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OBJECTIVE: Women of childbearing age with juvenile absence epilepsy (JAE) face treatment challenges due to limited access to safe and effective anti-seizure medications (ASMs). In a previous study we compared the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) in women with idiopathic generalized epilepsy (IGE), highlighting a superiority of LEV in juvenile myoclonic epilepsy. In this study, we specifically reanalyzed, through a Bayesian approach and by expanding the previously published cohort, the comparative effectiveness of these ASMs as initial monotherapy in JAE. METHODS: We conducted a multicenter, retrospective, comparative effectiveness study on women of childbearing age diagnosed with JAE and prescribed LEV or LTG as the initial ASM. Inverse probability treatment weighting (IPTW) Bayesian Cox proportional hazard models were employed to evaluate treatment failure (TF) due to ineffectiveness and ASM retention. The patients' center of provenance and year of prescription were considered as random effect factors. Posterior probabilities and relative log-risk distribution were computed, and the distribution of posterior draws was analyzed to assess the evidence supporting LTG superiority over LEV. RESULTS: Of 123 patients, those treated with LTG (n = 67) demonstrated lower TF and higher ASM retention than those treated with LEV (n = 56), with the IPTW-weighted Bayesian Cox proportional hazards model showing a 99.2% posterior probability of LTG being superior on TF and a 99.5% probability on ASM retention. Additional analyses on ≥50% and ≥75% seizure reduction through IPTW-weighted Bayesian logistic regression largely confirmed these findings, whereas the two ASMs did not show evident differences in terms of seizure freedom. The two ASMs showed comparable safety profiles, with only a minority of patients discontinuing treatment due to side effects. SIGNIFICANCE: Bayesian reanalysis supports LTG as first-line monotherapy for JAE in women of childbearing age, emphasizing the importance of individualized treatment strategies in women with IGE. This study underscores the value of Bayesian methods in refining clinical research and treatment decisions.
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Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE). A total of 336 participants were included, of whom 24 (7.1%) received TPM and 312 (92.9%) LEV. Women treated with TPM had significantly higher risks of treatment failure and treatment withdrawal and were less likely to achieve seizure freedom at 12 months compared to women treated with LEV. In conclusion, this study highlighted a low tendency among clinicians to use TPM in women of childbearing potential with IGE, anticipating the recently released restrictions on its use. Furthermore, the available data on effectiveness do not appear to support the use of TPM in this population.
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Epilepsia Generalizada , Epilepsia , Embarazo , Humanos , Femenino , Topiramato/efectos adversos , Anticonvulsivantes/efectos adversos , Teratógenos/toxicidad , Estudios Retrospectivos , Estudios de Cohortes , Fructosa/uso terapéutico , Epilepsia/tratamiento farmacológico , Epilepsia Generalizada/tratamiento farmacológico , Levetiracetam/efectos adversos , Inmunoglobulina E/uso terapéuticoRESUMEN
OBJECTIVE: There are few comparative data on the third-generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives. METHODS: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add-on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan-Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models. RESULTS: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)-naïve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.29) and PER groups (HR = 1.64, 95% CI = 1.06-2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71-16.61), as well as PER-treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05-2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] = .08, 95% CI = .01-.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV-naïve (OR = 10.32, 95% CI = 1.55-68.78) versus men. PER (OR = 6.93, 95% CI = 3.32-14.44) and BRV in LEV-naïve patients (OR = 6.80, 95% CI = 2.64-17.52) had a higher chance of AEs than LCM. SIGNIFICANCE: Comparative evidence from real-world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics.
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Epilepsias Parciales , Epilepsia , Nitrilos , Piridonas , Masculino , Adulto , Humanos , Femenino , Anticonvulsivantes/efectos adversos , Epilepsias Parciales/tratamiento farmacológico , Estudios Retrospectivos , Levetiracetam/uso terapéutico , Lacosamida/uso terapéutico , Epilepsia/tratamiento farmacológico , Pirrolidinonas/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: High-density EEG (hdEEG) is a validated tool in presurgical evaluation of people with epilepsy. The aim of this national survey is to estimate diffusion and knowledge of hdEEG to develop a network among Italian epilepsy centers. METHODS: A survey of 16 items (and 15 additional items) was distributed nationwide by email to all members of the Italian League Against Epilepsy and the Italian Society of Clinical Neurophysiology. The data obtained were analyzed using descriptive statistics. RESULTS: A total of 104 respondents were collected from 85 centers, 82% from the Centre-North of Italy; 27% of the respondents had a hdEEG. The main applications were for epileptogenic focus characterization in the pre-surgical evaluation (35%), biomarker research (35%) and scientific activity (30%). The greatest obstacles to hdEEG were economic resources (35%), acquisition of dedicated personnel (30%) and finding expertise (17%). Dissemination was limited by difficulties in finding expertise and dedicated personnel (74%) more than buying devices (9%); 43% of the respondents have already published hdEEG data, and 91% of centers were available to participate in multicenter hdEEG studies, helping in both pre-processing and analysis. Eighty-nine percent of respondents would be interested in referring patients to centers with established experience for clinical and research purposes. CONCLUSIONS: In Italy, hdEEG is mainly used in third-level epilepsy centers for research and clinical purposes. HdEEG diffusion is limited not only by costs but also by lack of trained personnel. Italian centers demonstrated a high interest in educational initiatives on hdEEG as well as in clinical and research collaborations.
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Epilepsia , Humanos , Electroencefalografía , Epilepsia/diagnóstico , Italia , Encuestas y CuestionariosRESUMEN
PURPOSE: To establish whether a slow or a rapid withdrawal of antiepileptic monotherapy influences relapse rate in seizure-free adults with epilepsy and calculates compliance and differences in the severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries, and death. METHODS: This is a multicentre, prospective, randomized, open label, non-inferiority trial in people aged 16 + years who were seizure-free for more than 2 years. Patients were randomized to slow withdrawal (160 days) or rapid withdrawal (60 days) and were followed for 12 months. The primary outcome was the probability of a first seizure relapse within the 12-months follow-up. The secondary outcomes included the cumulative probability of relapse at 3, 6, 9, and 12 months. A non-inferiority analysis was performed with non-inferiority margin of - 0.15 for the difference between the probabilities of seizure recurrence in slow versus rapid withdrawal. RESULTS: The sample comprised 48 patients, 25 randomized to slow withdrawal and 23 to rapid withdrawal. Median follow-up was 11.9 months. In the intention-to-treat population, 3 patients in the slow-withdrawal group and 1 in the rapid withdrawal group experienced seizure relapses. The corresponding probabilities of seizure recurrence were 0.12 for slow withdrawal and 0.04 for rapid withdrawal, giving a difference of 0.08 (95% CI - 0.12; 0.27), which is entirely above the non-inferiority margin. No patients developed status epilepticus and seizure-related injuries or died. Risks were similar in the Per-Protocol population. CONCLUSIONS: Seizure-relapse rate after drug discontinuation is lower than in other reports, without complications and unrelated to the duration of tapering.
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Epilepsia , Estado Epiléptico , Adulto , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Prospectivos , Recurrencia , Convulsiones/tratamiento farmacológico , Estado Epiléptico/tratamiento farmacológicoRESUMEN
Cognition was assessed in hepatitis C virus (HCV) patients, who did not meet the criteria for a minimal hepatic encephalopathy. Their liver function was compensated. We then disentangled potential cognitive changes associated with a sustained virologic response at 12 weeks (SVR-12), following treatment with direct antiviral agents (DAAs). We studied 23 selected HCV patients with a battery of standard neuropsychological tests, and with recordings of the P300 wave, a cerebral potential of "cognitive" significance. There was a baseline evaluation (T0) and a second one 6 months later (T1). We had 2 control groups of comparable age and sex, i.e., 15 patients suffering from non-alcoholic fatty liver disease (NAFLD) and 15 healthy subjects. At T0, we detected a significant (p < 0.05) cognitive impairment in the HCV group, which involved episodic and working memory, attention, visuospatial and verbal abilities, executive functions, and logic reasoning. The P300 latency was significantly (p < 0.05) delayed in the group. At T1, we observed some significant (p < 0.05) HCV recovery in given test domains, e.g., memory, executive functions, and reasoning. Accordingly, the P300 latency shortened significantly (p < 0.05). HCV patients exhibited subtle cognitive defects, somehow independent of their liver condition, possibly linked to direct or indirect brain involvement by the virus. These defects partly recovered following the SVR-12, as achieved through DAAs. The P300 wave was a valid neurophysiologic counterpart of these changes. DAAs can have a role in the early preservation of cognition in HCVs.
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Antivirales/uso terapéutico , Encéfalo/virología , Disfunción Cognitiva/diagnóstico , Hepatitis C Crónica/diagnóstico , Hígado/virología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Anciano , Atención/efectos de los fármacos , Atención/fisiología , Encéfalo/efectos de los fármacos , Estudios de Casos y Controles , Cognición/efectos de los fármacos , Cognición/fisiología , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/psicología , Disfunción Cognitiva/virología , Potenciales Relacionados con Evento P300/efectos de los fármacos , Potenciales Relacionados con Evento P300/fisiología , Función Ejecutiva/efectos de los fármacos , Función Ejecutiva/fisiología , Femenino , Hepacivirus/efectos de los fármacos , Hepacivirus/patogenicidad , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/psicología , Hepatitis C Crónica/virología , Humanos , Hígado/efectos de los fármacos , Masculino , Memoria a Corto Plazo/efectos de los fármacos , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad del Hígado Graso no Alcohólico/psicología , Enfermedad del Hígado Graso no Alcohólico/virología , Respuesta Virológica SostenidaRESUMEN
The major link between the visual and motor systems is via the dorsal stream pathways from visual to parietal and frontal areas of the cortex. Although the pathway appears to be indirect, there is evidence that visual input can reach the motor cortex at relatively short latency. To shed some light on its neural basis, we studied the visuomotor interaction using paired transcranial magnetic stimulation (TMS). Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous in sixteen healthy volunteers. A conditioning stimulus (CS) was applied over the phosphene hotspot of the visual cortex, followed by a test stimulus over the left primary motor cortex (M1) with a random interstimulus interval (ISI) in range 12-40 ms. The effects of paired stimulation were retested during visual and auditory reaction-time tasks (RT). Finally, we measured the effects of a CS on short-interval intracortical inhibition (SICI). At rest, a CS over the occiput significantly (P < 0.001) suppressed test MEPs with an ISI in the range 18-40 ms. In the visual RT, inhibition with an ISI of 40 ms (but not 18 ms) was replaced by a time-specific facilitation (P < 0.001), whereas, in the auditory RT, the CS no longer had any effect on MEPs. Finally, an occipital CS facilitated SICI with an ISI of 40 ms (P < 0.01). We conclude that it is possible to study separate functional connections from visual to motor cortices using paired-TMS with an ISI in the range 18-40 ms. The connections are inhibitory at rest and possibly mediated by inhibitory interneurones in the motor cortex. The effect with an ISI of 40 ms reverses into facilitation during a visuomotor RT but not an audiomotor RT. This suggests that it plays a role in visuomotor integration.
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Corteza Motora/fisiología , Estimulación Magnética Transcraneal , Corteza Visual/fisiología , Adulto , Electroencefalografía , Potenciales Evocados Auditivos/fisiología , Potenciales Evocados Motores/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción/fisiologíaRESUMEN
OBJECTIVE: The photoparoxysmal response (PPR) involves rapid spread of epileptic activity from visual to parietal and frontal areas. We used a transcranial magnetic stimulation (TMS) technique to assess the physiologic connections between primary visual (V1) and motor (M1) areas in patients with idiopathic generalized epilepsy (IGE). We hypothesized that in PPR-positive patients, M1 would respond excessively to inputs from V1. METHODS: Eleven photosensitive patients with IGE who had a PPR at the time of the study were compared with 10 similar patients without a PPR, and with 11 healthy subjects of similar age and sex. The connection between V1 and M1 was assessed in resting participants by delivering a conditioning stimulus (CS) over the phosphene hotspot of the visual cortex (intensity 90% phosphene threshold, PT) followed at random interstimulus intervals (ISIs; 15, 18, 21, 24, 27, 30, 35 and 40 msec) by a test stimulus (TS) over the left motor cortex to elicit a motor evoked potential (MEP) of ~1 mV from the right first dorsal interosseous muscle. RESULTS: In healthy subjects, a CS over V1 suppressed M1 at ISIs between 18 and 40 msec. Similar effects occurred in IGE patients without a PPR. This was not true in PPR-positive IGE patients, in whom this type of physiologic inhibition was significantly (p < 0.05) reduced. SIGNIFICANCE: IGE patients with a PPR have an overactive functional response of M1 to inputs traveling from V1. This may represent one core factor for the anterior spread of the PPR itself and for the origin of the abnormal epileptic motor phenomenon, such as myoclonus.
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Epilepsias Mioclónicas/diagnóstico , Epilepsias Mioclónicas/fisiopatología , Corteza Motora/fisiopatología , Estimulación Luminosa/métodos , Trastornos por Fotosensibilidad/diagnóstico , Trastornos por Fotosensibilidad/fisiopatología , Estimulación Magnética Transcraneal/métodos , Corteza Visual/fisiopatología , Adulto , Anciano , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/fisiopatología , Potenciales Evocados Motores/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiopatología , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: To investigate the predictors of seizure recurrence in women of childbearing age with idiopathic generalized epilepsy (IGE) who switched from valproate (VPA) to alternative antiseizure medications (ASMs) and compare the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) as VPA alternatives after switch. METHODS: This multicenter retrospective study included women of childbearing age diagnosed with IGE from 16 epilepsy centers. Study outcomes included worsening or recurrence of generalized tonic-clonic seizure (GTCS) at 12 months and 24 months after the switch from VPA to an alternative ASM. The comparative effectiveness of LEV and LTG as alternative ASM following VPA discontinuation was assessed through inverse probability treatment-weighted (IPTW) Cox regression analysis. RESULTS: We included 426 women with IGE, with a median (interquartile range) age at VPA switch of 24 (19-30) years and a median VPA dosage of 750 (500-1,000) mg/d. The most common reason for VPA switch was teratogenicity concern in 249 women (58.6%), and the most common ASM used in place of VPA was LEV in 197 (46.2%) cases, followed by LTG in 140 (32.9%). GTCS worsening/recurrence occurred in 105 (24.6%) and 139 (32.6%) women at 12 and 24 months, respectively. Catamenial worsening of seizures, higher VPA dosage during switch, multiple seizure types, and shorter duration of GTCS freedom before switch were independent predictors of GTCS recurrence or worsening at 12 months according to mixed multivariable logistic regression analysis. After internal-external validation through 16 independent cohorts, the model showed an area under the curve of 0.71 (95% CI 0.64-0.77). In the subgroup of 337 women who switched to LEV or LTG, IPTW Cox regression analysis showed that LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG (adjusted hazard ratio 0.59, 95% CI 0.40-0.87, p = 0.008) during the 24-month follow-up. DISCUSSION: Our findings can have practical implications for optimizing counselling and treatment choices in women of childbearing age with IGE and may help clinicians in making informed treatment decisions in this special population of patients. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for women with IGE switching from VPA, LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG.
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Epilepsia Generalizada , Ácido Valproico , Humanos , Femenino , Ácido Valproico/uso terapéutico , Estudios Retrospectivos , Anticonvulsivantes/uso terapéutico , Epilepsia Generalizada/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Levetiracetam/uso terapéutico , Lamotrigina/uso terapéutico , Inmunoglobulina E/uso terapéuticoRESUMEN
DNA deletions involving 6q22.1 region result in developmental encephalopathy (DE), often associated with movement disorders and epilepsy. The phenotype is attributed to the loss of the NUS1 gene included in the deleted region. Here we report three patients with 6q22.1 deletions of variable length all showing developmental delay, and rhythmic cortical myoclonus. Two patients had generalized seizures beginning in infancy. Myoclonic jerks had polygraphic features consistent with a cortical origin, also supported by cortico-muscular coherence analysis displaying a significant peak around 20 Hz contralateral to activated segment. Deletions in 6q22.1 region, similarly to NUS1 loss-of-function mutations, give rise to DE and cortical myoclonus via a haploinsufficiency mechanism. A phenotype of progressive myoclonic epilepsy (PME) may also occur.
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Epilepsias Mioclónicas , Epilepsia , Mioclonía , Humanos , Mioclonía/genética , Electroencefalografía , Epilepsia/genética , Convulsiones , Epilepsias Mioclónicas/genética , Receptores de Superficie CelularRESUMEN
Importance: After the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors' knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients. Objective: To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE. Design, Setting, and Participants: This was a multicenter, retrospective, comparative effectiveness cohort study analyzing data from patients followed up from 1994 to 2022. Patients were recruited from 22 primary, secondary, and tertiary adult and child epilepsy centers from 4 countries. Eligible patients were female individuals of childbearing age, diagnosed with IGE according to International League Against Epilepsy (2022) criteria and who initiated levetiracetam or lamotrigine as initial monotherapy. Patients were excluded due to insufficient follow-up after ASM prescription. Exposures: Levetiracetam or lamotrigine as initial monotherapy. Main Outcomes and Measures: Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy. Results: A total of 543 patients were included in the study, with a median (IQR) age at ASM prescription of 17 (15-21) years and a median (IQR) follow-up of 60 (24-108) months. Of the study population, 312 patients (57.5%) were prescribed levetiracetam, and 231 (42.5%) were prescribed lamotrigine. An IPTW-adjusted Cox model showed that levetiracetam was associated with a reduced risk of treatment failure after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR], 0.77; 95% CI, 0.59-0.99; P = .04). However, after stratification according to different IGE syndromes, the higher effectiveness of levetiracetam was confirmed only in patients with juvenile myoclonic epilepsy (JME; IPTW-adjusted HR, 0.47; 95% CI, 0.32-0.68; P < .001), whereas no significant differences were found in other syndromes. Patients treated with levetiracetam experienced adverse effects more frequently compared with those treated with lamotrigine (88 of 312 [28.2%] vs 42 of 231 [18.1%]), whereas the 2 ASMs had similar retention rates during follow-up (IPTW-adjusted HR, 0.91; 95% CI, 0.65-1.23; P = .60). Conclusions and Relevance: Results of this comparative effectiveness research study suggest the use of levetiracetam as initial alternative monotherapy in female patients with JME. Further studies are needed to identify the most effective ASM alternative in other IGE syndromes.
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Anticonvulsivantes , Epilepsia , Adulto , Niño , Humanos , Femenino , Masculino , Levetiracetam/uso terapéutico , Lamotrigina/uso terapéutico , Estudios Retrospectivos , Estudios de Cohortes , Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Inmunoglobulina E/uso terapéuticoRESUMEN
Paired associative stimulation (PAS) is a method commonly used in human studies of motor cortex synaptic plasticity. It involves repeated pairs of electrical stimuli to the median nerve and transcranial magnetic stimulation (TMS) of the motor cortex. If the interval between peripheral and TMS stimulation is around 2125 ms, corticospinal excitability is increased for the following 3060 min via a long term potentiation (LTP)-like effect within the primary motor cortex. Previous work has shown that PAS depends on the present and previous levels of activity in cortex, and that it can be modified by motor learning or attention. Here we show that simultaneous transcranial direct current stimulation (TDCS; 2 mA) over the cerebellum can abolish the PAS effect entirely. Surprisingly, the effect is seen when the PAS interval is 25 ms but not when it is 21.5 ms. There are two implications from this work. First, the cerebellum influences PAS effects in motor cortex; second, LTP-like effects of PAS have at least two different mechanisms. The results are relevant for interpretation of pathological changes that have been reported in response to PAS in people with movement disorders and to changes in healthy individuals following exercise or other interventions.
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Cerebelo/fisiología , Corteza Motora/fisiología , Plasticidad Neuronal/fisiología , Adulto , Estudios Cruzados , Estimulación Eléctrica , Potenciales Evocados Motores , Potenciales Evocados Somatosensoriales , Femenino , Humanos , Potenciación a Largo Plazo , Masculino , Persona de Mediana Edad , Estimulación Magnética Transcraneal , Adulto JovenRESUMEN
PURPOSE: To assess the visual system excitability of photosensitive patients with idiopathic generalized epilepsy (IGE) with the paired-pulse flash-evoked potential (paired F-VEP) technique. METHODS: We studied 19 photosensitive patients with IGE (16 women) showing a photoparoxysmal electroencephalographic (EEG) response (PPR). Twenty-two normal subjects of similar age and sex acted as controls (17 women). We recorded F-VEPs from occipital and central electrodes. Stimuli were single flashes, intermingled to flash pairs at the interstimulus interval (ISI) of 333, 125, 62.5, 50, 33, and 16.5 msec (i.e., at the internal frequency of 3, 8, 16, 20, 30, and 60 Hz). Recordings were done both with closed and open eyes. The single F-VEP was split into a "main complex" and a "late response," which were measured separately. As to paired stimuli, the "test" F-VEP emerged from electronic subtraction of the single F-VEP to the paired F-VEP. Grouped data were analyzed by means of nonparametric analyses of variance (ANOVAs). KEY FINDINGS: In patients, the single F-VEP showed some enhanced components in its early "main complex." Then, the "test" F-VEP behaved differently than controls, particularly if recorded with closed eyes, when the normal inhibition was abolished at given ISIs, corresponding to an internal frequency of 16-30 Hz. In patients with a posterior PPR, impaired inhibition was evident over the occipital region only, but in those with a widespread PPR, it also involved the central areas. SIGNIFICANCE: The paired F-VEP technique documents a defective inhibition in the visual system of photosensitive patients with IGE, whose features and timing likely underlie the PPR origin.
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Epilepsia Refleja/complicaciones , Potenciales Evocados Visuales/fisiología , Inhibición Psicológica , Discapacidades para el Aprendizaje/etiología , Adolescente , Adulto , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estimulación Luminosa , Factores de Tiempo , Grabación en Video , Adulto JovenRESUMEN
This study is aimed at investigating obsessive-compulsive disorder (OCD) in three groups of patients matched for age and gender; namely, focal dystonia (FD), hemifacial spasm (HFS), and healthy-control subjects (HC). All subjects were investigated with the Structured Clinical Interview for DSM-I, the Hospital Anxiety and Depression Scale, the Symptom Checklist-90, the Yale-Brown Obsessive-Compulsive Scale, and the Structured Clinical Interview for Obsessive-Compulsive Spectrum Self-Report, Lifetime Version (SCI-OBS-SR-LT). The prevalence of OCD was significantly higher in both FD and HFS than in HC participants. On the SCI-OBS, HFS patients showed higher scores than FD or HC for "contamination" and "aggressiveness." Despite the different pathophysiology, OCD is highly represented in both FD and HFS, with different thematic content characterizing the two conditions.
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Trastornos Distónicos/epidemiología , Espasmo Hemifacial/epidemiología , Trastorno Obsesivo Compulsivo/epidemiología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/complicaciones , Prevalencia , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Estadística como AsuntoRESUMEN
Objective.The pathophysiology of amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD) is still a matter of debate. Visual system might be precociously altered, especially for its cholinergic connections. We thus studied patients with aMCI compared to AD with paired-pulse flash-visual evoked potentials (paired-F-VEPs), a putative marker of cholinergic function. Methods. We enrolled 12 adult patients with aMCI and 12 with AD. 14 normal age- and sex-matched subjects acted as controls (HS). Stimuli were single flashes, with interspersed random flash pairs at critical interstimulus intervals (ISIs, 16.5 to 125â ms) with closed eyes. The "single" (unconditioned) F-VEP was split into a "main complex" (50 to 200â ms after the flash) and a "late response" (200 to 400â ms). As for paired stimulation, the "test" F-VEP emerged from electronic subtraction of the "single" F-VEP from the "paired"-F-VEP. Results. In the single F-VEP, P2 latency was prolonged in patients (aMCI and AD) compared to HS (p < .05). As to the paired F-VEPs, in aMCI the "late response" normal inhibition was abolished at ISIs 50-62.5â ms (p ≤ .016), compared to AD and controls. No changes were detected for the "main complex". Conclusions. Paired-F-VEPs demonstrate a defective neural inhibition in the visual system of patients with aMCI at critical intervals. It may represent a compensatory mechanism against neuronal loss, the failure of which may be involved in AD development. Paired-F-VEPs may warrant inclusion in future preclinical/clinical studies, to evaluate its potential role in the pathophysiology and management of aMCI.
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"Fixation-off sensitivity" (FOS) is an ideal human model for studying the features of epileptic discharges. Physiologically, FOS is expected to correspond to enhanced excitability of widespread cortical structures. To test this hypothesis, we measured by transcranial magnetic stimulation (TMS), the excitability level of the primary motor area in a 22-year-old woman with eyelid myoclonias and absences, who presented with generalized FOS. We also explored her visual system by pattern-reversal and flash-visual evoked potentials (VEPs). Both outside and within FOS, the cortical silent period was dramatically short, indicating defective γ-aminobutyric acid (GABA)(B) inhibition as a persistent background factor. The same was true for the short-interval intracortical inhibition, a TMS marker of cortical GABA(A) inhibition. The FOS state corresponded then to a pathologic enhancement of intracortical facilitation, a TMS marker of Glu/Asp transmission. During FOS, the flash VEP exhibited a hugely enhanced afterdischarge, expressing a pathologic overactivity of secondary visual areas. Within the limits of a single-case study, we thus provide electrophysiologic evidence supporting a grossly imbalanced cortical excitability, in both the frontal and posterior areas, as an important correlate of the present FOS subtype.
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Epilepsias Mioclónicas/fisiopatología , Fijación Ocular , Corteza Motora/fisiopatología , Estimulación Magnética Transcraneal , Estudios de Casos y Controles , Potenciales Evocados Motores , Potenciales Evocados Visuales , Femenino , Humanos , Adulto JovenRESUMEN
A 65-year-old woman presented with three "convulsive" events that were preceded by stabbing pain extending from the left submandible zone to the neck and ipsilateral ear. Video-electroencephalography captured a typical attack, where electrocardiography showed bradycardia for 17 seconds and asystole for at least 9 seconds. The patient lost consciousness while her head/gaze turned right. She then manifested tonic extension of her left limbs followed by adduction of her left limb and flexion of her right upper limb. Her gaze deviated upward and her left upper limb manifested swimming-like automatisms. The full episode lasted about 70 seconds, and the EEG showed progressive diffuse high-amplitude slowing. A diagnosis of convulsive syncope resulting from classic glossopharyngeal neuralgia was made. Carbamazepine led to steady remission. Glossopharyngeal neuralgia is a rare condition (incidence of 0.7/100.000/year), whereas the occurrence of syncope is about 20%, and that of convulsive syncope is about 5%.
Asunto(s)
Enfermedades del Nervio Glosofaríngeo/complicaciones , Síncope/complicaciones , Síncope/diagnóstico , Anciano , Animales , Anticonvulsivantes/uso terapéutico , Carbamazepina , Electrocardiografía , Electroencefalografía/métodos , Femenino , Enfermedades del Nervio Glosofaríngeo/tratamiento farmacológico , Humanos , Síncope/tratamiento farmacológico , Grabación de Cinta de Video/métodosRESUMEN
OBJECTIVE: To determine the feasibility of measuring scalp-recorded, flash-evoked, high-frequency EEG oscillations (F-HFOs) using a relatively simple technique. Furthermore, to assess whether F-HFOs are enhanced in photosensitive epileptic patients and if they might be proposed as a putative non-provocative biomarker of photosensitivity. METHODS: We studied 19 photosensitive patients with idiopathic generalized epilepsy, and 22 controls matched for demographic features. We extracted F-HFOs from the broadband scalp flash-visual evoked potential (b F-VEP) through appropriate filtering. We measured F-HFO amplitude, number and latency. Also, we carried out a time-frequency domain spectral F-HFO analysis. Inter-group statistics was performed. Within-groups, F-HFO features were correlated to the b F-VEP. RESULTS: The N3-N3I wave of the b F-VEP was significantly (p = 0.01) larger in patients compared to controls. The same was true for the inter-group F-HFO amplitude (p = 0.01). F-HFOs showed two main spectral peaks (â¼88 and â¼125 Hz), whose power was greater (p = 0.001) in patients than in controls. The â¼88 Hz peak power exceeded the upper normal range in 15/19 patients. Patients showed a significant (p = 0.04) correlation between the â¼88 Hz peak power and the size of the N3-N3I wave. SIGNIFICANCE: A simplified F-HFO measurement proved feasible. In patients, F-HFOs were enhanced in terms of both size and spectral power, suggesting a role in the generation of the photoparoxysmal response. Some spectral features of the F-HFOs may be proposed as a putative non-provocative marker of epileptic photosensitivity.
Asunto(s)
Epilepsia Generalizada , Epilepsia Refleja , Electroencefalografía , Epilepsia Refleja/diagnóstico , Potenciales Evocados Visuales , Humanos , Cuero CabelludoRESUMEN
PURPOSE: to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE). METHODS: a retrospective multicentric study involving 24 Italian neurology units was performed from March 2018 to June 2020. A shared case report form was used across participating centres to limit biases of retrospective data collection. Diagnosis and classification of SE followed the 2015 ILAE proposal. We considered a trial with BRV a success when it was the last administered drug prior the clinical and/or EEG resolution of seizures, and the SE did not recur during hospital observation. In addition, we considered cases with early response, defined as SE resolved within 6â¯h after BRV administration. RESULTS: 56 patients were included (mean age 62 years; 57 % male). A previous diagnosis of epilepsy was present in 21 (38 %). Regarding SE etiology classification 46 % were acute symptomatic, 18 % remote and 16 % progressive symptomatic. SE episodes with prominent motor features were the majority (80 %). BRV was administered as first drug after benzodiazepine failure in 21 % episodes, while it was used as the second or the third (or more) drug in the 38 % and 38 % of episodes respectively. The median loading dose was 100â¯mg (range 50-300â¯mg). BRV was effective in 32 cases (57 %). An early response was documented in 22 patients (39 % of the whole sample). The use of the BRV within 6â¯h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39-202; pâ¯=â¯0.002). No severe treatment emergent adverse events were observed. CONCLUSION: BRV proved to be useful and safe for the treatment of SE. Time to seizures resolution appears shorter when it is administered in the early phases of SE.
Asunto(s)
Estado Epiléptico , Anticonvulsivantes/uso terapéutico , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Pirrolidinonas/efectos adversos , Estudios Retrospectivos , Estado Epiléptico/tratamiento farmacológico , Resultado del TratamientoRESUMEN
OBJECTIVES: Altered cortical visuomotor integration has been involved in the pathophysiology of freezing of gait (FoG) in parkinsonism. The aim of this study was to assess the connections between the primary visual (V1) and motor (M1) areas with a paired-pulse, twin-coil transcranial magnetic stimulation (TMS) technique in patients with FoG. METHODS: Twelve Parkinson's disease (PD) patients suffering from levodopa-responsive-FoG (off-FoG) were compared with 12 PD patients without FoG and 12 healthy subjects of similar age/sex. In the "off" condition, visuomotor connections (VMCs) were assessed bilaterally. A conditioning stimulus over the V1 phosphene hotspot was followed at interstimulus intervals (ISIs) of 18 and 40ms by a test stimulus over M1, to elicit motor evoked potentials (MEPs) in the contralateral first dorsal interosseous muscle. RESULTS: Significant (P<0.01), bilateral effects due to VMCs were detected in all three groups, consisting of a MEP suppression at ISI 18 and 40ms. However, in PD patients with FoG, the MEP suppression was significantly (P<0.05) enhanced, both at ISI 18-40ms, in comparison with the other two groups. The phenomenon was limited to the right hemisphere. CONCLUSIONS: PD patients with FoG showed an excessive inhibitory response of the right M1 to inputs travelling from V1 at given ISIs. Right-sided alterations of the cortical visuomotor integration may contribute to the pathophysiology of FoG.