Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program.

OBJECTIVE: This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP). METHOD: This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, and ≥50%) or worsening in seizure frequency at 3-, 6-, and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; ≥90%, ≥75%, and ≥50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness. SIGNIFICANCE: In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation.

Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy.

AIM: To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP). METHODS: This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together. CONCLUSIONS: Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP.

COVID-19 prevalence and mortality in people with epilepsy: A nation-wide multicenter study.

BACKGROUND: To assess the prevalence, severity, and mortality of COVID-19 in people with epilepsy (PWE) and evaluate seizure control in PWE during and after COVID-19. METHODS: Retrospective, observational, multicenter study conducted in 14 hospitals. Medical records of randomly selected PWE followed at neurology outpatient clinics were reviewed. Proportion of PWE with a positive test for SARS-CoV-2 during 2020 was calculated. Risk factors associated with COVID-19 and its morbimortality were evaluated. RESULTS: 2751 PWE were included, mean age 48.8 years (18-99), 72.4% had focal epilepsy, and 35% were drug-refractory. COVID-19 prevalence in PWE was 5.53%, while in the Spanish population was 4.26%. Proportion of admissions to hospital, ICU, and deaths in PWE were 17.1%, 2%, and 4.61% of COVID-19 cases, while in Spanish population were 10.81%, 0.95%, and 2.57%, respectively. A severe form of COVID-19 occurred in 11.8%; dyslipidemia, institutionalization at long-term care facilities, intellectual disability, and older age were associated risk factors. Older age, hypertension, dyslipidemia, cardiac disease, and institutionalization were associated with mortality from COVID-19. Seizure control was stable in 90.1% of PWE during acute COVID-19, while 8.6% reported an increase in seizure frequency. During post-COVID-19 follow-up, 4.6% reported seizure control worsening. CONCLUSIONS: COVID-19 was moderately prevalent in PWE. One out of 5 patients required medical attention and 4.6% died due to COVID-19. Older age, dyslipidemia, institutionalization, and intellectual disability were significant risk factors associated with severe COVID-19. Seizure control remained stable during COVID-19 and throughout long-term follow-up in most PWE who contracted the infection.

Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: Experience from a national multicenter registry.

OBJECTIVE: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). METHODS: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. RESULTS: A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1-57) with a median dose of 4 mg (range = 2-10). The retention rates at 3, 6, and 12 months and last follow-up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log-rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3-26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure-free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow-up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1-8.33, P = .046). SIGNIFICANCE: PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.

Epilepsy surgery beyond 50 years: Long-term seizure and cognitive outcomes.

INTRODUCTION: Surgery is a well-demonstrated effective treatment for patients with refractory epilepsy. However, there are scarce data about the efficacy in older patients. Endpoint was to evaluate the outcome of epilepsy surgery in pharmacorresistant patients operated in middle-late adulthood. METHODS: We conducted a retrospective observational study including patients who underwent a epilepsy surgery at age ≥ 50. Presurgical clinical data, type of surgery, and postsurgical seizure outcome and neurological complications, including neuropsychological assessment were analyzed. Minimum post-surgical follow-up was 1 year. RESULTS: We identified 38 patients (22 males, 17 females) out of 350 patients who underwent a resective surgery with curative intention in our Epilepsy Unit (12%). Median age at surgery was 56 years (50-69), with median epilepsy duration of 42 years (4-67). Neuroimaging showed focal epileptogenic lesions in 37 patients, mainly mesial temporal sclerosis (21). Presurgical neuropsychological evaluation was available in 38 patients: 35 had deficits, mostly in verbal or visual memory. Twenty-eight patients underwent standard temporal lobectomy with amygdalohippocampectomy, 7 lesionectomy and 4 lobectomy. Median follow-up was 4.46 years (1-9.75). A good outcome was achieved by 86.8% (28 Engel I; 5 Engel II); 5 patients were studied with SEEG, without any complications. None had postsurgical permanent neurological complications. From 22 patients with available post-surgical neuropsychological assessment, 16 scored lower than in pre-surgical one, mainly in memory domain. CONCLUSION: Surgical treatment of long-term refractory epilepsy in patients ≥50 years can be effective and safe. Post-surgical memory decline is a frequent side effect, but with a low impact in daily life.

Desafíos diagnósticos en epilepsia / Diagnostic challenges in epilepsy

Introducción. Las crisis epilépticas y la epilepsia son parte de la práctica clínica diaria en neurología. No obstante, el número de diagnósticos falsos positivos es sorprendentemente alto. Casi uno de cada cinco pacientes tratado por epilepsia en realidad no tiene ese diagnóstico, un porcentaje elevado teniendo en cuenta las consecuencias sociomédicas que conlleva el diagnóstico de epilepsia. Objetivos. Resumir los desafíos diagnósticos más importantes en epilepsia, describir posibles fuentes de error en el diagnóstico y proporcionar consejos sobre cómo evitarlos. Desarrollo. La epilepsia se caracteriza por una tendencia a sufrir crisis epilépticas no provocadas. El mayor obstáculo al diagnosticar una epilepsia radica en que las crisis epilépticas son fenómenos transitorios que ocurren relativamente con poca frecuencia y el médico que realiza el diagnóstico raramente llega a verlas. Además, existen otros eventos clínicos, como por ejemplo síncopes o crisis no epilépticas, que pueden tener una apariencia similar a las crisis epilépticas y, en consecuencia, confundirse con ellas. Finalmente, al interpretar las dos técnicas diagnósticas complementarias más importantes en epileptología, el electroencefalograma y la resonancia magnética cerebral, deben tenerse en cuenta los errores más comunes para prevenir diagnósticos erróneos. Conclusiones. El diagnóstico de una epilepsia es un reto y debe basarse en una historia clínica detallada y específica. Si desde el inicio existen dudas razonables sobre el diagnóstico de epilepsia o si el paciente no responde bien al tratamiento antiepiléptico, recomendamos derivar al paciente a un centro especializado que establezca un diagnóstico definitivo

Introduction. Epileptic seizures and epilepsy are part of daily clinical practice in neurology. Yet, the number of false positive diagnoses is surprisingly high. Almost one out of every five patients treated for epilepsy does not really have this diagnosis, which is a high percentage bearing in mind the social and medical consequences that being diagnosed with epilepsy entails. Aims. To summarise the most important diagnostic challenges in epilepsy, to describe possible sources of diagnostic error and to offer advice on how to avoid them. Development. Epilepsy is characterised by a tendency to suffer unprovoked epileptic seizures. The greatest obstacle when it comes to diagnosing a case of epilepsy is the fact that epileptic seizures are transient phenomena that occur relatively infrequently and the physician who must carry out the diagnosis will rarely see them. Moreover, there are other clinical events, such as syncopes or non-epileptic seizures, that may be similar to epileptic seizures in appearance and, consequently, can be mistaken for them. Finally, when interpreting the two most important complementary diagnostic techniques in epileptology, the electroencephalogram and magnetic resonance imaging of the brain, the most common errors must be taken into account in order to prevent mistaken diagnoses. Conclusions. The diagnosis of epilepsy is a challenge and must be based on a detailed and specific medical record. If there are any reasonable doubts, from the outset, about the diagnosis of epilepsy or if the patient does not respond well to the antiepileptic treatment, we recommend referring the patient to a specialised centre to establish a definitive diagnosis

Antiepileptic drug reduction and increased risk of stimulation-evoked focal to bilateral tonic-clonic seizure during cortical stimulation in patients with focal epilepsy.

INTRODUCTION: Stimulation-evoked focal to bilateral tonic-clonic seizure (FBTCS) can be a stressful and possibly harmful adverse event for patients during cortical stimulation (CS). We evaluated if drug load reduction of antiepileptic drugs (AEDs) during CS increases the risk of stimulation-evoked FBTCS. MATERIAL AND METHODS: In this retrospective cohort study, we searched our local database for patients with drug-resistant epilepsy who underwent invasive video-EEG monitoring and CS in the University Hospital la Fe Valencia from January 2006 to November 2016. The AED drug load was calculated with the defined daily dose. We applied a uni- and multivariate logistic regression model to estimate the risk of stimulation-evoked FBTCS and evaluate possible influencing factors. Furthermore, we compared patients whose AEDs were completely withdrawn with those whose AEDs were not. RESULTS: Fifty-eight patients met the inclusion criteria and were included in the analysis. Stimulating 3806 electrode contact pairs, 152 seizures were evoked in 28 patients (48.3%). Ten seizures (6.6%) in seven patients (12.1%) evolved to FBTCS. In the univariate and multivariate analysis, a 10% reduction in drug load was associated with an increase of the odds ratio (OR) of stimulation-evoked FBTCS by 1.9 (95%-CI 1.2, 4.0, p-value=0.04) and 1.9 (95%-CI 1.2, 4.6, p-value=0.04), respectively. In patients, whose AEDs were completely withdrawn the OR of FBTCS increased by 9.1 (95%CI 1.7, 69.9, p-value=0.01) compared with patients whose AEDs were not completely withdrawn. No other factor (implantation type, maximum stimulus intensity, number of stimulated contacts, history of FBTCS, age, gender, or epilepsy type) appears to have a significant effect on the risk of stimulation-evoked FBTCS. CONCLUSIONS: The overall risk of stimulation-evoked FBTCS during CS is relatively low. However, a stronger reduction and, especially, a complete withdrawal of AEDs are associated with an increased risk of stimulation-evoked FBTCS.

Age at surgery as a predictor of cognitive improvements in patients with drug-resistant temporal epilepsy.

Temporal lobe epilepsy (TLE) surgery is an effective procedure that can produce cognitive changes. However, the prognostic factors related with cognitive outcomes need to be better understood. The aim of the present study is to know if age at surgery is a reliable predictor of verbal memory competence and considering factors such as: hemisphere; type of surgery; pre-surgical seizure frequency; and epilepsy duration. Sixty-one typically dominant patients with drug-resistant TLE (34 with left TLE [L-TLE] and 27 with right TLE [R-TLE]) underwent a neuropsychological assessment before and a year after surgery. Results showed that R-TLE patients had better evolution in short- and long-term verbal memory and naming than L-TLE patients (for all, p >.04). L-TLE patients also more frequently showed a strong and reliable decline in these functions than R-TLE patients. No effects for gender or type of surgery were found. From a multivariate approach, patients with improvements in verbal competence underwent surgery at earlier ages and suffered epilepsy for less time (for all, p <0.4). The relevance of age at surgery was confirmed as a predictor of long-term verbal memory changes, although the frequency of partial seizures also explains, at least partially, these changes. In addition, the frequency of partial seizures explains short-term verbal memory changes. These results emphasize the importance of early intervention, independently of the resected hemisphere, in order to minimize the cognitive side-effects of epilepsy treatment, as well the need to consider cognitive functions as related processes and network dependent.

Psychiatric symptoms after temporal epilepsy surgery. A one-year follow-up study.

Psychiatric symptoms must be considered in patients with refractory temporal lobe epilepsy after epilepsy surgery. The main objectives of our study were to describe clinical and socio-demographical characteristics of a cohort of patients with pharmacoresistant temporal lobe epilepsy who underwent temporal lobe epilepsy surgery, and moreover, to evaluate possible risk factors for developing psychiatric symptoms. In order to achieve those goals, we conducted a prospective evaluation of psychopathology throughout the first year after surgery in a clinical sample of 72 patients, by means of three clinical rated measures; the Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), and the Brief Psychiatric Rating Scale (BPRS). The psychopathological evaluations were performed by an experienced psychiatrist. A presurgical evaluation was done by a multidisciplinary team (that includes neurologist, psychiatrist, neurosurgeon, neurophysiologist, radiologists, and nuclear medicine specialist) in all patients. The decision to proceed to surgery was taken after a surgical meeting of all members of the Multidisciplinary Epilepsy Unit team. The psychiatrist conducted two postoperative assessments at 6months and 12months after surgery. The main finding was that past history of mental illness (patients who were receiving psychiatric treatment prior to the baseline evaluation) was a risk factor for anxiety, depression, and psychosis after temporal lobe epilepsy surgery.

Epilepsy surgery in drug resistant temporal lobe epilepsy associated with neuronal antibodies.

We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel's classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients.

NEOPLASM study: Real-life use of lacosamide in patients with brain tumor-related epilepsy.

BACKGROUND: The choice of antiepileptic drug (AED) therapy in patients with brain tumor-related epilepsy (BTRE) is complicated, and there are a lack of robust clinical trial data to date. METHODS: The NEOPLASM (Neuroncologic Patients treated with LAcoSaMide) study was a 6-month, multicenter, retrospective, observational study in patients with BTRE treated with lacosamide. Patients were started on lacosamide because of a lack of efficacy or adverse events (AEs) with prior AEDs or suitability versus other AEDs, according to clinical practice. The primary efficacy variable was the seizure-free rate at 6months. Safety variables included the proportion of patients with an AE and the proportion with an AE that led to discontinuation. RESULTS: Overall, 105 patients from 14 hospital centers were included in the analysis. Treatment with lacosamide for 6months resulted in a 30.8% seizure-free rate, and 66.3% of patients had a ≥50% seizure reduction (responders). In the subset of patients included because of a lack of efficacy with prior AEDs, seizure-free rates were 28.0%, and 66.7% of patients were responders. No statistically significant differences in efficacy were observed according to the mechanism of action or enzyme-inducing properties of concomitant AEDs. Adverse events were reported by 41.9% of patients at 6months, and 4.7% of them led to discontinuation. The most common AEs were somnolence/fatigue and dizziness. Notably, 57.1% of the patients who were switched to lacosamide because of AEs with their previous therapy did not report any AE at 6-month follow-up. CONCLUSIONS: In this open-label, observational study, lacosamide appeared to be effective and well tolerated in a large population of patients with BTRE. Lacosamide may therefore be a promising option for the treatment of patients with BTRE.

Hiperfamiliaridad para las caras en la epilepsia del lóbulo temporal / Hyperfamiliarity for faces in temporal lobe epilepsy

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Aberrant mitochondria in a Bethlem myopathy patient with a homozygous amino acid substitution that destabilizes the collagen VI α2(VI) chain.

Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD) sit at opposite ends of a clinical spectrum caused by mutations in the extracellular matrix protein collagen VI. Bethlem myopathy is relatively mild, and patients remain ambulant in adulthood while many UCMD patients lose ambulation by their teenage years and require respiratory interventions. Dominant and recessive mutations are found across the entire clinical spectrum; however, recessive Bethlem myopathy is rare, and our understanding of the molecular pathology is limited. We studied a patient with Bethlem myopathy. Electron microscopy of his muscle biopsy revealed abnormal mitochondria. We identified a homozygous COL6A2 p.D871N amino acid substitution in the C-terminal C2 A-domain. Mutant α2(VI) chains are unable to associate with α1(VI) and α3(VI) and are degraded by the proteasomal pathway. Some collagen VI is assembled, albeit more slowly than normal, and is secreted. These molecules contain the minor α2(VI) C2a splice form that has an alternative C terminus that does include the mutation. Collagen VI tetramers containing the α2(VI) C2a chain do not assemble efficiently into microfibrils and there is a severe collagen VI deficiency in the extracellular matrix. We expressed wild-type and mutant α2(VI) C2 domains in mammalian cells and showed that while wild-type C2 domains are efficiently secreted, the mutant p.D871N domain is retained in the cell. These studies shed new light on the protein domains important for intracellular and extracellular collagen VI assembly and emphasize the importance of molecular investigations for families with collagen VI disorders to ensure accurate diagnosis and genetic counseling.

Recognition of facial emotions and identity in patients with mesial temporal lobe and idiopathic generalized epilepsy: an eye-tracking study.

PURPOSE: To describe visual scanning pattern for facial identity recognition (FIR) and emotion recognition (FER) in patients with idiopathic generalized (IGE) and mesial temporal lobe epilepsy (MTLE). Secondary endpoint was to correlate the results with cognitive function. METHODS: Benton Facial Recognition Test (BFRT) and Ekman&Friesen series were performed for FIR and FER respectively in 23 controls, 20 IGE and 19 MTLE patients. Eye movements were recorded by a Hi-Speed eye-tracker system. Neuropsychological tools explored cognitive function. RESULTS: Correct FIR rate was 78% in controls, 70.7% in IGE and 67.4% (p=0.009) in MTLE patients. FER hits reached 82.7% in controls, 74.3% in IGE (p=0.006) and 73.4% in MTLE (p=0.002) groups. IGE patients failed in disgust (p=0.005) and MTLE ones in fear (p=0.009) and disgust (p=0.03). FER correlated with neuropsychological scores, particularly verbal fluency (r=0.542, p<0.001). Eye-tracking revealed that controls scanned faces more diffusely than IGE and MTLE patients for FIR, who tended to top facial areas. A longer scanning of the top facial area was found in the three groups for FER. Gap between top and bottom facial region fixation time decreased in MTLE patients, with more but shorter fixations in bottom facial region. However, none of these findings were statistically significant. CONCLUSION: FIR was impaired in MTLE patients, and FER in both IGE and MTLE, particularly for fear and disgust. Although not statistically significant, those with impaired FER tended to perform more diffuse eye-tracking over the faces and have cognitive dysfunction.

Clinical phenotypes within non-surgical patients with mesial temporal lobe epilepsy caused by hippocampal sclerosis based on response to antiepileptic drugs.

PURPOSE: To evaluate evolution and elucidate clinical phenotypes related to prognosis of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) treated exclusively with antiepileptic drugs (AED). METHODS: Forty-seven out of 68 MTLE-HS patients treated between January 2005 and June 2010 were retrospectively studied for demographic, clinical and outcome data. The population was divided into drug-responder and drug-resistant patients; the latter was divided, according to the duration of the seizure-free periods along their evolution, into patients with at least one seizure-free period longer than one year and those with shorter periods. Variables were compared between drug-responders vs drug-resistants and drug-resistants with long seizure-free periods vs drug-resistants without it. RESULTS: There were 7 (15%) drug-responders, 39 (83%) drug-resistants and 1 patient (2%) with an undetermined response. Eighteen (46%) drug-resistant individuals had seizure-free periods longer than one year, with mean duration of 46 months (3.8 years). Since no factor was statistically associated with long seizure-free period within drug-resistants, we can clinically distinguish two phenotypes: women with left HS and late onset of seizures, with poor prognosis, and men with right HS and earlier appearance of seizures, attaining a better outcome. Twenty out of 47 (42.5%) patients followed an intermittent pattern of epilepsy. CONCLUSIONS: Non-surgical MTLE-HS drug-resistant patients can achieve long seizure-free periods with AED, but relapses are common. Female gender, left or bilateral lesion and later onset of seizures seem to be bad prognosis factors within MTLE-HS drug-resistant patients.

[Non-convulsive status epilepticus in the 21st century: clinical characteristics, diagnosis, treatment and prognosis]. / Estado epiléptico no convulsivo en el siglo xxi: clínica, diagnóstico, tratamiento y pronóstico.

Non-convulsive status epilepticus is a significant issue for a neurologist because, despite its low prevalence, it mimics other pathologies, with therapeutics and prognostic outcomes. Diagnosis is based on clinical features, mainly mental status or impaired consciousness and electroencephalographic changes, so electroencephalogram is the first exploration we must perform with clinical suspicion. There are three clinical forms: generalized or absence status, with diffuse epileptiform discharges; focal, with epileptic discharges located in a specific brain area and may not affect consciousness; and subtle, with diffuse or local epileptic activity after a tonic-clonic seizure or convulsive status and limited or no motor activity. Treatment are benzodiazepines and antiepileptic drugs; anesthetic drugs are only recommended for patients with subtle status and in some with partial complex status. Prognosis is mainly determined by etiology and associated brain damage.

Estado epiléptico no convulsivo en el siglo xxi: clínica, diagnóstico, tratamiento y pronóstico / Non-convulsive status epilepticus in the 21st century: clinical characteristics, diagnosis, treatment and prognosis

Resumen. El estado epiléptico no convulsivo es una patología importante para el neurólogo porque, a pesar de su baja prevalencia, puede confundirse con otras entidades, con las consiguientes implicaciones terapéuticas y pronósticas. El diagnóstico está basado en cambios clínicos, fundamentalmente del estado mental o nivel de conciencia habitual del paciente, y electroencefalográficos, por lo que el electroencefalograma es la herramienta básica que hemos de utilizar ante la sospecha clínica. Existen tres tipos: generalizado o estado de ausencia, con grafoelementos epileptiformes difusos en el trazado electroencefalográfico; focal, con descargas localizadas en una área cerebral concreta y que pueden no afectar a la conciencia; y sutil, con actividad epileptiforme focal o difusa asociada a poca o ninguna actividad motora tras una crisis tonicoclónica generalizada o un estado convulsivo. El tratamiento consta de benzodiacepinas y fármacos antiepilépticos; los anestésicos están indicados únicamente en el estado sutil y casos graves de estado parcial complejo. El pronóstico depende principalmente de la etiología y el daño cerebral asociado (AU)

Summary. Non-convulsive status epilepticus is a significant issue for a neurologist because, despite its low prevalence, it mimics other pathologies, with therapeutics and prognostic outcomes. Diagnosis is based on clinical features, mainly mental status or impaired consciousness and electroencephalographic changes, so electroencephalogram is the first exploration we must perform with clinical suspicion. There are three clinical forms: generalized or absence status, with diffuse epileptiform discharges; focal, with epileptic discharges located in a specific brain area and may not affect consciousness; and subtle, with diffuse or local epileptic activity after a tonic-clonic seizure or convulsive status and limited or no motor activity. Treatment are benzodiazepines and antiepileptic drugs; anesthetic drugs are only recommended for patients with subtle status and in some with partial complex status. Prognosis is mainly determined by etiology and associated brain damage (AU)