Timing of referral to evaluate for epilepsy surgery: Expert Consensus Recommendations from the Surgical Therapies Commission of the International League Against Epilepsy.

Epilepsy surgery is the treatment of choice for patients with drug-resistant seizures. A timely evaluation for surgical candidacy can be life-saving for patients who are identified as appropriate surgical candidates, and may also enhance the care of nonsurgical candidates through improvement in diagnosis, optimization of therapy, and treatment of comorbidities. Yet, referral for surgical evaluations is often delayed while palliative options are pursued, with significant adverse consequences due to increased morbidity and mortality associated with intractable epilepsy. The Surgical Therapies Commission of the International League Against Epilepsy (ILAE) sought to address these clinical gaps and clarify when to initiate a surgical evaluation. We conducted a Delphi consensus process with 61 epileptologists, epilepsy neurosurgeons, neurologists, neuropsychiatrists, and neuropsychologists with a median of 22 years in practice, from 28 countries in all six ILAE world regions. After three rounds of Delphi surveys, evaluating 51 unique scenarios, we reached the following Expert Consensus Recommendations: (1) Referral for a surgical evaluation should be offered to every patient with drug-resistant epilepsy (up to 70 years of age), as soon as drug resistance is ascertained, regardless of epilepsy duration, sex, socioeconomic status, seizure type, epilepsy type (including epileptic encephalopathies), localization, and comorbidities (including severe psychiatric comorbidity like psychogenic nonepileptic seizures [PNES] or substance abuse) if patients are cooperative with management; (2) A surgical referral should be considered for older patients with drug-resistant epilepsy who have no surgical contraindication, and for patients (adults and children) who are seizure-free on 1-2 antiseizure medications (ASMs) but have a brain lesion in noneloquent cortex; and (3) referral for surgery should not be offered to patients with active substance abuse who are noncooperative with management. We present the Delphi consensus results leading up to these Expert Consensus Recommendations and discuss the data supporting our conclusions. High level evidence will be required to permit creation of clinical practice guidelines.

Epilepsy Course and Developmental Trajectories in STXBP1-DEE.

Background and Objectives: Clinical manifestations in STXBP1 developmental and epileptic encephalopathy (DEE) vary in severity and outcome, and the genotypic spectrum is diverse. We aim to trace the neurodevelopmental trajectories in individuals with STXBP1-DEE and dissect the relationship between neurodevelopment and epilepsy. Methods: Retrospective standardized clinical data were collected through international collaboration. A composite neurodevelopmental score system compared the developmental trajectories in STXBP1-DEE. Results: Forty-eight patients with de novo STXBP1 variants and a history of epilepsy were included (age range at the time of the study: 10 months to 35 years, mean 8.5 years). At the time of inclusion, 65% of individuals (31/48) had active epilepsy, whereas 35% (17/48) were seizure free, and 76% of those (13/17) achieved remission within the first year of life. Twenty-two individuals (46%) showed signs of developmental impairment and/or neurologic abnormalities before epilepsy onset. Age at seizure onset correlated with severity of developmental outcome and the developmental milestones achieved, with a later seizure onset associated with better developmental outcome. In contrast, age at seizure remission and epilepsy duration did not affect neurodevelopmental outcomes. Overall, we did not observe a clear genotype-phenotype correlation, but monozygotic twins with de novo STXBP1 variant showed similar phenotype and parallel disease course. Discussion: The disease course in STXBP1-DEE presents with 2 main trajectories, with either early seizure remission or drug-resistant epilepsy, and a range of neurodevelopmental outcomes from mild to profound intellectual disability. Age at seizure onset is the only epilepsy-related feature associated with neurodevelopment outcome. These findings can inform future dedicated natural history studies and trial design.

Mutación de protocadherina 19 (PC-DH19), en paciente con epilepsia refractaria / Mutation of protocadherin 19 (PCDH19), in patients with refractory epilepsy

Paciente de 4 años de edad, con epilepsia de difícil manejo, cuya etiología se atribuye a patología autoinmune y que finalmente se diagnostica una mutación de protocadherina (PCDH19). Se discute la fisiopatología, características clínicas, exámenes y los posibles tratamientos.

Four-year-old patient with intractable epilepsy, whose etiology is attributed to autoimmune pathology and who is eventually diagnosed with a protocadherin mutation (PCDH19). Pathophysiology, clinical characteristics, examinations and possible treatments are discussed.

Phenomenology and clinical course of movement disorder in GNAO1 variants: Results from an analytical review.

GNAO1 variants were recently discovered as causes of epileptic encephalopathies and heterogeneous syndromes presenting with movement disorders (MDs), whose phenomenology and clinical course are yet undefined. We herein focused on GNAO1-related MD, providing an analytical review of existing data to outline the main MD phenomenology and management, clinical evolution and genotype-phenotype correlations. Reviewing 41 previously published patients and assessing 5 novel cases, a comprehensive cohort of 46 patients was analyzed, reassuming knowledge about genotypes, phenotypes, disease course and treatment of this condition. GNAO1-related MD consisted of a severe early-onset hyperkinetic syndrome, with prominent chorea, dystonia and orofacial dyskinesia. Symptoms are poorly responsive to medical therapy and fluctuate, with critical and life-threatening exacerbations, such as status dystonicus. The presence of a choreiform MD appears to be predictive of a higher risk of movement disorder emergency. Surgical treatments are sometimes effective, although severe disabilities persist. Differently from the early infantile epileptic encephalopathy phenotype (associated with loss of function variants), no clear correlation between genotype and MD phenotype emerged, although some variants recurred more frequently, mainly affecting exons 6 and 7.

Epilepsy for primary health care: a cost-effective Latin American E-learning initiative.

A lack of neurologists in Latin America forces primary health care providers to manage epilepsy. With the main goal of improving diagnostic and therapeutic management of patients with epilepsy through training of physicians in the primary health care level, the International League Against Epilepsy Education Commission (2013-2017) created a low-cost, regional, virtual course. The course, set-up in Moodle platform, was structured in eight modules, each lasting for a week. Teaching was based on written didactic material, videos, and interactive discussions, both in Spanish and Portuguese. Topics included epidemiology, diagnosis, classification, treatment, prognosis, social issues, and epilepsy policies. Each course was limited to 50 participants and priority was given to general practitioners. Certification was given to those approving the final examination. Since 2015, five courses have been developed, involving 143 participants from 17 countries and 21 tutors. Of the participants, 61% worked in primary health care services. A total of 129 participants (90%) completed the course, and 110 submitted the final examination with an approval rate of 95%. From 85 participants completing the course evaluation, 98% would recommend the course to other colleagues, and 99% showed interest in taking other similar courses. High self-confidence for the management of patients with epilepsy increased from 21% at baseline to 73% after the course. The online course on epilepsy for primary care physicians in Latin America was shown to be a cost-effective course, with good retention and excellent approval rates. Our current challenges include periodic updating, complete self-sustainability, and exploring different strategies to reach our target audience more effectively.

Hipermetabolismo temporal izquierdo en síndrome de Landau-Kleffner demostrado con PET F18-FDG: reporte de un caso con remisión metabólico-clínica postratamiento / Left temporal hypermetabolism detected in Landau-Kleffner syndrome with F18-FDG PET/CT: report of a case with metabolic and clinical remission after treatment

Brain F18-FDG Positron Emission Tomography (PET) has been used for studying focal epilepsy, with high sensitivity in detection of epileptogenic foci, even with normal magnetic resonance imaging (MRI). Some cases of Landau-Kleffner Syndrome (LKS) have shown PET abnormalities, mostly showing uni- or bilateral temporoparietal hypometabolism, although a heterogeneous group of alterations have been described. We report a case of LKS with a left hypermetabolic temporo-occipital area that responded to treatment, with clinical improvement and remission of PET hypermetabolic focus.

La positron emission tomography (PET) cerebral con F18-FDG ha sido utilizado para estudiar epilepsias focales con alta sensibilidad en la detección del área epileptógena, aun con resonancia magnética (RM) normal. La PET ha mostrado positividad en algunos casos de síndrome de Landau-Kleffner (SLK), la mayoría de las veces evidenciando hipometabolismo temporoparietal uni o bilateral, aunque un grupo heterogéneo de alteraciones asociadas ha sido descrito. Presentamos un caso de SLK con un área hipermetabólica temporooccipital izquierda, que respondió al tratamiento, con mejoría clínica y regresión del foco hipercaptante a la PET.

Consideraciones quirúrgicas propias de la epilepsia en niños, comentarios sobre Perú / Surgical considerations of epilepsy in children, comments about Peru

Las epilepsias resistentes a fármacos son aquellas donde hay persistencia de crisis pese a un tratamiento farmacológico óptimo. En niños su tratamiento es diferente al de los adultos, ya que las crisis producen daños encefálicos irrecuperables en un cerebro en desarrollo, por lo que se recomienda plantearla cirugía lo más precoz posible en casos de epilepsia refractaria y con alternativa terapéutica quirúrgica, incluso aunque las crisis lleven pocos meses de evolución. Entre el 25 al 33% de los niños presentan epilepsias resistentes a fármacos y la mitad de ellos son candidatos para iniciar un estudio prequirúrgico. En Perú aproximadamente 650 niños al año necesitarían cirugía, pero solo se operan unos pocos casos al año, si a esto agregamos los casos rezagados de los años anteriores, significa que hay miles de niños que esperan por una cirugía de la epilepsia. Este artículo revisa el estado del arte actual...

Drug resistant epilepsy is defined as the persistence of seizures, despite the optimal antiepileptic treatment. However the approach is different in children because they have a brain that is still developing. The International League Against Epilepsy proposed for these children to ôeliminate seizures as soon as possible to optimize cognitive development, and improve behavior and quality of lifeõ. About 25 to 33% of epileptic children have refractory epilepsy and half of them require a pre-surgical evaluation. Around 650 children in Peru need epilepsy surgery treatment every year, but few patients get access to it. If we include cases of previous years, the waiting list in Peru is over 1,000 children. This paper analyzed the state of art in epilepsy surgery in children...

Normalización de trastornos de sueño y su efecto en pacientes con epilepsia refractaria / Effects of sleep disorders normalization in patients during the use of antiepileptic drugs

Los trastornos del sueño son un problema frecuente y subdiagnosticado en niños con cuadros neurológicos y en particular con epilepsias refractarias. Evaluamos los efectos de normalización rápida de los patrones de sueño sobre la refractariedad de la epilepsia. Pacientes y Método: Se ingresaron al estudio todos los pacientes pediátricos con alteración severa del ciclo sueño-vigilia y epilepsia refractaria en control en el Servicio de Neuropsiquiatría Infantil del Hospital Clínico San Borja-Arriarán y Liga contra la Epilepsia, Santiago, Chile, entre Marzo 2004 y Marzo 2008. Cada paciente fue su propio control. Durante el primer mes se solicitó a los padres completar un registro diario de frecuencia y tipo de crisis epiléptica y del ciclo sueño-vigilia de su hijo (a). A contar del segundo mes se implementó un tratamiento para normalizar el ciclo sueño-vigilia utilizando luminoterapia, hábitos estrictos de sueño y melatonina, 30 min antes de la hora de dormir. La terapia antiepiléptica no se modificó durante los primeros seis meses de tratamiento. Resultados: Los once pacientes ingresados normalizaron el ciclo sueño-vigilia durante el primer mes de tratamiento. Diez de 11 casos mostraron una reducción dramática de la frecuencia de crisis por día, mayor a un 85 por ciento, durante los primeros tres meses de intervención, independientemente del tipo de crisis, que se mantuvo por más de un año de seguimiento (13-43 meses). En cinco pacientes se discontinuó la melatonina después de un año de tratamiento, sin que hubiese deterioro del patrón de sueño o aumento en la frecuencia de crisis. Conclusión: Es frecuente el subdiagnóstico de trastorno de sueño en niños con epilepsias refractarias. La normalización del patrón de ciclo sueño-vigilia puede disminuir dramáticamente la frecuencia de crisis y por lo tanto mejorar la calidad de vida de los pacientes y sus familias...

Sleep disorders are a frequent and underdiagnosed problem in children with neurological problems, specially in children with refractory epilepsies. We evaluated the effects of fast normalization of sleep pattern on epilepsy refractoriness. Patients and methods: We enrolled all pediatric patients from March 2004 to March 2008, with severe alterations of the sleep-wake pattern and refractory epilepsy, attending to the Neuropsychiatry Service, Hospital Clínico San Borja-Arriarán and League against Epilepsy from Santiago, Chile. Each patient was his own control. Parents were asked to complete a diary during the first month after enrollment with frequency, type of seizures and sleep-wake cycle of each patient. After the month, sleep-wake cycle was normalized using morning luminotherapy, strict sleep habits and melatonin, 30 minutes before bedtime. Antiepileptic therapy was not modified during the first six months. Results: All patients normalized the sleep-wake cycle during the first month treatment. Ten of 11 patients showed a dramatic reduction of seizure frequency (over 85 percent of total day seizures) during the first three months of intervention, independently from the seizure type that has maintained for more than a year (13–43 months) follow-up. Melatonin was discontinued in five patients after a year of treatment, with no deterioration of sleep pattern or seizures frequency. Conclusions: Sleep disorders in children with refractory epilepsies are frequently underestimated. The normalization of the sleep-wake pattern can diminish seizures dramatically, improving patients and family quality of life. This point must be always taken into account before considering a patient refractory to antiepileptic drugs and adding new drugs to polytherapy.

Effect of music on the recovery of a patient with refractory nonconvulsive status epilepticus.

The effect of music in epilepsy has been reported as beneficial but mainly in the interictal condition. There are no reports of the effect of music in an acute condition such as status epilepticus. Herein, we report a remarkable response to music in a patient with medically refractory nonconvulsive status epilepticus.

Incidencia de variantes normales de aspecto epileptiforme en electroencefalogramas normales: estudio prospectivo y revisión de la literatura / Incidence of normal variants patterns that mimic epileptiform discharges in routine normal EEGs: prospective study and literature review

El reconocimiento de variantes normales en electroencefalogramas de rutina es de gran importancia para reducir errores diagnósticos, especialmente en epilepsia ya que la mayoría de estas variantes presenta morfología aguda o epileptiforme y suelen ser foccales. No existen en nuestro medio trabajos que reporten esta actividad y en la práctica clínica sólo una de ellas es descrita ocasionalmente, lo que motiva esta investigación. Objetivo. Conocer la incidencia de variantes normales en electroencefalogramas normales en mayores de un año, tomados de una población de laboratorio de EEG. Material y Métodos. Se estudia prospectivamente la presencia de variantes normales (espigas "wicket", espigas positivas a 14 y 6 Hz, variante psicomotora, pequeñas espigas de sueño, ondas lentas de la senectud, pseudo petit mal, theta del despertar, alfa dicroto, ritmo µ, espigas fantasmas y descargas rítmicas subclínicas del adulto), en todos los EEG de rutina (estándares o post privación de sueño), practicados a mayores de un año en el Laboratorio de Electroencefalografía del Hospital Clínico de la Universidad Católica de Chile entre Octubre de 1999 y Septiembre de 2000. Todos los registros fueron analizados por alguno de los autores. Resultados. De un total de 1816 registros normales, el 4,8 por ciento (n=88) mostró alguna variante normal, llegando en el grupo sobre los 60 años a 11,4 por ciento. Del total de variantes las más frecuentemente encontradas fueron el ritmo µ (45,5 por ciento), las espigas wicket (21,6 por ciento) y las variantes psicomotoras (9,1 por ciento). No se pesquisaron espigas fantasmas ni descargas rítmicas subclínicas del adulto. Conclusión. Las variantes normales de aspecto epileptiforme se encuentran con relativa frecuencia en EEGs normales de rutina en nuestro medio, especialmente en personas sobre 60 años de edad y conviene tenerlas presente para evitar sobrediagnóstico de actividad genuinamente patológica.