Publications by authors named "Carlo Di Bonaventura"

117 Publications

Epilepsy in "Sunflower syndrome": electroclinical features, therapeutic response, and long-term follow-up.

Seizure 2021 Oct 2;93:8-12. Epub 2021 Oct 2.

Department of Pediatrics, University of Perugia, Italy.

Background: Sunflower syndrome (SFS) is a rare childhood-onset generalized epilepsy characterized by photosensitivity, heliotropism, and drug-resistant stereotyped seizures maybe self-induced by hand-waving maneuvers. Data on the long-term prognosis are scantly and evidence over best treatment strategies is lacking.

Methods: We retrospectively describe the electroclinical features, and therapeutic response in a group of 21 patients with SFS, without intellectual disability.

Results: 16 patients were female (67%), with a median age at onset of 7 years. In all patients, ictal episodes began with sun-staring, and hand-waving in front of the sunlight, accompanied by brief typical absence seizures. 17 patients (81%) showed interictal EEG abnormalities, mainly characterized by spike and polyspike-and-wave discharges. Ictal epileptiform activity occurred approximately less than one second after the start of hand-waving. At the last follow-up (median length 8.2 years), 12 patients (57%) were drug-resistant. Nine of them (75%) achieved seizure control with the use of tainted lenses, either alone or compared with anti-seizure medications (ASM). Disappearance of seizures was associated with EEG improvement/normalization when tinted glasses were used during EEG recordings.

Conclusion: While the clinical and EEG characteristics of SFS are well defined, the best therapeutic approaches are still under debate. Our data confirms a high rate of drug-resistance and frequent need of polytherapy. Of note, in drug-resistant patients, lenses (but not ASM) were able to suppress PPR in our patients while wearing lenses. Regarding the role of lenses, we do not only rely on the PPR reduction but also clinically by the reduction of seizures. Although additional data are needed, lenses seem to have a powerful potential role for the management of SFS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2021.09.021DOI Listing
October 2021

Musicogenic epilepsy in paraneoplastic limbic encephalitis: a video-EEG case report.

Epileptic Disord 2021 Oct;23(5):754-759

Epilepsy Centre, Department of Human Neurosciences, "Sapienza" University of Rome, Rome.

Musicogenic epilepsy (ME), a peculiar form of reflex epilepsy, represents a neurological rarity and yet another demonstration of the extraordinary power of music on the human brain. Despite the heterogeneity of the reported musical triggers, patients' emotional response to music is thought to play a crucial role in provoking seizures. Accordingly, the mesial temporal structures (especially of the non-dominant hemisphere) appear most involved in seizure generation, although a more complex fronto-temporal epileptogenic network was documented in some cases. Autoimmune encephalitis has been recently included among the many possible aetiologies of ME based on a few reports of music-induced seizures in patients with anti-glutamic acid decarboxylase 65 antibodies. Here, we describe the case of a 25-year-old man, educated in music over a long period of time, who had suffered from drug-resistant temporal lobe epilepsy following seronegative limbic encephalitis related to non-Hodgkin lymphoma. Along with spontaneous events, the patient also developed musicogenic seizures later in the disease course. After detecting five music-induced episodes via 24-hour ambulatory EEG, we performed prolonged video-EEG monitoring during which the patient presented a right temporal seizure (characterized by déjà-vu, piloerection and gustatory hallucinations) while listening to a hard rock song through headphones (which he had not previously heard). This observation allowed us to confirm the provoking effect of the music on our patient's seizures, despite the lack of any emotional drive, which suggests that a "cognitive" trigger was more likely in this case. Our report further highlights that autoimmune encephalitis should be investigated as a novel potential cause of musicogenic epilepsy, regardless of autoantibody status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2021.1322DOI Listing
October 2021

Unilateral catalepsy in non-convulsive status epilepticus.

Epileptic Disord 2021 Oct;23(5):760-764

Epilepsy Unit, Department of Human Neurosciences, "Sapienza" University of Rome, Rome, Italy.

Catalepsy is defined as a loss of motor and it is listed among the clinical features associated with catatonic syndrome and may occur in association with both psychiatric and neurological disorders. Isolated catalepsy represents a much rarer phenomenon, and has been occasionally reported due to focal brain injuries (e.g. strokes) involving either cortical or subcortical regions. Here, we describe the case of an 81-year-old man presenting with isolated unilateral catalepsy as the main manifestation of focal non-convulsive status epilepticus, ipsilateral to the cataleptic limbs. To our knowledge, this is the first report of ictal catalepsy, which highlights the need to consider epilepsy in the diagnostic algorithm for both hyper- and hypokinetic movement disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2021.1323DOI Listing
October 2021

Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST).

CNS Drugs 2021 Sep 2. Epub 2021 Sep 2.

Department of Human Neurosciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile.

Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice.

Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure-freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed.

Results: A total of 1029 patients with a median age of 45 years (33-56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p < 0.001); the corresponding values for ≥ 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%; p = 0.341) and seizure response (39.7% vs. 26.9%; p = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p = 0.017).

Conclusion: The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40263-021-00856-3DOI Listing
September 2021

Molecular Chaperones and miRNAs in Epilepsy: Pathogenic Implications and Therapeutic Prospects.

Int J Mol Sci 2021 Aug 10;22(16). Epub 2021 Aug 10.

Department of Biomedicine, Neuroscience and Advanced Diagnostics, Section of Human Anatomy, University of Palermo, 90127 Palermo, Italy.

Epilepsy is a pathologic condition with high prevalence and devastating consequences for the patient and its entourage. Means for accurate diagnosis of type, patient monitoring for predicting seizures and follow up, and efficacious treatment are desperately needed. To improve this adverse outcome, miRNAs and the chaperone system (CS) are promising targets to understand pathogenic mechanisms and for developing theranostics applications. miRNAs implicated in conditions known or suspected to favor seizures such as neuroinflammation, to promote epileptic tolerance and neuronal survival, to regulate seizures, and others showing variations in expression levels related to seizures are promising candidates as useful biomarkers for diagnosis and patient monitoring, and as targets for developing novel therapies. Components of the CS are also promising as biomarkers and as therapeutic targets, since they participate in epileptogenic pathways and in cytoprotective mechanisms in various epileptogenic brain areas, even if what they do and how is not yet clear. The data in this review should help in the identification of molecular targets among the discussed miRNAs and CS components for research aiming at understanding epileptogenic mechanisms and, subsequently, develop means for predicting/preventing seizures and treating the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22168601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395327PMC
August 2021

Functional Gastrointestinal Disorders in Patients With Epilepsy: Reciprocal Influence and Impact on Seizure Occurrence.

Front Neurol 2021 6;12:705126. Epub 2021 Aug 6.

Epilepsy Unit, Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.

The complex relationship between the microbiota-gut-brain axis (MGBA) and epilepsy has been increasingly investigated in preclinical studies. Conversely, evidence from clinical studies is still scarce. In recent years, the pivotal role of MGBA dysregulation in the pathophysiology of functional gastrointestinal disorders (FGID) has been recognized. With this background, we aimed to investigate the prevalence of FGID in patients with epilepsy (PWE) and the possible impact of bowel movement abnormalities on seizure recurrence. A total of 120 PWE and 113 age-, sex-, and BMI-matched healthy subjects (HS) were consecutively enrolled. A questionnaire to evaluate the presence of FGID (according to Rome III diagnostic criteria) was administrated to all participants. In a subgroup of drug-resistant patients, we administered an questionnaire combining Bristol stool charts and seizure diaries to evaluate seizure trends and bowel movement changes. A higher prevalence of FGID in PWE (62.5%) than in HS (39.8%) was found ( < 0.001). The most frequently observed disorder was constipation, which was significantly higher in PWE than in HS (43.3 vs. 21.2%, < 0.001), and was not associated with anti-seizure medication intake according to multivariable analysis. In drug-resistant patients, most seizures occurred during periods of altered bowel movements, especially constipation. A significant weak negative correlation between the number of days with seizures and the number of days with normal bowel movements was observed ( = 0.04). According to multivariable logistic regression analysis, FGID was significantly associated with temporal lobe epilepsy as compared with other lobar localization ( = 0.03). Our clinical findings shed new light on the complex relationship between epilepsy and the MGBA, suggesting a bidirectional link between bowel movement abnormalities and seizure occurrence. However, larger studies are required to better address this important topic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.705126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377227PMC
August 2021

De novo DHDDS variants cause a neurodevelopmental and neurodegenerative disorder with myoclonus.

Brain 2021 Aug 11. Epub 2021 Aug 11.

Undiagnosed Diseases Program, National Institutes of Health, Bethesda, MD 20892-2152, USA.

Subcellular membrane systems are highly enriched in dolichol, whose role in organelle homeostasis and endosomal-lysosomal pathway remains largely unclear besides being involved in protein glycosylation. DHDDS encodes for the catalytic subunit (DHDDS) of the enzyme cis-prenyltransferase (cis-PTase), involved in dolichol biosynthesis and dolichol-dependent protein glycosylation in the endoplasmic reticulum. An autosomal recessive form of retinitis pigmentosa (retinitis pigmentosa 59) has been associated with a recurrent DHDDS variant. Moreover, two recurring de novo substitutions were detected in a few cases presenting with neurodevelopmental disorder, epilepsy, and movement disorder. We evaluated a large cohort of patients (n=25) with de novo pathogenic variants in DHDDS and provided the first systematic description of the clinical features and long-term outcome of this new neurodevelopmental and neurodegenerative disorder. The functional impact of the identified variants was explored by yeast complementation system and enzymatic assay. Patients presented during infancy or childhood with a variable association of neurodevelopmental disorder, generalized epilepsy, action myoclonus/cortical tremor, and ataxia. Later in the disease course they experienced a slow neurological decline with the emergence of hyperkinetic and/or hypokinetic movement disorder, cognitive deterioration, and psychiatric disturbances. Storage of lipidic material and altered lysosomes were detected in myelinated fibers and fibroblasts, suggesting a dysfunction of the lysosomal enzymatic scavenger machinery. Serum glycoprotein hypoglycosylation was not detected and, in contrast to retinitis pigmentosa and other congenital disorders of glycosylation involving dolichol metabolism, the urinary dolichol D18/D19 ratio was normal. Mapping the disease-causing variants into the protein structure revealed that most of them clustered around the active site of the DHDDS subunit. Functional studies using yeast complementation assay and in vitro activity measurements confirmed that these changes affected the catalytic activity of the cis-PTase and showed growth defect in yeast complementation system as compared with the wild-type enzyme and retinitis pigmentosa-associated protein. In conclusion, we characterized a distinctive neurodegenerative disorder due to de novo DHDDS variants, which clinically belongs to the spectrum of genetic progressive encephalopathies with myoclonus. Clinical and biochemical data from this cohort depicted a condition at the intersection of congenital disorders of glycosylation and inherited storage diseases with several features akin to of progressive myoclonus epilepsy such as neuronal ceroid lipofuscinosis and other lysosomal disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awab299DOI Listing
August 2021

Reconsidering the role of selective sodium channel blockers in genetic generalized epilepsy.

Acta Neurol Scand 2021 Jul 27. Epub 2021 Jul 27.

Epilepsy Unit, Department of Human Neurosciences, Policlinico Umberto I, Sapienza University of Rome, Italy.

Objective: Selective sodium channel blockers (SSCBs) have a limited use in genetic generalized epilepsy (GGE), due to their well-known risk of seizure worsening. Although their therapeutic potential in GGE has been suggested by recent evidence, electro-clinical data supporting their prescription are lacking. We aimed to investigate SSCB safety and effectiveness in a GGE cohort.

Methods: Subjects who received SSCBs and had ≥5-year follow-up were enrolled. Lamotrigine was excluded from analysis due to its broader pharmacodynamic spectrum and its better-documented efficacy in GGE.

Results: Fifty-six patients (median follow-up 28.5 years) were included. The most used SSCB was carbamazepine in 40 subjects. At the last medical observation, only 9 subjects were still receiving SSCBs. The occurrence of generalized polyspike-wave discharges (GPSWDs) predicted reduced SSCB retention in Cox multivariate analysis. A seizure reduction ≥50% occurred in 53.5% (30/56) of subjects when considering all seizure types; however, the proportion of responders increased to 67.9% when considering only generalized tonic-clonic seizures (GTCS). GPSWDs were significantly associated with a reduced response rate, whereas GGE with GTCS only syndrome with a better outcome. The switch from SSCBs to antiseizure medications licensed for GGE improved seizure control in 65% of patients. Seizure worsening was reported in 5/56 patients; juvenile myoclonic epilepsy and a family history of epilepsy were significantly associated with seizure aggravation.

Conclusion: SSCBs appeared effective on GTCS, but epilepsy aggravation and unsatisfactory control of other seizure types were not uncommon. Our study contributes to identifying new clinical and EEG variables associated with SSCB effectiveness and safety which may help neurologists in patients' management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ane.13509DOI Listing
July 2021

Differences in visual information processing style between Idiopathic Generalized Epilepsy with and without photosensitivity.

Epilepsy Behav 2021 09 9;122:108183. Epub 2021 Jul 9.

Department of Neurophysiology, Istituto Neurologico C. Besta, Milano, Italy.

Purpose: Recently, altered visual cortical processes i.e., lack of habituation to visual evoked potentials (VEP), has been highlighted in both photosensitive epilepsy and in a specific i.e., analytic mode of processing visual inputs. In this study we aimed at evaluating the relationship between photosensitivity (PS) and analytic style of processing visual information, in a sample of 30 patients with Idiopathic Generalized Epilepsy (IGE) and matched healthy controls.

Methods: At our Epilepsy unit of the Sapienza University of Rome, we consecutively enrolled 15 patients with IGE with PSand matched them with 15 patients with IGE without PS and 15 Healthy Volunteers. All patients underwent EEG recording in basal conditions during hyperventilation (3 Min), and intermittent light stimulation. The most effective frequencies comprised from 12 to 16 Hz. The instruments used to gather psychological cognitive behavioral data, consisted of participation in two tests: the Sternberg-Wagner Self-Assessment Inventory and the Mariani Learning Style Questionnaire.

Results: Compared to controls, both IGE groups show significantly higher scores for the analytic style (One-way ANOVA, F = 110.3, p < 0.0001). Epilepsy groups thereby showed very distinctive cognitive styles as measured with the Sternberg test. In the visual style, scores of the photosensitive Individuals with IGE were significantly higher than the non-photosensitive individuals with IGE (p < 0.0001, Tukey's post hoc test).

Conclusions: An association between analytic style of processing visual information and PS in IGE has been shown. The common neurophysiological features between these two factors, suggest the possibility to evaluate this cognitive behavior as a potential target for nonpharmacological therapeutic strategies in photosensitive epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2021.108183DOI Listing
September 2021

Clozapine-induced gastroesophageal rumination in 22q11.2 Deletion Syndrome. A case report on gastroesophageal side effects management without renouncing clozapine's effectiveness.

Clin Case Rep 2021 May 24;9(5):e04134. Epub 2021 May 24.

Department of Human Neurosciences Sapienza University Rome Italy.

Despite entailing more severe and uncommon side effects in 22q11.2DS compared to idiopathic schizophrenia, we strongly believe that clozapine should continue to be considered the gold standard for all treatment-resistant schizophrenia, even in 22qDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccr3.4134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142464PMC
May 2021

Letter to the editor: focal non-convulsive status epilepticus manifesting as utilization behavior.

Neurol Sci 2021 Sep 27;42(9):3885-3887. Epub 2021 May 27.

Epilepsy Unit, Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-021-05334-8DOI Listing
September 2021

Effects of antiseizure monotherapy on visuospatial memory in pediatric age.

Eur J Paediatr Neurol 2021 May 17;32:106-114. Epub 2021 Apr 17.

Child and Adolescent Neuropsychiatry Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy.

Introduction: Visuospatial abilities are fundamental for good school achievements and good daily functioning. Previous studies showed an impairment of visuospatial skills in pediatric patients with epilepsy; pharmacological treatment, although indispensable for the seizure control, could further affect cognitive functions. The aim of our study was to evaluate the visuospatial skills in children and adolescents with different forms of epilepsy well-controlled by antiseizure monotherapy, both at baseline and after one year follow-up, through a standardized neuropsychological assessment.

Methods: We recruited 207 children and adolescents (mean age = 10.35 ± 2.39 years) with epilepsy, well controlled by monotherapy with levetiracetam, valproic acid, ethosuximide, oxcarbazepine or carbamazepine and 45 age/sex-matched controls. All the participants performed the Rey-Osterrieth Complex Figure, a standardized test for visuospatial perception and visuospatial memory assessment, at baseline and after 12 month of drug therapy. Age, sex, executive functions, non-verbal intelligence, age at onset of epilepsy, epilepsy duration, epilepsy type, lobe and side of seizure onset were considered in our analysis. EEG, seizure frequency, and drug dose were also recorded.

Results: At baseline, the epilepsy group performed significantly worse than controls in the Immediate Recall test but not the Direct Copy test, without differences between epilepsy subgroups. Immediate Recall scores were related to age of seizure onset and epilepsy duration and executive functions. The re-assessment after 1 year showed that the Immediate Recall mean scores were not significantly changed in the levetiracetam and oxcarbazepine group, while they significantly worsened in the valproic acid, ethosuximide and carbamazepine groups. The Immediate Recall scores were correlated to age, age at onset of epilepsy, epilepsy duration, and executive functions.

Conclusions: Children with epilepsy may exhibit visuospatial memory impairment compared to their peer, that may be correlated to some features of the epilepsy itself and to the impairment of executive functions. Different antiseizure medications can affect visuospatial memory differently, so it is important monitoring this aspect in pediatric patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpn.2021.04.004DOI Listing
May 2021

Progressive myoclonus epilepsies-Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes.

Am J Hum Genet 2021 04;108(4):722-738

Neurology - Neurophysiology Unit, ASST dei Sette Laghi, Galmarini Tradate Hospital, Tradate 21049, Italy.

Progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous rare diseases. Over 70% of PME cases can now be molecularly solved. Known PME genes encode a variety of proteins, many involved in lysosomal and endosomal function. We performed whole-exome sequencing (WES) in 84 (78 unrelated) unsolved PME-affected individuals, with or without additional family members, to discover novel causes. We identified likely disease-causing variants in 24 out of 78 (31%) unrelated individuals, despite previous genetic analyses. The diagnostic yield was significantly higher for individuals studied as trios or families (14/28) versus singletons (10/50) (OR = 3.9, p value = 0.01, Fisher's exact test). The 24 likely solved cases of PME involved 18 genes. First, we found and functionally validated five heterozygous variants in NUS1 and DHDDS and a homozygous variant in ALG10, with no previous disease associations. All three genes are involved in dolichol-dependent protein glycosylation, a pathway not previously implicated in PME. Second, we independently validate SEMA6B as a dominant PME gene in two unrelated individuals. Third, in five families, we identified variants in established PME genes; three with intronic or copy-number changes (CLN6, GBA, NEU1) and two very rare causes (ASAH1, CERS1). Fourth, we found a group of genes usually associated with developmental and epileptic encephalopathies, but here, remarkably, presenting as PME, with or without prior developmental delay. Our systematic analysis of these cases suggests that the small residuum of unsolved cases will most likely be a collection of very rare, genetically heterogeneous etiologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2021.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059372PMC
April 2021

Acute-onset binocular diplopia in neurological unit: Aetiological factors and diagnostic assessment.

Acta Neurol Scand 2021 Jul 31;144(1):92-98. Epub 2021 Mar 31.

Department of Human Neurosciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.

Objectives: To investigate the aetiology of acute-onset binocular diplopia (AOBD) in neurological units and identify the key diagnostic procedures in this setting.

Materials And Methods: Clinico-demographic data from patients hospitalized for AOBD from 2008 to 2019 were retrospectively reviewed. AOBD due to an underlying neurological disorder known to cause diplopia was addressed as secondary diplopia. Ophthalmoparesis plus was defined when subtle neurological signs/symptoms other than ophthalmoparesis were detected during neurological examination.

Results: A total of 171 patients (mean age 57.6 years) were included in the study. A total of 89 subjects (52%) had an oculomotor disturbance consistent with sixth nerve palsy, and 42 (24.6%) showed multiple oculomotor nerve involvement. The most common cause of AOBD was presumed to be microvascular in 56 patients (32.7%), while a secondary aetiology was identified in 102 (59.6%). Ophthalmoparesis plus and multiple oculomotor nerve involvement significantly predicted a secondary aetiology in multivariable logistic regression analysis. Brain CT was never diagnostic in isolated ophthalmoparesis. A combination of neuroimaging examinations established AOBD diagnosis in 54.9% of subjects, whereas rachicentesis and neurophysiological examinations were found to be performant in the remaining cases.

Conclusions: AOBD may herald insidious neurological disease, and an extensive diagnostic workup is often needed to establish a diagnosis. Neurological examination was pivotal in identifying patients at higher risk of secondary aetiology. Even in cases of apparently benign presentation, a serious underlying disease cannot be excluded. Brain MRI was found to perform well in all clinical scenarios, and it should be always considered when managing AOBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ane.13425DOI Listing
July 2021

Water drinking behavior: a clinical clue for the diagnosis of limbic encephalitis in an elderly patient.

Acta Neurol Belg 2021 Aug 8;121(4):1073-1075. Epub 2021 Mar 8.

Department of Human Neurosciences, "Sapienza" University of Rome, Viale dell'Università 30, 00185, Rome, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13760-021-01633-1DOI Listing
August 2021

Appropriate use of generic and branded antiseizure medications in epilepsy: Updated recommendations from the Italian League Against Epilepsy (LICE).

Epilepsy Behav 2021 03 10;116:107804. Epub 2021 Feb 10.

Science of Health Department, School of Medicine, University of Catanzaro, Italy. Electronic address:

Generic drugs are increasingly used to treat many diseases including epilepsy. The growing importance of generic antiseizure medications (ASMs) has led the ASMs commission of the Italian League Against Epilepsy (LICE) to review current evidence in the literature about efficacy and safety of these products. Recommendations from other scientific organizations have also been considered to provide an update of the LICE position about their utilization (List of Recommendations). Compared with the previous literature review, randomized controlled trials assessing bioequivalence among branded drugs and generics are currently available. Although some contrasting results have been reported, brand-to-generic switching was effective and tolerable in real-life settings, with similar adverse event ratios. Based on these findings, LICE concluded that, conforming to the rigorous regulation of USA and EU markets, generic ASMs are not inferior to the respective branded, providing a cost advantage for patients starting or replacing monotherapy or add-on, and for those with incomplete seizure control. Branded-to-generic (and vice versa) switching is not recommended (although applicable) during seizure remission, as well as the generic-to-other generic switching. Other recommendations focus on the appropriateness of therapeutic drug monitoring (TDM) when switching is required, paying attention to avoiding the erroneous switch between modified and immediate-release formulations during dispensation. Finally, to support patients' compliance, they should be assured of generics' safety and efficacy and carefully informed with practical advice, particularly when the switching is associated with aspect modifications (e.g. color and shape changes) of the pill or the packaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2021.107804DOI Listing
March 2021

Persistent treatment resistance in genetic generalized epilepsy: A long-term outcome study in a tertiary epilepsy center.

Epilepsia 2020 11 14;61(11):2452-2460. Epub 2020 Oct 14.

Epilepsy Unit, Department of Human Neurosciences, Policlinico "Umberto I", "Sapienza" University, Rome, Italy.

Objective: To assess prognostic patterns and investigate clinical and electroencephalography (EEG) variables associated with persistent treatment resistance in a population of genetic generalized epilepsy (GGE) patients with a long-term follow-up.

Methods: Data from GGE patients followed from 1975 to 2019 were reviewed retrospectively. Subjects with a follow-up >10 years, starting from epilepsy diagnosis, were included. Persistent treatment resistance was defined as the absence of any period of remission ≥1 year despite treatment with two appropriate and adequate antiepileptic drugs (AEDs).

Results: One hundred ninety-nine patients were included. The median age was 39.5 years (interquartile range [IQR] 30-49) and the median follow-up was 27 years (IQR 18-35). The most common syndrome was juvenile myoclonic epilepsy (JME), diagnosed in 44.2% of patients. During follow-up, 163 subjects (81.9%) experienced 3-year remission from any seizure type, whereas 5- and 10-year remission occurred in 141 (70.8%) and 92 (46.2%) cases, respectively. The most common prognostic pattern was a relapsing-remitting course, observed in 80 patients (40.2%), whereas 29 (14.6%) displayed persistent treatment resistance. According to multivariable logistic regression analysis, febrile seizures (FS), specific EEG patterns (namely generalized paroxysmal fast activity, GPFA) and valproate (VPA) resistance were the only variables significantly associated with persistent treatment resistance. JME was the only epilepsy syndrome statistically associated with persistent treatment resistance in univariable logistic regression analysis.

Significance: Persistent treatment resistance was observed in almost 15% of GGE patients followed in a tertiary epilepsy center. A worse outcome was associated with specific clinical variables (JME, FS) and EEG patterns (GPFA).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.16708DOI Listing
November 2020

Clinical and Kinematic Features of Valproate-Induced Tremor and Differences with Essential Tremor.

Cerebellum 2021 Jun 16;20(3):374-383. Epub 2020 Nov 16.

IRCCS Neuromed, Pozzilli (IS), Italy.

Tremor is a common movement disorder that can be induced by medications, including valproate, which is used for the treatment of epilepsy. However, the clinical and neurophysiological features of valproate-induced tremor are still under-investigated. We performed a clinical and kinematic assessment of valproate-induced tremor by considering tremor body distribution and activation conditions. We investigated possible correlations between demographic and clinical data and kinematic features. Valproate-induced tremor results were also compared with those collected in a large sample of patients with essential tremor. Sixteen valproate-induced tremor patients and 93 essential tremor patients were enrolled. All participants underwent a standardised neurological examination and video recording. Patients also underwent an objective assessment of postural, kinetic and rest tremor of the upper limbs and head tremor through kinematic analysis. Nonparametric tests were used for statistical comparisons between the two groups. Clinical evaluation showed a higher occurrence of rest tremor as well as head or voice, and lower limb involvement in patients with valproate-induced tremor. Kinematic analysis showed a substantial variability in the tremor features of patients with valproate-induced tremor. Compared to essential tremor, we found a higher occurrence of rest tremor of the upper limbs and the involvement of more body segments in valproate-induced tremor patients. Valproate-induced tremor has distinctive clinical and kinematic features, which may suggest that valproate interferes with the cerebellar functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12311-020-01216-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213593PMC
June 2021

Abnormalities of Cortical Sources of Resting State Delta Electroencephalographic Rhythms Are Related to Epileptiform Activity in Patients With Amnesic Mild Cognitive Impairment Not Due to Alzheimer's Disease.

Front Neurol 2020 23;11:514136. Epub 2020 Oct 23.

Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy.

In the present exploratory and retrospective study, we hypothesized that cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms might be more abnormal in patients with epileptiform EEG activity (spike-sharp wave discharges, giant spikes) and amnesic mild cognitive impairment not due to Alzheimer's disease (noADMCI-EEA) than matched noADMCI patients without EEA (noADMCI-noEEA). Clinical, neuroimaging, neuropsychological, and rsEEG data in 32 noADMCI and 30 normal elderly (Nold) subjects were available in a national archive. Age, gender, and education were carefully matched among them. No subject had received a clinical diagnosis of epilepsy. Individual alpha frequency peak (IAF) was used to determine the delta, theta, and alpha frequency bands of rsEEG rhythms. Fixed beta and gamma bands were also considered. Regional rsEEG cortical sources were estimated by eLORETA freeware. Area under receiver operating characteristic (AUROC) curves indexed the accuracy of eLORETA solutions in the classification between noADMCI-EEA and noADMCI-noEEA individuals. As novel findings, EEA was observed in 41% of noADMCI patients. Furthermore, these noADMCI-EEA patients showed higher temporal delta source activities as compared to noADMCI-no EEA patients and Nold subjects. Those activities discriminated individuals of the two NoADMCI groups with an accuracy of about 70%. The significant percentage of noADMCI-EEA patients showing EEA and marked abnormalities in temporal rsEEG rhythms at delta frequencies suggest a substantial role of underlying neural hypersynchronization mechanisms in their brain dysfunctions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.514136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644902PMC
October 2020

Seizures in autoimmune encephalitis: Findings from an EEG pooled analysis.

Seizure 2020 Dec 31;83:160-168. Epub 2020 Oct 31.

Epilepsy Unit, Department of Human Neurosciences, "Sapienza" University of Rome, Rome, Italy. Electronic address:

Purpose: Seizures are common in autoimmune encephalitis (AE), and an extensive work-up is required to exclude alternative etiologies. The aim of our study was to identify possible clinical/EEG peculiarities suggesting the immune-mediated origin of late-onset seizures.

Methods: Thirty patients diagnosed with AE (19 men, median age 68 years, 18 seronegative) were included. Overall 212 video-electroencephalographic (EEG) and 31 24-h ambulatory EEG (AEEG) recordings were retrospectively reviewed. Posterior dominant rhythm, interictal epileptiform discharges (IEDs), clinical (CSs) and subclinical seizures (SCSs) were analyzed.

Results: Six-hundred-nineteen ictal events were recorded in 19/30 subjects, mostly (568/619) during AE acute stage. Among ten patients with CSs other than faciobrachial dystonic seizures, 7 showed prominent autonomic and emotional manifestations. SCSs were detected in 11 subjects, mainly via AEEG (260/287 SCSs vs 150/332 CSs, p < 0.001). Eight patients presented seizures during hyperventilation. IEDs, documented in 21 cases, were bilateral in 14 and focal temporal in 13. Multiple ictal EEG patterns were detected in 9/19 patients, 6 of whom had both CSs and SCSs, bilateral asynchronous seizures and ictal activities arising from temporal and extra-temporal regions. No correlation was found between the lateralization of MRI alterations and that of EEG findings.

Conclusion: Our study confirms that adult-onset, high frequency focal seizures with prominent autonomic and emotional manifestations should be investigated for AE. Multiple ictal EEG patterns could represent a 'red flag', reflecting a widespread neuronal excitability related to the underlying immune-mediated process. Finally, our work enhances the crucial role of long-lasting EEG monitoring in revealing subclinical and relapsing seizures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2020.10.019DOI Listing
December 2020

The potential impact of enhanced hygienic measures during the COVID-19 outbreak on hospital-acquired infections: A pragmatic study in neurological units.

J Neurol Sci 2020 11 29;418:117111. Epub 2020 Aug 29.

Department of Human Neurosciences, Policlinico Umberto I, Sapienza University of Rome, Italy. Electronic address:

Objective: Hospital-acquired infections (HAIs) are frequent complications among acute patients hospitalized in neurological units, especially among those hospitalized for stroke. This study aimed to investigate if enhanced hygienic measures, including the systematic use of personal protective equipment (PPE), determined a decrease in HAI during the recent COVID-19 outbreak in "COVID-free" neurological units.

Methods: Patients hospitalized in neurology and stroke units of Policlinico Umberto I Hospital in Rome from March 8, 2020 and discharged prior to May 31, 2020 were included in the study and compared with patients hospitalized during the same period in 2019.

Results: A total of 319 patients were included in the study (n = 103 in 2020, n = 216 in 2019). Among patients hospitalized in 2019, the incidence of HAIs was 31.5% (95% confidence interval (CI): 0.25-0.38), compared with 23.3% (95% CI: 0.15-0.32) in 2020 (p = 0.12). Multivariable logistic regression showed that hospitalization during 2020 was independently associated with a lower risk of HAIs (odds ratio: 0.34, 95% CI:0.16-0.71, p = 0.004). Poisson regression models showed that hospitalization during 2020 was also independently associated with both a lower number of HAIs (relative risk [RR]: 0.56, 95% CI:0.38-0.81, p = 0.01) and a lower number of prescribed antibiotics per patient (RR: 0.66, 95% CI: 0.49-0.87, p = 0.02).

Conclusion: Our study design provides evidence regarding the impact of stricter hygienic measures, such as increased PPE use, on HAIs. Larger studies are needed to support the extension of preventive measures even after the COVID-19 outbreak in order to limit the occurrence of HAIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2020.117111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833504PMC
November 2020

Pharmacokinetic considerations about antiseizure medications in the elderly.

Expert Opin Drug Metab Toxicol 2020 Oct 25;16(10):983-995. Epub 2020 Sep 25.

Science of Health Department, School of Medicine, University of Catanzaro, Italy.

Introduction: Epilepsy represents the third most common neurological disorder in the elderly. Antiseizure medications (ASMs) are often used not only to treat epilepsy but also other disorders in this age group. Many physio-pathological changes occur in body composition and organ or system functions with aging. Furthermore, drug-drug interactions (DDIs) represent a major risk considering the prevalence of polytherapy in the elderly.

Areas Covered: Relevant studies on the pharmacokinetics of ASMs in the elderly were identified through a literature search. We have reviewed all available data on known alterations in pharmacokinetic parameters of ASMs in elderly also considering pathophysiological alterations such as renal function impairment. Finally, we have highlighted the potential risk of DDIs with some drug classes.

Expert Opinion: Large interindividual variability also due to co-morbidities and related co-therapies makes elderly patients a not homogeneous group. Overall, a reduction in loading and maintenance doses of almost all ASMs should be considered to avoid adverse events (AEs) as well as a slow titration, following the rule 'start low and go slow'. Therapeutic drug monitoring should be performed to apply the 'individual therapeutic concentration' and implemented to overcome the age-related differences between dose and plasma concentrations, to monitor DDIs and guide dosage adjustments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17425255.2020.1806236DOI Listing
October 2020

Social cognition and executive functions in children and adolescents with focal epilepsy.

Eur J Paediatr Neurol 2020 Sep 13;28:167-175. Epub 2020 Jul 13.

Department of Psychological, Pedagogical and Educational Sciences, University of Palermo, Palermo, Italy.

Objectives: Deficits in facial emotion recognition and Theory of Mind are frequent in patients with epilepsy. Although this evidence, studies on pediatric age are few and the relation between these abilities and other cognitive domain remains to be better elucidated. The purpose of our study is to evaluate facial emotion recognition and Theory of Mind in children and adolescents with focal epilepsy, and correlate them with intelligence and executive functions.

Materials And Methods: Our work is a cross-sectional observational study. Sixty-two children and adolescents aged between 7-16 years diagnosed by focal epilepsy and 32 sex/age-matched controls were recruited. All participants were administered a standardized battery tests to assess social cognition (NEPSY-II), executive functions (EpiTrack Junior) and cognitive non-verbal level (Raven Progressive Matrices).

Results: Emotion recognition mean score was significantly lower in the epilepsy group than in the controls to Student's t-test (p<0.05). Epilepsy group showed an impairment in happiness, sadness, anger and fear recognition, compared to controls (p<0.05). Theory of Mind mean score was also significantly lower in epilepsy group than controls (p<0.05). Deficits in emotion recognition seemed to be related to low age at onset of epilepsy, long duration of disease, low executive functions and low non-verbal intelligence. Deficits in Theory of Mind seemed to be related to a high seizure frequency.

Conclusions: Our results suggest that children and adolescents with focal epilepsy had deficit in facial emotion recognition and Theory of Mind, compared to their peer. Both these difficulties seem to be related to some features of epilepsy itself. Our results also suggest that deficits in facial emotion recognition are potentially related to difficulties in executive functions and non-verbal intelligence. More studies are needed to confirm these hypotheses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpn.2020.06.019DOI Listing
September 2020

Ictal Asystole in Drug-Resistant Focal Epilepsy: Two Decades of Experience from an Epilepsy Monitoring Unit.

Brain Sci 2020 Jul 12;10(7). Epub 2020 Jul 12.

IRCCS NEUROMED, 86077 Pozzilli (IS), Italy.

Background: Ictal asystole (IA) is a rare event observed in people with epilepsy (PwE). Clinical and IA video-electroencephalographic findings may be helpful in screening for high-risk subjects. From all PwE undergoing video-EEG for presurgical evaluation between 2000 and 2019, we retrospectively selected those with at least one IA (R-R interval of ≥3 s during a seizure). IA was detected in eight out of 1088 (0.73%) subjects (mean age: 30 years; mean epilepsy duration: 9.6 years). Four out of them had a history of atonic falls. No patients had cardiac risk factors or cardiovascular diseases. Seizure onset was temporal ( = 5), temporo-parietal ( = 1) or frontal ( = 2), left-sided and right-sided in five and two patients, respectively. In one case a bilateral temporal independent seizure onset was recorded. IA was recorded in 11 out of 18 seizures. Mean IA duration was 13 s while mean IA latency from seizure onset was 26.7 s. Symptoms related to IA were observed in all seizures. IA is a rare and self-limiting event often observed during video-EG in patients with a history of atonic loss of consciousness and/or tardive falls in the course of a typical seizure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci10070443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408581PMC
July 2020

Post-Traumatic Meningitis Is a Diagnostic Challenging Time: A Systematic Review Focusing on Clinical and Pathological Features.

Int J Mol Sci 2020 Jun 10;21(11). Epub 2020 Jun 10.

Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome (RM), Italy.

Post-traumatic meningitis is a dreadful condition that presents additional challenges, in terms of both diagnosis and management, when compared with community-acquired cases. Post-traumatic meningitis refers to a meningeal infection causally related to a cranio-cerebral trauma, regardless of temporal proximity. The PICO (participants, intervention, control, and outcomes) question was as follows: "Is there an association between traumatic brain injury and post-traumatic meningitis?" The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. Studies examining post-traumatic meningitis, paying particular attention to victims of traumatic brain injury, were included. Post-traumatic meningitis represents a high mortality disease. Diagnosis may be difficult both because clinical signs are nonspecific and blurred and because of the lack of pathognomonic laboratory markers. Moreover, these markers increase with a rather long latency, thus not allowing a prompt diagnosis, which could improve patients' outcome. Among all the detectable clinical signs, the appearance of cranial cerebrospinal fluid (CSF) leakage (manifesting as rhinorrhea or otorrhea) should always arouse suspicion of meningitis. On one hand, microbiological exams on cerebrospinal fluid (CSF), which represent the gold standard for the diagnosis, require days to get reliable results. On the other hand, radiological exams, especially CT of the brain, could represent an alternative for early diagnosis. An update on these issues is certainly of interest to focus on possible predictors of survival and useful tools for prompt diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21114148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312088PMC
June 2020

Valproate impact and sex-dependent seizure remission in patients with idiopathic generalized epilepsy.

J Neurol Sci 2020 08 30;415:116940. Epub 2020 May 30.

Epilepsy Unit, Department of Human Neurosciences, Policlinico Umberto I, "Sapienza" University, Rome, Italy. Electronic address:

Background: Idiopathic Generalized Epilepsy (IGE) management has become increasingly challenging due to the restricted use of Valproate (VPA) in females. The aim of the study was to assess possible differences in terms of seizure outcome between men and women suffering from IGE.

Methods: A cohort of IGE patients (age range: 13-50 years) followed from 1980 to 2018 were included. Their medical history was retrospectively reviewed to investigate possible factors influencing seizure outcome. Seizure Remission (SR) was defined as the absence of any seizure type over 18 months prior to the last medical observation. The primary outcome was to evaluate sex differences in terms of SR at last observation. A multivariable logistic regression model was elaborated using SR as dependent variable.

Results: Three-hundred and sixty patients were included, 204 (56.7%) of whom were women. The median age at the end of follow-up was 30. At last medical observation, fewer women were receiving VPA compared with men (females 39.7% vs males 79.5%, p < .001). Overall SR was 70.6%. SR was significantly different according to sex (females 62.3% vs males 81.4%, p < .001). Multivariable logistic regression model showed that female sex (Odds Ratios [OR] = 0.52, 95% Confidence Interval [CI] = 0.29-0.94; p = .03), VPA treatment at last observation (OR = 0.44, 95% CI = 0.25-0.76; p = .003) and epilepsy syndrome (p < .001) were the factors independently associated with SR.

Conclusions: Recent modifications in VPA prescribing patterns may have determined a worse seizure control among IGE female patients. Comparative clinical trials assessing the best therapeutic options for women with childbearing potential are urgently needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2020.116940DOI Listing
August 2020

Antidepressant effect of vagal nerve stimulation in epilepsy patients: a systematic review.

Neurol Sci 2020 Nov 10;41(11):3075-3084. Epub 2020 Jun 10.

Institute of Neurology, University Magna Graecia, Germaneto (CZ), Italy.

Background: Vagal nerve stimulation (VNS) is an effective palliative therapy in drug-resistant epileptic patients and is also approved as a therapy for treatment-resistant depression. Depression is a frequent comorbidity in epilepsy and it affects the quality of life of patients more than the seizure frequency itself. The aim of this systematic review is to analyze the available literature about the VNS effect on depressive symptoms in epileptic patients.

Material And Methods: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to January 2020. All studies concerning depressive symptom assessment in epileptic patients treated with VNS were included.

Results: Nine studies were included because they fulfilled inclusion criteria. Six out of nine papers reported a positive effect of VNS on depressive symptoms. Eight out of nine studies did not find any correlation between seizure reduction and depressive symptom amelioration, as induced by VNS. Clinical scales for depression, drug regimens, and age of patients were broadly different among the examined studies.

Conclusions: Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. However, more rigorous studies addressing this issue are encouraged.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-020-04479-2DOI Listing
November 2020

Faciobrachial Dystonic Seizures: The Borderland Between Epilepsy and Movement Disorders.

Mov Disord Clin Pract 2020 Feb 8;7(2):228-229. Epub 2020 Jan 8.

Epilepsy Unit, Department of Human Neurosciences "Sapienza" University Rome Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mdc3.12884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011829PMC
February 2020

An uncommon case of thunderclap headache in a patient with Marfan syndrome.

Acta Neurol Belg 2021 Oct 4;121(5):1361-1363. Epub 2020 May 4.

Department of Human Neurosciences, Policlinico "Umberto I", Sapienza University of Rome, Viale dell'Università, 30, 00185, Rome, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13760-020-01364-9DOI Listing
October 2021
-->