety errors, the authors recommend developing institutional protocols, an order set in the electronic medical record, and a multidisciplinary approach for patients on the ketogenic diet. Further research is warranted to assess the impact of these quality improvement measures on safety and clinical outcomes and to justify the development and implementation of consensus guidelines in centers of excellence that serve these patients. [ABSTRACT FROM AUTHOR]
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- 2023
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30. Precipitation of hyponatremia and seizures by esmolol in sterile water formulation.
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Zavala, Sarah, Kaminsky, Nicole, and Roels, Cathrine
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HALOTHERAPY , *ANTICONVULSANTS , *ELECTROENCEPHALOGRAPHY , *SODIUM , *HYPONATREMIA , *ESMOLOL , *HEALTH care teams , *SEIZURES (Medicine) , *PHARMACEUTICAL chemistry , *AORTIC dissection - Abstract
Purpose Acute hyponatremia can lead to severe neurological symptoms such as confusion, obtundation, seizures, coma, and respiratory depression, contributing to increased morbidity and mortality. Patients with acute hyponatremia should be evaluated based on volume status and serum osmolality to determine potential causes and appropriate treatment. The aim of this case report is to illustrate the importance of using a multidisciplinary approach to evaluate medication formulation and the potential impact on a patient's clinical course. Summary A 34-year-old male was admitted for type A aortic dissection and was treated with an esmolol infusion and underwent operative repair. Two days after initiation of esmolol, the patient developed seizures and antiepileptics were initiated. The patient's serum sodium concentration was found to have decreased by a total of 14 mEq/L since admission. The patient had received more than 6 L of esmolol formulated in sterile water over the course of 2 days. The esmolol infusion was converted to another antihypertensive agent, and 0.9% sodium chloride injection was initiated, after which the serum sodium concentration began to recover. No further seizures were observed on continuous electroencephalography, and all antiepileptic drugs were discontinued with no seizure activity. Conclusion The esmolol product utilized in this case was formulated in 250 mL of sterile water, which is suspected to have contributed to the patient's hyponatremia. It is important to be aware of the formulation and excipients of medications and their potential for adverse effects. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Juvenile idiopathic epilepsy in Arabian horses is not a single-gene disorder.
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Ciosek, Julia, Kimes, Abigail, Vinardell, Tatiana, Miller, Donald C, Antczak, Douglas F, and Brooks, Samantha
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ARABIAN horses , *GENOME-wide association studies , *SEIZURES (Medicine) , *EPILEPSY , *MONOGENIC & polygenic inheritance (Genetics) , *ANIMAL coloration - Abstract
Valued for their temperament, beauty, athletic ability, and exhibition in the show ring, Arabian horses are an important component of the horse industry. Juvenile idiopathic epilepsy (JIE), a seizure disorder, is most often reported in Arabian foals from birth to 6 months of age. Affected foals exhibit tonic–clonic seizures lasting as long as 5 min and risking secondary complications like temporary blindness and disorientation. Some foals outgrow this condition, while others die or suffer lifelong complications if not treated. Previous work suggested a strong genetic component to JIE and proposed JIE to be a single-gene trait. In this work, we conducted a genome wide association study (GWAS) in 60 cases of JIE and 120 genetically matched controls, identifying loci suggesting JIE is not caused by a single locus. Coat color (chestnut, gray) phenotypes were used as positive control traits to assess the efficacy of GWAS in this population. Future work will attempt to future define candidate regions and explore a polygenic mode of inheritance. [ABSTRACT FROM AUTHOR]
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- 2023
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32. A review of rheumatoid meningitis with case studies.
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Aktan Suzgun, Merve, Erener, Nursena, Cavus, Gokce Hande, Ozdede, Ayse, Guner, Sabriye, Ugurlu, Serdal, Comunoglu, Nil, Kizilkilic, Osman, and Saip, Sabahattin
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SARCOIDOSIS , *TUBERCULOUS meningitis , *SINGLE-photon emission computed tomography , *MENINGITIS , *SEIZURES (Medicine) - Published
- 2023
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33. Multisite thalamic recordings to characterize seizure propagation in the human brain.
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Wu, Teresa Q, Kaboodvand, Neda, McGinn, Ryan J, Veit, Mike, Davey, Zachary, Datta, Anjali, Graber, Kevin D, Meador, Kimford J, Fisher, Robert, Buch, Vivek, and Parvizi, Josef
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EPILEPSY , *SEIZURES (Medicine) , *PARTIAL epilepsy , *TEMPORAL lobectomy , *TEMPORAL lobe epilepsy , *THALAMIC nuclei , *EVOKED potentials (Electrophysiology) , *ELECTRIC stimulation - Abstract
Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in a subset of patients with refractory focal epilepsy. One important uncertainty is to what extent thalamic subregions other than the ANT could be recruited more prominently in the propagation of focal onset seizures. We designed the current study to simultaneously monitor the engagement of the ANT, mediodorsal (MD) and pulvinar (PUL) nuclei during seizures in patients who could be candidates for thalamic neuromodulation. We studied 11 patients with clinical manifestations of presumed temporal lobe epilepsy (TLE) undergoing invasive stereo-encephalography (sEEG) monitoring to confirm the source of their seizures. We extended cortical electrodes to reach the ANT, MD and PUL nuclei of the thalamus. More than one thalamic subdivision was simultaneously interrogated in nine patients. We recorded seizures with implanted electrodes across various regions of the brain and documented seizure onset zones (SOZ) in each recorded seizure. We visually identified the first thalamic subregion to be involved in seizure propagation. Additionally, in eight patients, we applied repeated single pulse electrical stimulation in each SOZ and recorded the time and prominence of evoked responses across the implanted thalamic regions. Our approach for multisite thalamic sampling was safe and caused no adverse events. Intracranial EEG recordings confirmed SOZ in medial temporal lobe, insula, orbitofrontal and temporal neocortical sites, highlighting the importance of invasive monitoring for accurate localization of SOZs. In all patients, seizures with the same propagation network and originating from the same SOZ involved the same thalamic subregion, with a stereotyped thalamic EEG signature. Qualitative visual reviews of ictal EEGs were largely consistent with the quantitative analysis of the corticothalamic evoked potentials, and both documented that thalamic nuclei other than ANT could have the earliest participation in seizure propagation. Specifically, pulvinar nuclei were involved earlier and more prominently than ANT in more than half of the patients. However, which specific thalamic subregion first demonstrated ictal activity could not be reliably predicted based on clinical semiology or lobar localization of SOZs. Our findings document the feasibility and safety of bilateral multisite sampling from the human thalamus. This may allow more personalized thalamic targets to be identified for neuromodulation. Future studies are needed to determine if a personalized thalamic neuromodulation leads to greater improvements in clinical outcome. [ABSTRACT FROM AUTHOR]
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- 2023
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34. Sleep and seizure risk in epilepsy: bed and wake times are more important than sleep duration.
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Stirling, Rachel E, Hidajat, Cindy M, Grayden, David B, D'Souza, Wendyl J, Naim-Feil, Jodie, Dell, Katrina L, Schneider, Logan D, Nurse, Ewan, Freestone, Dean, Cook, Mark J, and Karoly, Philippa J
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SLEEP duration , *BEDTIME , *SLEEP-wake cycle , *EPILEPSY , *SEIZURES (Medicine) - Abstract
Sleep duration, sleep deprivation and the sleep–wake cycle are thought to play an important role in the generation of epileptic activity and may also influence seizure risk. Hence, people diagnosed with epilepsy are commonly asked to maintain consistent sleep routines. However, emerging evidence paints a more nuanced picture of the relationship between seizures and sleep, with bidirectional effects between changes in sleep and seizure risk in addition to modulation by sleep stages and transitions between stages. We conducted a longitudinal study investigating sleep parameters and self-reported seizure occurrence in an ambulatory at-home setting using mobile and wearable monitoring. Sixty subjects wore a Fitbit smartwatch for at least 28 days while reporting their seizure activity in a mobile app. Multiple sleep features were investigated, including duration, oversleep and undersleep, and sleep onset and offset times. Sleep features in participants with epilepsy were compared to a large (n = 37 921) representative population of Fitbit users, each with 28 days of data. For participants with at least 10 seizure days (n = 34), sleep features were analysed for significant changes prior to seizure days. A total of 4956 reported seizures (mean = 83, standard deviation = 130) and 30 485 recorded sleep nights (mean = 508, standard deviation = 445) were included in the study. There was a trend for participants with epilepsy to sleep longer than the general population, although this difference was not significant. Just 5 of 34 participants showed a significant difference in sleep duration the night before seizure days compared to seizure-free days. However, 14 of 34 subjects showed significant differences between their sleep onset (bed) and/or offset (wake) times before seizure occurrence. In contrast to previous studies, the current study found undersleeping was associated with a marginal 2% decrease in seizure risk in the following 48 h (P < 0.01). Nocturnal seizures were associated with both significantly longer sleep durations and increased risk of a seizure occurring in the following 48 h. Overall, the presented results demonstrated that day-to-day changes in sleep duration had a minimal effect on reported seizures, while patient-specific changes in bed and wake times were more important for identifying seizure risk the following day. Nocturnal seizures were the only factor that significantly increased the risk of seizures in the following 48 h on a group level. Wearables can be used to identify these sleep–seizure relationships and guide clinical recommendations or improve seizure forecasting algorithms. [ABSTRACT FROM AUTHOR]
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- 2023
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35. Before Diagnosing SARS-CoV-2 Vaccination-Associated Immune Encephalitis Alternative Aetiologies Must Be Ruled Out.
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Finsterer, Josef
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GLIAL fibrillary acidic protein , *MAGNETIC resonance imaging , *NUCLEAR magnetic resonance spectroscopy , *INTRAVENOUS immunoglobulins , *SEIZURES (Medicine) - Abstract
This article discusses a case study of a 26-year-old man who developed immune encephalitis after receiving the second dose of the BNT162b2 COVID-19 vaccine. The patient experienced seizures, confusion, memory loss, and other cognitive changes. Treatment with anti-seizure medications, immunoglobulins, neuroleptics, and glucocorticoids was effective. However, the article raises several points that require further discussion, including the need to rule out other causes of encephalitis, the lack of immediate cerebral imaging after the first seizure, and the absence of certain tests and investigations. The study's limitations should be addressed before accepting its conclusions. [Extracted from the article]
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- 2024
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36. Frontal Lobe Lesion Masquerades as Meningioma.
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Peel, Joanne, Blazos, Mitsi, Manuchehri, Hossein, Fish, Charles, and Griffin, David W J
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DIAGNOSIS of brain diseases , *FRONTAL lobe surgery , *DNA analysis , *FRONTAL lobe , *TINNITUS , *NEUROSYPHILIS , *DIFFERENTIAL diagnosis , *IMMUNOASSAY , *PENICILLIN G , *TREATMENT effectiveness , *MENINGIOMA , *SEIZURES (Medicine) , *VISION disorders , *HEADACHE , *CRANIOTOMY , *POLYMERASE chain reaction - Abstract
The article presents the discussion on case study of 30-year-old overseas-born male with tonic–clonic seizure with no other systemic symptoms or head trauma. Topics include consulted his general practitioner, who prescribed a short course of oral cephalexin without further investigation; and lesion was discrete, appeared separate from adjacent brain tissue, and came away uniformly enbloc.
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- 2023
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37. Asymptomatic colo-ovarian fistula amidst acute psychosis: a case report.
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Mansour, Meghan R, Kessler, Steven A, Khreisat, Ali, and Skrzynski, Justin K
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FISTULA , *DIVERTICULITIS , *SEIZURES (Medicine) , *PSYCHOSES , *DIVERTICULOSIS , *BIPOLAR disorder - Abstract
This paper presents a rare case of an asymptomatic colo-ovarian fistula in a 45-year-old female with acute psychosis and a history of bipolar disorder, seizure disorder and substance misuse. The intricate diagnostic challenges arising from the patient's complex medical history underscore the significance of a multidisciplinary approach. The absence of typical gastrointestinal symptoms and the presence of a tubo-ovarian abscess complicated the diagnosis of acute on chronic sigmoid diverticulitis and colo-ovarian fistula. Surgical intervention, including sigmoid resection, anastomosis and left salpingo-oophorectomy, led to successful resolution. This case highlights the need for further understanding of colo-ovarian fistula pathophysiology, improved diagnostic strategies, and the nuanced interplay between medical and psychiatric conditions in complex clinical scenarios. [ABSTRACT FROM AUTHOR]
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- 2023
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38. Thalamostriatal disconnection underpins long-term seizure freedom in frontal lobe epilepsy surgery.
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Giampiccolo, Davide, Binding, Lawrence P, Caciagli, Lorenzo, Rodionov, Roman, Foulon, Chris, Tisi, Jane de, Granados, Alejandro, Finn, Roisin, Dasgupta, Debayan, Xiao, Fenglai, Diehl, Beate, Torzillo, Emma, Dijk, Jan Van, Taylor, Peter N, Koepp, Matthias, McEvoy, Andrew W, Baxendale, Sallie, Chowdhury, Fahmida, Duncan, John S, and Miserocchi, Anna
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FRONTAL lobe , *EPILEPSY surgery , *TEMPORAL lobectomy , *SEIZURES (Medicine) , *PARTIAL epilepsy , *EPILEPSY - Abstract
Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network. To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks. Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom. [ABSTRACT FROM AUTHOR]
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- 2023
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39. Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults.
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Ferreira-Atuesta, Carolina, Tisi, Jane de, McEvoy, Andrew W, Miserocchi, Anna, Khoury, Jean, Yardi, Ruta, Vegh, Deborah T, Butler, James, Lee, Hamin J, Deli-Peri, Victoria, Yao, Yi, Wang, Feng-Peng, Zhang, Xiao-Bin, Shakhatreh, Lubna, Siriratnam, Pakeeran, Neal, Andrew, Sen, Arjune, Tristram, Maggie, Varghese, Elizabeth, and Biney, Wendy
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EPILEPSY surgery , *TEMPORAL lobectomy , *PREDICTION models , *DRUGS , *SEIZURES (Medicine) , *ADULTS - Abstract
More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications (ASMs). We aimed to identify predictors of seizure recurrence after starting postoperative ASM withdrawal and develop and validate predictive models. We performed an international multicentre observational cohort study in nine tertiary epilepsy referral centres. We included 850 adults who started ASM withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting ASM withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of ASM withdrawal were focal non motor-aware seizures after surgery and before withdrawal (adjusted hazards ratio [aHR] 5.5, 95% confidence interval [CI] 2.7-11.1), history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9-2.8), time from surgery to the start of ASM withdrawal (aHR 0.9, 95% CI 0.8-0.9), and number of ASMs at time of surgery (aHR 1.2, 95% CI 0.9-1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63-0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64-0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models. We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.github.io), can provide probabilities of seizure outcomes after starting postoperative ASMs withdrawal. These multicentre-validated models may assist clinicians when discussing ASM withdrawal after surgery with their patients. [ABSTRACT FROM AUTHOR]
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- 2023
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40. Interictal discharges in the human brain are travelling waves arising from an epileptogenic source.
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Diamond, Joshua M, Withers, C Price, Chapeton, Julio I, Rahman, Shareena, Inati, Sara K, and Zaghloul, Kareem A
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EPILEPTIFORM discharges , *SEIZURES (Medicine) , *TEMPORAL lobectomy , *PEDIATRIC surgery , *EPILEPSY - Abstract
While seizure activity may be electrographically widespread, increasing evidence has suggested that ictal discharges may in fact represent travelling waves propagated from a focal seizure source. Interictal epileptiform discharges (IEDs) are an electrographic manifestation of excessive hypersynchronization of cortical activity that occur between seizures and are considered a marker of potentially epileptogenic tissue. The precise relationship between brain regions demonstrating IEDs and those involved in seizure onset, however, remains poorly understood. Here, we hypothesize that IEDs likewise reflect the receipt of travelling waves propagated from the same regions which give rise to seizures. Forty patients from our institution who underwent invasive monitoring for epilepsy, proceeded to surgery and had at least one year of follow-up were included in our study. Interictal epileptiform discharges were detected using custom software, validated by a clinical epileptologist. We show that IEDs reach electrodes in sequences with a consistent temporal ordering, and this ordering matches the timing of receipt of ictal discharges, suggesting that both types of discharges spread as travelling waves. We use a novel approach for localization of ictal discharges, in which time differences of discharge receipt at nearby electrodes are used to compute source location; similar algorithms have been used in acoustics and geophysics. We find that interictal discharges co-localize with ictal discharges. Moreover, interictal discharges tend to localize to the resection territory in patients with good surgical outcome and outside of the resection territory in patients with poor outcome. The seizure source may originate at, and also travel to, spatially distinct IED foci. Our data provide evidence that interictal discharges may represent travelling waves of pathological activity that are similar to their ictal counterparts, and that both ictal and interictal discharges emerge from common epileptogenic brain regions. Our findings have important clinical implications, as they suggest that seizure source localizations may be derived from interictal discharges, which are much more frequent than seizures. [ABSTRACT FROM AUTHOR]
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- 2023
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41. Monkeypox infections: seizures and encephalitis.
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He, G S -Y, Tay, S S -Y, Tan, B J -W, and Tan, E -K
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MONKEYPOX , *VIRAL encephalitis , *SEIZURES (Medicine) , *ENCEPHALITIS , *HAND, foot & mouth disease , *INFECTION - Abstract
The increased susceptibility of MPXV-associated encephalitis in young children highlights the need for a high index of suspicion since early MPXV infections can be confused with other common viral infections (such as hand foot and mouth disease) in this age group. In total, there were seven cases of encephalitis, in which three patients died while two made a full recovery.[[2], [4], [6]] The youngest patient recorded was only 28 days at birth, while the oldest patient recorded was 43 years old. The human monkeypox virus (MPXV), a member of the Orthopoxvirus genus, causes monkeypox, a re-emerging zoonotic viral disease that has a similar but less severe clinical presentation to smallpox.[1] While MPXV is endemic in African countries, the most recent outbreak has seen it spread to several countries. [Extracted from the article]
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- 2023
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42. Seizures in patients with kidney diseases: a neglected problem?
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Gungor, Ozkan, Aydin, Zeki, Inci, Ayca, Oguz, Ebru Gok, and Arici, Mustafa
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EPILEPSY , *KIDNEY diseases , *NEGLECTED diseases , *CHRONIC kidney failure , *ACUTE kidney failure , *SEIZURES (Medicine) , *LIMBIC system , *VAGUS nerve - Abstract
Nephrologists may encounter many systemic problems in their patients, including involvement of the neurological system and the development of seizures. Seizures are defined as abnormal neurological functions that cause overstimulation of neurons in the cerebral cortex or limbic system. Seizures may be focal or generalized depending on their origin and may have tonic, clonic, tonic–clonic or myoclonic character depending on the level of involvement of the motor movements. Patients with kidney disease may develop seizures due to etiologies seen in the general population (such as intracranial bleeding, cerebrovascular events, tumors, infections and intoxications) or due to kidney-related etiologies (such as uremic encephalopathy, dialysis disequilibrium syndrome and hyponatremia). Management of seizures in kidney patients is challenging for proper determination of the type and dosage of antiepileptic drugs due to varying renal clearances. This review covers the major causes of new-onset seizures in patients with acute kidney injury, electrolyte imbalances, chronic kidney disease, dialysis, renal transplantation or hypertension, and the available management approaches. [ABSTRACT FROM AUTHOR]
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- 2023
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43. La Crosse Virus Neuroinvasive Disease in Children: A Contemporary Analysis of Clinical/Neurobehavioral Outcomes and Predictors of Disease Severity.
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Boutzoukas, Angelique E, Freedman, Daniel A, Koterba, Christine, Hunt, Garrett W, Mack, Kathy, Cass, Jennifer, Yildiz, Vedat O, de los Reyes, Emily, Twanow, Jaime, Chung, Melissa G, and Ouellette, Christopher P
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EPIDEMIC encephalitis complications , *DIAGNOSIS of epilepsy , *PATIENT aftercare , *CONFIDENCE intervals , *ELECTROENCEPHALOGRAPHY , *EPIDEMIC encephalitis , *CROSS-sectional method , *RETROSPECTIVE studies , *NEUROLOGIC manifestations of general diseases , *SEVERITY of illness index , *RISK assessment , *RESEARCH funding , *QUESTIONNAIRES , *DESCRIPTIVE statistics , *EPILEPTIFORM discharges , *ODDS ratio , *SEIZURES (Medicine) , *LONGITUDINAL method , *MENTAL illness , *DISEASE complications , *CHILDREN - Abstract
Background La Crosse virus (LACV) is the most common neuroinvasive arboviral infection in children in the United States. However, data regarding predictors of disease severity and neurologic outcome are limited. Additionally, long-term neurologic and neurobehavioral outcomes remain relatively sparse. Methods This was a single-center, retrospective cohort study, followed by recruitment for a cross-sectional analysis of long-term neurobehavioral outcomes, among children aged 0–18 years with proven or probable LACV neuroinvasive disease (LACV-ND) between January 2009 and December 2018. Case ascertainment was assured by International Classification of Diseases , Ninth and Tenth Revision , Clinical Modification codes cross-referenced with laboratory results detecting LACV. Demographics, diagnostics, radiographs, and outcomes were evaluated. Recruitment of patients with prior diagnosis of LACV-ND occurred from January 2020 to March 2020, with assessment performed by validated pediatric questionnaires. Results One-hundred fifty-two children (83 males; median age, 8 years [interquartile range, 5–11.5 years]) were diagnosed with proven (n = 61 [47%]) and probable (n = 91 [60%]) LACV-ND. Sixty-five patients (43%) had severe disease. Altered mental status (AMS) (odds ratio [OR], 6.36 [95% confidence interval {CI}, 2.03–19.95]; P =.0002) and seizures at presentation (OR, 10.31 [95% CI, 3.45–30.86]; P =.0001) were independent predictors of severe disease. Epileptiform discharges on electroencephalogram (EEG) were independently associated with epilepsy diagnosis at follow-up (OR, 13.45 [95% CI, 1.4–128.77]; P =.024). Fifty-four patients were recruited for long-term neurobehavioral follow-up, with frequent abnormal assessments identified (19%–54%) irrespective of disease severity. Conclusions Severe disease was observed frequently among children with LACV-ND. Seizures and AMS at presentation were independent predictors of severe disease. EEG may help determine long-term epilepsy risk. Long-term neurobehavioral issues are frequent and likely underrecognized among children with LACV-ND. [ABSTRACT FROM AUTHOR]
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- 2023
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44. Distinct signatures of loss of consciousness in focal impaired awareness versus tonic-clonic seizures.
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Juan, Elsa, Górska, Urszula, Kozma, Csaba, Papantonatos, Cynthia, Bugnon, Tom, Denis, Colin, Kremen, Vaclav, Worrell, Greg, Struck, Aaron F, Bateman, Lisa M, Merricks, Edward M, Blumenfeld, Hal, Tononi, Giulio, Schevon, Catherine, and Boly, Melanie
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LOSS of consciousness , *SEIZURES (Medicine) , *EPILEPSY , *AWARENESS , *SYMPTOMS , *TEMPORAL lobe - Abstract
Loss of consciousness is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany loss of consciousness during focal impaired awareness seizures, the mechanisms of loss of consciousness during focal to bilateral tonic-clonic seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between focal impaired awareness and focal to bilateral tonic-clonic seizures may also help us to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of loss of consciousness and intracranial EEG activity during 129 focal impaired awareness and 50 focal to bilateral tonic-clonic from 41 patients. We characterized intracranial EEG changes both in the seizure onset zone and in areas remote from the seizure onset zone with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of intracranial EEG sleep-like activities: slow-wave activity (1-4 Hz) and beta/delta ratio (a validated marker of cortical activation) during focal impaired awareness versus focal to bilateral tonic-clonic. Second, we quantified differences between focal to bilateral tonic-clonic and focal impaired awareness for a marker validated to detect ictal cross-frequency coupling: phase-locked high gamma (high-gamma phased-locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index. Third, we assessed changes in intracranial EEG activity preceding and accompanying behavioural generalization onset and their correlation with electromyogram channels. In addition, we analysed human cortical multi-unit activity recorded with Utah arrays during three focal to bilateral tonic-clonic seizures. Compared to focal impaired awareness, focal to bilateral tonic-clonic seizures were characterized by deeper loss of consciousness, even before generalization occurred. Unlike during focal impaired awareness, early loss of consciousness before generalization was accompanied by paradoxical decreases in slow-wave activity and by increases in high-gamma activity in parieto-occipital and temporal cortex. After generalization, when all patients displayed loss of consciousness, stronger increases in slow-wave activity were observed in parieto-occipital cortex, while more widespread increases in cortical activation (beta/delta ratio), ictal cross-frequency coupling (phase-locked high gamma) and ictal recruitment (epileptogenicity index). Behavioural generalization coincided with a whole-brain increase in high-gamma activity, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of focal to bilateral tonic-clonic revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the seizure onset zone. Overall, these results indicate that unlike during focal impaired awareness, the neural signatures of loss of consciousness during focal to bilateral tonic-clonic consist of paradoxical increases in cortical activation and neuronal firing found most consistently in posterior brain regions. These findings suggest differences in the mechanisms of ictal loss of consciousness between focal impaired awareness and focal to bilateral tonic-clonic and may account for the more negative prognostic consequences of focal to bilateral tonic-clonic. [ABSTRACT FROM AUTHOR]
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- 2023
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45. Optimization of closed-loop electrical stimulation enables robust cerebellar-directed seizure control.
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Stieve, Bethany J, Richner, Thomas J, Krook-Magnuson, Chris, Netoff, Theoden I, and Krook-Magnuson, Esther
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ELECTRIC stimulation , *TEMPORAL lobe epilepsy , *KRIGING , *VAGUS nerve , *CEREBELLAR cortex , *SEIZURES (Medicine) , *ARTIFICIAL pancreases - Abstract
Additional treatment options for temporal lobe epilepsy are needed, and potential interventions targeting the cerebellum are of interest. Previous animal work has shown strong inhibition of hippocampal seizures through on-demand optogenetic manipulation of the cerebellum. However, decades of work examining electrical stimulation—a more immediately translatable approach—targeting the cerebellum has produced very mixed results. We were therefore interested in exploring the impact that stimulation parameters may have on seizure outcomes. Using a mouse model of temporal lobe epilepsy, we conducted on-demand electrical stimulation of the cerebellar cortex, and varied stimulation charge, frequency and pulse width, resulting in over 1000 different potential combinations of settings. To explore this parameter space in an efficient, data-driven, manner, we utilized Bayesian optimization with Gaussian process regression, implemented in MATLAB with an Expected Improvement Plus acquisition function. We examined three different fitting conditions and two different electrode orientations. Following the optimization process, we conducted additional on-demand experiments to test the effectiveness of selected settings. Regardless of experimental setup, we found that Bayesian optimization allowed identification of effective intervention settings. Additionally, generally similar optimal settings were identified across animals, suggesting that personalized optimization may not always be necessary. While optimal settings were effective, stimulation with settings predicted from the Gaussian process regression to be ineffective failed to provide seizure control. Taken together, our results provide a blueprint for exploration of a large parameter space for seizure control and illustrate that robust inhibition of seizures can be achieved with electrical stimulation of the cerebellum, but only if the correct stimulation parameters are used. [ABSTRACT FROM AUTHOR]
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- 2023
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46. Disease, disorder, condition or enigma? Epilepsy and its modern history re-examined.
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Boas, Walter van Emde
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EPILEPSY , *MODERN history , *SEIZURES (Medicine) , *HISTORY of medicine , *AGGRESSION (International law) , *PEOPLE with epilepsy - Abstract
Notably, they have also recently been renamed "anti-seizure drugs", rather than "anti-epileptic drugs" because the best they do is to suppress the seizures.[4] For the underlying epilepsy, so far no treatment is available. The section also includes two further appendices, one on the developments that have been "good" versus those that have been "bad" for epilepsy, and another on all the obsolete or failed theories and treatments associated with epilepsy. Throughout the book and for each time epoch he discusses epilepsy in a much wider context, effectively presenting not just a comprehensive history of epilepsy but also a broad history of medicine in its scientific, social and political context for the period 1800-2020. [Extracted from the article]
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- 2023
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47. Thalamic stereo-EEG in epilepsy surgery: where do we stand?
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Bernabei, John M, Litt, Brian, and Cajigas, Iahn
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EPILEPSY , *EPILEPSY surgery , *TEMPORAL lobectomy , *BRAIN stimulation , *SEIZURES (Medicine) , *LIMBIC system , *THALAMIC nuclei , *TEMPORAL lobe epilepsy - Abstract
Focal epilepsy also frequently involves the limbic system,[6] and for this reason these nuclei are the most appealing to study using SEEG in patients undergoing epilepsy surgery evaluation. This scientific commentary refers to 'Multisite thalamic recordings to characterize seizure propagation in the human brain' by Wu I et al. i (https://doi.org/10.1093/brain/awad121). [Extracted from the article]
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- 2023
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48. Compliance and Ketones Levels in Relation to Seizure Control in Children with Drug Resistant Epilepsy Treated with Ketogenic Diet.
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Shatla, Hamed M., Elgendy, Yasmin G., Shata, Mennatallah O., Ibrahim, Haya E., and Mohammed, Tasneem M.
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KETOGENIC diet , *LOW-fat diet , *EPILEPSY , *INBORN errors of metabolism , *LOW-carbohydrate diet , *SEIZURES (Medicine) - Abstract
Background: The ketogenic diet (KD) is a high-fat, adequate-protein, low-carbohydrate diet. Ketogenic diet therapy (KDT) has become an important option in the management of drug-resistant epilepsy and some of the inborn errors of metabolism in children, with increasing evidence of its favorable effects. Objective: To evaluate patient's compliance to KD in children with drug resistant epilepsy (DRE) and the effect of KD on course and outcome of DRE. Methodology: This cross-sectional study included 42 children whose age ranged between 1 month and 18 years with drug resistant epilepsy (DRE) on ketogenic diet for at least 3 months. They were recruited from the Ketogenic Diet Clinic, Children's hospital, Ain Shams University, Cairo, Egypt. They were assessed for anthropometric measurements, betahydroxybutyrate (BHB) in blood, and acetone in urine, fasting lipid profile, serum random blood sugar; The frequency and severity of convulsions were assessed using chalfont severity scale before and after applying KD and correlated with the laboratory markers measured. Results: Beta hydroxybutarate levels in blood ranged from (0.1 - 4.6) achieving ketosis in 37patient (BHB>2mmol/L). As regard frequency of convulsions per day there was highly significant decrease after 3 month of KD with p < 0.001 compared to that before using the KD. On applying chalfont seizure severity scale on our patients there was highly significant decrease in the severity of the seizure with p < 0.001 after KD. Regarding the frequency of possible complications associated with KD, 69% of the patients had no complication, while 26.2% had constipation, 26.2% had hyperlipidemia, 2.4 % had vomiting, 2.4 % had kidney stones, and 2.4 % had urinary gravels. Conclusion: KD is an effective, safe, and tolerable therapy for children with DRE where significant improvement in both frequency and severity of seizures after KD were found. [ABSTRACT FROM AUTHOR]
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- 2024
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49. Study of Inflammatory Markers in Patients with Uncontrolled Generalized Motor Tonic-Clonic Seizures.
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Lewis Andrawes, Amir Hani, El Rakawy, Mahmoud Hemeda, El Khayat, Naglaa Mohamed, and Abdelhamid, Yousry Aboelnaga
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EPILEPSY , *SEIZURES (Medicine) , *STATUS epilepticus , *NEUROLOGICAL disorders , *PLATELET lymphocyte ratio , *PEOPLE with epilepsy - Abstract
Background: Epilepsy is a multifaceted chronic neurological disease characterized by recurrent spontaneous seizures. It affects almost 70 million patients around the globe, making it one of the most common chronic causes of neurological morbidities. Aim of the Work: detect an association between some inflammatory markers {C-reactive protein (CRP), Neutrophil-lymphocyte ratio (NLR), and Platelet-lymphocyte ratio (PLR)) and epilepsy in order to detect a pathogenic relation that in turn can influence the course and management of epilepsy. Patients and Methods: the current body of evidence recognizes the association between inflammation and epilepsy. Several inflammatory markers have been investigated in relation to different types of epilepsy. This study chose CRP as a convenient and widely used inflammatory marker, together with NLR and PLR, the two novel, readily available indices of inflammation that are yet to be fully investigated in relation to epilepsy. We included 50 patients with uncontrolled generalized motor tonic-clonic seizures. Ages ranged from 18 - 45 years and both genders were represented. Patients were compared with 50 controls of same age and gender. Strict inclusion and exclusion criteria were applied to all volunteers. Results: In this study, levels of CRP, NLR and PLR in 50 patients with epilepsy were significantly higher than controls. These results add to the pool of evidence that support the association between epilepsy and inflammatory processes. This study managed to investigate the correlation between inflammatory markers and specific independent variables such as frequency of seizures, time interval between last seizure and presentation, number of status epilepticus per year, number of anti-epileptic medications, duration of postictal confusion, age of onset of seizures, duration of illness, and EEG findings, in addition to age and gender differences. This study found increased levels of CRP, NLR, and PLR in patients with high frequency seizures compared to those with intermittent seizures. Similar results were obtained with increased number of episodes of status epilepticus, number of anti-epileptic medications and shorter time interval between last reported seizure and sample withdrawal. Longer duration of postictal confusion was associated with high values of NLR and PLR. Conclusion: systemic inflammatory response has been detected in patients with uncontrolled generalized motor tonic-clonic seizures, which confirms the association between inflammation and epilepsy. This association is specifically correlated to higher seizure frequency, shorter duration between last seizure and blood sample withdrawal, higher number of status epilepticus in the last 12 months, higher number of anti-epileptic medications, longer duration of post-ictal confusion and female gender. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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50. Stimulating native seizures with neural resonance: a new approach to localize the seizure onset zone.
- Author
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Smith, Rachel J, Hays, Mark A, Kamali, Golnoosh, Coogan, Christopher, Crone, Nathan E, Kang, Joon Y, and Sarma, Sridevi V
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TRANSCRANIAL alternating current stimulation , *TEMPORAL lobectomy , *SEIZURES (Medicine) , *ELECTRIC stimulation , *EVOKED potentials (Electrophysiology) , *RESONANCE , *EPILEPSY surgery - Abstract
Successful outcomes in epilepsy surgery rely on the accurate localization of the seizure onset zone. Localizing the seizure onset zone is often a costly and time-consuming process wherein a patient undergoes intracranial EEG monitoring, and a team of clinicians wait for seizures to occur. Clinicians then analyse the intracranial EEG before each seizure onset to identify the seizure onset zone and localization accuracy increases when more seizures are captured. In this study, we develop a new approach to guide clinicians to actively elicit seizures with electrical stimulation. We propose that a brain region belongs to the seizure onset zone if a periodic stimulation at a particular frequency produces large amplitude oscillations in the intracranial EEG network that propagate seizure activity. Such responses occur when there is 'resonance' in the intracranial EEG network, and the resonant frequency can be detected by observing a sharp peak in the magnitude versus frequency response curve, called a Bode plot. To test our hypothesis, we analysed single-pulse electrical stimulation response data in 32 epilepsy patients undergoing intracranial EEG monitoring. For each patient and each stimulated brain region, we constructed a Bode plot by estimating a transfer function model from the intracranial EEG 'impulse' or single-pulse electrical stimulation response. The Bode plots were then analysed for evidence of resonance. First, we showed that when Bode plot features were used as a marker of the seizure onset zone, it distinguished successful from failed surgical outcomes with an area under the curve of 0.83, an accuracy that surpassed current methods of analysis with cortico-cortical evoked potential amplitude and cortico-cortical spectral responses. Then, we retrospectively showed that three out of five native seizures accidentally triggered in four patients during routine periodic stimulation at a given frequency corresponded to a resonant peak in the Bode plot. Last, we prospectively stimulated peak resonant frequencies gleaned from the Bode plots to elicit seizures in six patients, and this resulted in an induction of three seizures and three auras in these patients. These findings suggest neural resonance as a new biomarker of the seizure onset zone that can guide clinicians in eliciting native seizures to more quickly and accurately localize the seizure onset zone. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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