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Article ; Online: Pseudohyperkalemia due to cryohydrocytosis in GLUT1 deficiency syndrome. A case report and literature review.

Furia, Alessandro / Muccioli, Lorenzo / Santucci, Margherita / Licchetta, Laura / Bisulli, Francesca

Epileptic disorders : international epilepsy journal with videotape

2023 Volume 25, Issue 3, Page(s) 410–415

Abstract: Cryohydrocytosis is a form of stomatocytosis characterized by the leakage of sodium and potassium from red blood cells at low temperatures, characterized by pseudohyperkalemia. Stomatin-deficient cryohydrocytosis is an extremely rare variant that only ... ...

Abstract	Cryohydrocytosis is a form of stomatocytosis characterized by the leakage of sodium and potassium from red blood cells at low temperatures, characterized by pseudohyperkalemia. Stomatin-deficient cryohydrocytosis is an extremely rare variant that only recently has been related to pathogenic variants in the SLC2A1 gene, encoding the main glucose transporter of the blood-brain barrier and red blood cells, GLUT1. It follows that GLUT1 deficiency syndrome, a rare but significant cause of metabolic epilepsy, may present with stomatin-deficient cryohydrocytosis, although this correlation has only been reported in a few instances. We present the case of a patient carrying a novel de novo SLC2A1 pathogenic variant presenting with GLUT1 deficiency syndrome, pseudohyperkalemia, and splenomegaly consistent with cryohydrocytosis. We also review the previously reported cases of stomatin-deficient cryohydrocytosis in the literature. As highlighted by our case, elevated potassium levels are a cause of concern, and GLUT1 deficiency syndrome patients are thus at risk of being subjected to unnecessary examinations; pseudohyperkalemia may be underrecognized in clinical practice.
MeSH term(s)	Humans ; Hyperkalemia/diagnosis ; Hyperkalemia/etiology ; Epilepsy/genetics ; Potassium/metabolism
Chemical Substances	Potassium (RWP5GA015D)
Language	English
Publishing date	2023-04-27
Publishing country	United States
Document type	Case Reports ; Review ; Journal Article
ZDB-ID	2086797-9
ISSN	1950-6945 ; 1294-9361
ISSN (online)	1950-6945
ISSN	1294-9361
DOI	10.1002/epd2.20039
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Article ; Online: Current treatment options for familial adult myoclonus epilepsy.

Coppola, Antonietta / Dubbioso, Raffaele / Cuccurullo, Claudia / Licchetta, Laura / Carreno, Mar / Hirsch, Edouard / Bilo, Leonilda

Epilepsia

2023 Volume 64 Suppl 1, Page(s) S58–S63

Abstract: Familial adult myoclonus epilepsy (FAME) is a genetic condition characterized by the occurrence of cortical tremor, myoclonus, and epilepsy. To date, there is neither a curative nor a preventive treatment for FAME. Clinical management is essentially ... ...

Abstract	Familial adult myoclonus epilepsy (FAME) is a genetic condition characterized by the occurrence of cortical tremor, myoclonus, and epilepsy. To date, there is neither a curative nor a preventive treatment for FAME. Clinical management is essentially symptomatic and based on antiseizure medications (ASMs). The choice of the correct therapeutic option is limited to ASMs that have both an antiseizure and an antimyoclonic effect, such as valproate, levetiracetam, benzodiazepines, and perampanel. However, these medications control seizures well while having a limited effect on myoclonus and cortical tremor. In addition, many ASMs, including sodium channel blockers and gabapentin, are contraindicated in this condition. The ideal therapeutic option would be a precision treatment able to revert the genetic defect underlying it. Nevertheless, this does not seem to be an option that will be available soon.
MeSH term(s)	Adult ; Humans ; Myoclonus/drug therapy ; Tremor/drug therapy ; Epilepsy/drug therapy ; Epilepsies, Myoclonic/drug therapy ; Epilepsies, Myoclonic/genetics ; Valproic Acid/therapeutic use ; Anticonvulsants/therapeutic use
Chemical Substances	Valproic Acid (614OI1Z5WI) ; Anticonvulsants
Language	English
Publishing date	2023-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17590
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Article ; Online: MECP2

Cani, Ilaria / Muccioli, Lorenzo / Mignani, Francesco / Licchetta, Laura / Tinuper, Paolo / Provini, Federica / Bisulli, Francesca

Epilepsy & behavior reports

2022 Volume 19, Page(s) 100541

Abstract: MECP2 duplication syndrome (MDS) is a rare and severe neurodevelopmental disorder frequently associated with epilepsy. Different seizure types and electroencephalographic (EEG) patterns were described in patients with MDS, although it lacks a specific ... ...

Abstract	MECP2 duplication syndrome (MDS) is a rare and severe neurodevelopmental disorder frequently associated with epilepsy. Different seizure types and electroencephalographic (EEG) patterns were described in patients with MDS, although it lacks a specific phenotype. We report on an adult patient with long-term epilepsy showing an evolution of the EEG pattern that progressively changed into burst suppression (BS) during sleep. As BS has not been previously reported in MDS, this report expands the neurophysiological phenotype of MDS and further suggest the possible occurrence of a longitudinal spectrum of seizure types and EEG patterns in MDS.
Language	English
Publishing date	2022-04-19
Publishing country	United States
Document type	Case Reports
ISSN	2589-9864
ISSN (online)	2589-9864
DOI	10.1016/j.ebr.2022.100541
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Article ; Online: Clinical characterization of non-ketotic hyperglycemia-related seizures: A systematic review and individual participant data meta-analysis.

Licchetta, Laura / Ferri, Lorenzo / Morsillo, Filomena / Faustini-Fustini, Marco / Toni, Francesco / Pondrelli, Federica / Nonino, Francesco / Bisulli, Francesca / Tinuper, Paolo

Seizure

2023 Volume 106, Page(s) 50–57

Abstract: New-onset epileptic seizures and status epilepticus (SE) are the most frequent neurological manifestations of non-ketotic hyperglycemia (NKH), an acute complication of diabetes mellitus (DM). Treatment consists of the correction of the underlying ... ...

Abstract	New-onset epileptic seizures and status epilepticus (SE) are the most frequent neurological manifestations of non-ketotic hyperglycemia (NKH), an acute complication of diabetes mellitus (DM). Treatment consists of the correction of the underlying metabolic disorder, whereas anti-seizure medications (ASMs) may even worsen seizures. Evidence on NKH-related seizures is currently restricted to case reports and small case-series. We conducted a systematic review of the PubMed, Embase, and Cochrane Library databases to provide a comprehensive description of NKH-related seizures. Statistical analyses were performed to explore possible associations of glycemic and osmolarity levels with clinical variables. We selected 130 publications and 332 patients (186 males, mean age: 61.1 years). DM was newly-diagnosed in 40%. Mean glycemia and osmolarity levels at presentation were 529.7 mg/dL and 309.6 mmol/mol, respectively; 22.6% showed other neurological symptoms besides seizures. Focal motor seizures were the prominent seizure type (49.4%); non-motor focal seizures (23.2%) most commonly manifested as visual symptoms. Reflex seizures occurred in 10.5%. Brain MRI in 48.7% of cases showed focal T2 subcortical hypodensity and/or overlying cortical T2 hyperintensity with DWI restriction. ASMs were administered in 54.2% of cases, achieving seizure control in just 18.3%. Higher osmolarity levels were associated with newly-diagnosed DM (p = 0.002) and other symptoms at presentation (p < 0.001). Glycemic values were higher in patients with focal aware seizures with motor onset compared to those with focal seizures without motor onset (p = 0.0046) or focal seizures with impaired awareness (p = 0.0306). Lower glycemic values were associated with reflex seizures (p = 0.036) and ASM administration (p < 0.001). NKH-related seizures should be suspected in adults with new-onset clustering focal seizures arising from the motor or posterior cortices, even in the absence of a history of DM. Typical focal changes on brain MRI, while not pathognomonic, can drive the clinical diagnosis. Statistical associations suggest a key role of hyperglycemia in the excitability of higher-energy-demanding cortical areas.
MeSH term(s)	Male ; Adult ; Humans ; Middle Aged ; Epilepsy/complications ; Hyperglycemia/complications ; Hyperglycemia/drug therapy ; Epilepsies, Partial/drug therapy ; Status Epilepticus/complications ; Ketosis
Language	English
Publishing date	2023-01-27
Publishing country	England
Document type	Systematic Review ; Meta-Analysis ; Journal Article ; Review
ZDB-ID	1137610-7
ISSN	1532-2688 ; 1059-1311
ISSN (online)	1532-2688
ISSN	1059-1311
DOI	10.1016/j.seizure.2023.01.018
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Article ; Online: Biallelic pathogenic variants of PARS2 cause developmental and epileptic encephalopathy with spike-and-wave activation in sleep.

Licchetta, Laura / Di Giorgi, Lucia / Santucci, Margherita / Taruffi, Lisa / Stipa, Carlotta / Minardi, Raffaella / Carelli, Valerio / Bisulli, Francesca

Molecular genetics & genomic medicine

2023 Volume 12, Issue 1, Page(s) e2311

Abstract: Background: Biallelic pathogenic variants in the mitochondrial prolyl-tRNA synthetase 2 gene (PARS2, OMIM * 612036) have been associated with Developmental and Epileptic Encephalopathy-75 (DEE-75, MIM #618437). This condition is typically characterized ... ...

Abstract	Background: Biallelic pathogenic variants in the mitochondrial prolyl-tRNA synthetase 2 gene (PARS2, OMIM * 612036) have been associated with Developmental and Epileptic Encephalopathy-75 (DEE-75, MIM #618437). This condition is typically characterized by early-onset refractory infantile spasms with hypsarrhythmia, intellectual disability, microcephaly, cerebral atrophy with hypomyelination, lactic acidemia, and cardiomyopathy. Most affected individuals do not survive beyond the age of 10 years. Methods: We describe a patient with early-onset DEE, consistently showing an EEG pattern of Spike-and-Wave Activation in Sleep (SWAS) since childhood. The patient underwent extensive clinical, metabolic and genetic investigations, including whole exome sequencing (WES). Results: WES analysis identified compound heterozygous variants in PARS2 that have been already reported as pathogenic. A literature review of PARS2-associated DEE, focusing mainly on the electroclinical phenotype, did not reveal the association of SWAS with pathogenic variants in PARS2. Notably, unlike previously reported cases with the same genotype, this patient had longer survival without cardiac involvement or lactic acidosis, suggesting potential genetic modifiers contributing to disease variability. Conclusion: These findings widen the genetic heterogeneity of DEE-SWAS, including PARS2 as a causative gene in this syndromic entity, and highlight the importance of prolonged sleep EEG recording for the recognition of SWAS as a possible electroclinical evolution of PARS2-related DEE.
MeSH term(s)	Humans ; Child ; Spasms, Infantile/genetics ; Sleep/physiology ; Microcephaly ; Electroencephalography ; Phenotype
Language	English
Publishing date	2023-12-13
Publishing country	United States
Document type	Case Reports ; Review ; Journal Article
ZDB-ID	2734884-2
ISSN	2324-9269 ; 2324-9269
ISSN (online)	2324-9269
ISSN	2324-9269
DOI	10.1002/mgg3.2311
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Article: A Male Child with Infantile Epilepsy due to a Mosaic Missense Variant of PCDH19.

Parmeggiani, Giulia / Minardi, Raffaella / Boni, Antonella / Pruccoli, Jacopo / Pini, Antonella / Licchetta, Laura / Bisulli, Francesca / Graziano, Claudio / Seri, Marco

Molecular syndromology

2023 Volume 15, Issue 2, Page(s) 114–118

Abstract: Background: Pathogenic variants of PCDH19, located on the X-chromosome (Xq22.1), cause a rare epileptic encephalopathy with speech and development delay, seizures, behavioral and psychiatric problems. The specific underlying pathogenic mechanism is ... ...

Abstract	Background: Pathogenic variants of PCDH19, located on the X-chromosome (Xq22.1), cause a rare epileptic encephalopathy with speech and development delay, seizures, behavioral and psychiatric problems. The specific underlying pathogenic mechanism is known as "cellular interference" that results in affected heterozygous females, normal hemizygous males and affected mosaic males but its functioning is not yet clear. Objectives: Reporting new cases of affected males is considered useful to a deeper insight. Subject and method: We present the case of a three-year-old boy with early-onset seizures at 3 months of age, mild cognitive impairment, partial control of seizures with levetiracetam, normal brain imaging. Results: The patient has a mosaic pathogenic variant c.698A>G (p.Asp233Gly) in PCDH19 assessed by Next Generation Sequencing analysis. We have compared his characteristics with the genotypes and phenotypes of 34 PCDH19 mosaic males earlier reported in the literature. Finally, we have summarized today's knowledge about phenotype-genotype correlation and pharmacological response in these patients. Conclusions: Our report confirms that the clinical picture of mosaic affected males, resembling that of females, can show a wide variability in severity of disease and underlines a stringent need to improve therapeutic approaches and to collect data on long-term follow-up.
Language	English
Publishing date	2023-12-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2546218-0
ISSN	1661-8777 ; 1661-8769
ISSN (online)	1661-8777
ISSN	1661-8769
DOI	10.1159/000535144
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Article ; Online: Tuberous sclerosis complex in adulthood: focus on epilepsy prognosis.

Licchetta, Laura / Bruschi, Giulia / Stipa, Carlotta / Belotti, Laura Maria Beatrice / Ferri, Lorenzo / Mostacci, Barbara / Vignatelli, Luca / Minardi, Raffaella / Di Vito, Lidia / Muccioli, Lorenzo / Boni, Antonella / Tinuper, Paolo / Bisulli, Francesca

Epilepsy & behavior : E&B

2024 Volume 153, Page(s) 109688

Abstract: Objective: Typically diagnosed in early childhood or adolescence, TSC is a chronic, multisystemic disorder with age-dependent manifestations posing a challenge for transition and for specific surveillance throughout the lifetime. Data on the clinical ... ...

Abstract	Objective: Typically diagnosed in early childhood or adolescence, TSC is a chronic, multisystemic disorder with age-dependent manifestations posing a challenge for transition and for specific surveillance throughout the lifetime. Data on the clinical features and severity of TSC in adults and on the prognosis of epilepsy are scarce. We analyzed the clinical and genetic features of a cohort of adult patients with TSC, to identify the prognostic predictors of seizure remission after a long follow-up. Method: We conducted a retrospective analysis of patients diagnosed with TSC according to the updated international diagnostic criteria. Pearson's chi-square or Fisher's exact test and Mann Whitney U test were used to compare variables among the Remission (R) and Non-Remission (NR) group. Univariate and multivariate logistic regression analyses were performed. Results: We selected 43 patients with TSC and neurological involvement in terms of epilepsy and/or brain lesions, attending the Epilepsy Center of our Institute: of them, 16 (37.2%) were transitioning from the pediatric care and 6 (13.9%) were referred by other specialists. Multiorgan involvement includes cutaneous (86.0%), nephrological (70.7%), hepatic (40.0%), ocular (34.3%), pneumological (28.6%) and cardiac (26.3%) manifestations. Thirty-nine patients (90.7 %) had epilepsy. The mean age at seizure onset was 4 ± 7.3 years: most patients (29, 76.3 %) presented with focal seizures or spasms by age 3 years; only 2 (5.3 %) had seizure onset in adulthood. Twenty-seven patients (69.2 %) experienced multiple seizure types overtime, 23 (59.0 %) had intellectual disability (ID). At last assessment, 14 (35.9 %) were seizure free (R group) and 25 (64.1 %) had drug-resistant seizures (NR group). At logistic regression univariate analysis, ID (OR 7.9, 95 % CI 1.8--34.7), multiple seizure types lifelong (OR 13.2, 95 % CI 2.6- 67.2), spasms/tonic seizures at presentation (OR 6.5, 95 % CI 1.2--35.2), a higher seizure frequency at onset (OR 5.4, 95 % CI 1.2--24.3), abnormal neurological examination (OR 9.8, 95 % CI 1.1--90.6) and pathogenic variants in TSC2 (OR 5.4, 95 % CI 1.2--24.5) were significantly associated with non-remission. In the multivariate analysis, both ID and multiple seizure types lifelong were confirmed as independent predictors of poor seizure outcome. Conclusions: In our cohort of adult patients with TSC, epilepsy remains one of the main neurological challenges with only 5.3% of cases manifesting in adulthood. Approximately 64% of these patients failed to achieve seizure remission. ID and multiple seizure types were the main predictors of poor outcome. Nephrological manifestations require continuous specific follow-up in adults.
MeSH term(s)	Child ; Adult ; Adolescent ; Humans ; Child, Preschool ; Anticonvulsants/therapeutic use ; Tuberous Sclerosis/complications ; Tuberous Sclerosis/genetics ; Tuberous Sclerosis/drug therapy ; Retrospective Studies ; Epilepsy/etiology ; Epilepsy/complications ; Seizures/drug therapy ; Prognosis ; Spasm
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2010587-3
ISSN	1525-5069 ; 1525-5050
ISSN (online)	1525-5069
ISSN	1525-5050
DOI	10.1016/j.yebeh.2024.109688
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Article ; Online: Fingerprick volumetric absorptive microsampling for therapeutic drug monitoring of antiseizure medications: Reliability and real-life feasibility in epilepsy patients.

Cancellerini, Chiara / Belotti, Laura Maria Beatrice / Mohamed, Susan / Solda', Martina / Esposito, Erika / Bisulli, Francesca / Mostacci, Barbara / Vignatelli, Luca / Tinuper, Paolo / Contin, Manuela / Licchetta, Laura

Journal of pharmaceutical and biomedical analysis

2024 Volume 242, Page(s) 116065

Abstract: Volumetric absorptive microsampling (VAMS) is increasingly proposed as a clinically reliable therapeutic drug monitoring (TDM) sampling methodology. The study aimed to establish the reliability and real-life feasibility of patient self-collected ... ...

Abstract	Volumetric absorptive microsampling (VAMS) is increasingly proposed as a clinically reliable therapeutic drug monitoring (TDM) sampling methodology. The study aimed to establish the reliability and real-life feasibility of patient self-collected capillary VAMS for TDM of antiseizure medication (ASMs), using plasma ASMs concentrations from venous blood as a reference standard. Nurses collected venous and capillary blood samples using VAMS. Afterward, persons with epilepsy (PWE) performed VAMS sampling by themselves. All samples were analyzed by UHPLC-MS/MS. We performed a cross-validation study, comparing ASMs concentrations obtained by VAMS nurses and patients' self-collected versus plasma through Bland-Altman analysis and Passing-Bablok regression. We enrolled 301 PWE (M: F 42.5%:57.5%; mean age 44±16 years), treated with 13 ASMs, providing a total of 464 measurements. Statistical analysis comparing VAMS self-collected versus plasma ASMs concentrations showed a bias close to zero and slope and intercept values indicating a good agreement for CBZ, LCS, LEV, LTG, OXC, PB, and PHT, while a systematic difference between the two methods was found for VPA, PMP, TPM and ZNS. This is the first study showing the reliability and feasibility of the real-world application of PWE self-collected VAMS for most of the ASMs considered, giving a promising basis for at-home VAMS applications.
MeSH term(s)	Humans ; Adult ; Middle Aged ; Tandem Mass Spectrometry/methods ; Drug Monitoring/methods ; Reproducibility of Results ; Feasibility Studies ; Blood Specimen Collection/methods ; Dried Blood Spot Testing/methods ; Epilepsy/drug therapy
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Journal Article
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2024.116065
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Article: Ictal Bradycardia and Asystole in Sleep-Related Hypermotor Epilepsy: A Study of 200 Patients.

Muccioli, Lorenzo / Bruschi, Giulia / Ferri, Lorenzo / Scarabello, Anna / Taruffi, Lisa / Di Vito, Lidia / Mostacci, Barbara / Provini, Federica / Calandra-Buonaura, Giovanna / Tinuper, Paolo / Licchetta, Laura / Bisulli, Francesca

Journal of clinical medicine

2024 Volume 13, Issue 6

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2024-03-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13061767
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Article: Epilepsy With Auditory Features: From Etiology to Treatment.

Furia, Alessandro / Licchetta, Laura / Muccioli, Lorenzo / Ferri, Lorenzo / Mostacci, Barbara / Mazzoni, Stefania / Menghi, Veronica / Minardi, Raffaella / Tinuper, Paolo / Bisulli, Francesca

Frontiers in neurology

2022 Volume 12, Page(s) 807939

Abstract: Epilepsy with auditory features (EAF) is a focal epilepsy belonging to the focal epileptic syndromes with onset at variable age according to the new ILAE Classification. It is characterized by seizures with auditory aura or receptive aphasia suggesting a ...

Abstract	Epilepsy with auditory features (EAF) is a focal epilepsy belonging to the focal epileptic syndromes with onset at variable age according to the new ILAE Classification. It is characterized by seizures with auditory aura or receptive aphasia suggesting a lateral temporal lobe involvement of the epileptic discharge. Etiological factors underlying EAF are largely unknown. In the familial cases with an autosomal dominant pattern of inheritance several genes have been involved, among which the first discovered,
Language	English
Publishing date	2022-01-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2021.807939
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