Effectiveness of vagal nerve stimulation in medication-resistant epilepsy. Comparison between patients with and without medication changes.

BACKGROUND: Vagal nerve stimulation (VNS) response is not immediate. A progressive decline in seizure frequency is usually found during a period of 12-18 months after implantation. During this time, the patient's medication is usually modified, which can create doubts about whether their clinical improvement is due to medication changes or to VNS itself. Our goal is to compare two groups of patients treated with VNS, with and without changes in their medication. METHODS: We prospectively analyze 85 patients who were treated with VNS in our hospital between 2005 and 2014. In 43 patients, changes in the antiepileptic drugs (EAD) were not allowed during the postoperative follow-up and they were compared with 42 patients who were left at the option of neurologist make changes in medication. We analyzed the clinical situation at 18 months and compared the two groups. RESULTS: Overall, 54.1% of patients had a reduction in seizures of 50% or higher (responders). In the group with no changes in medication, responders reached 63%, while in the group in which changes in medication were allowed, 45.2% were responders. Between responders and non-responders, there were no statistical differences in type of epilepsy, frequency, previous surgery, or intensity of stimulation. CONCLUSIONS: We did not find a statistical difference in seizure frequency reduction between patients with or without changes in medication during their follow-up, so changes in medication did not improve the outcome. Furthermore, the absence of changes in AED can help to optimize the parameters of the stimulator in order to improve its effectiveness.

Clasificación de las lesiones estructurales en resonancia magnética. Implicaciones quirúrgicas en pacientes con epilepsia farmacorresistente. Réplica / Classification of structural lesions in magnetic resonance imaging. Surgical implications in drug-resistant epilepsy patients. Reply

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Clasificación de las lesiones estructurales en resonancia magnética. Implicaciones quirúrgicas en pacientes con epilepsia farmacorresistente / Classification of structural lesions in magnetic resonance imaging. Surgical implications in drug-resistant epilepsy patients

Introducción. En la selección quirúrgica del paciente con epilepsia farmacorresistente, el papel de la resonancia magnética (RM) no se ha cuantificado hasta el momento. Presentamos la experiencia en nuestra Unidad de Cirugía de la Epilepsia. Pacientes y métodos. Se estudiaron retrospectivamente los pacientes intervenidos por epilepsia farmacorresistente. Distinguimos dos períodos: 1990-2000 (RM de 0,5 T) y 2001-2008 (RM de 1,5 T). La RM preoperatoria se clasificó en tres grupos: RM con lesión quirúrgica (LQ), RM orientativa (LO) y RM normal (NL). También se efectuó una clasificación anatomopatológica similar. Se correlacionaron las distintas clasificaciones y los resultados quirúrgicos. Resultados. Período 1990-2000: 151 pacientes. El 70% quedó en las clases de Engel I o II. Según la RM, los resultados fueron: LQ, 87%; LO, 65%; y NL, 57%. Las diferencias fueron estadísticamente significativas. Período 2001-2008: 114 pacientes. El 89% quedó en las clases de Engel I o II. Según la RM: LQ, 100%; LO, 90%; y NL, 81%. Las diferencias fueron estadísticamente significativas. Los pacientes con epilepsia del lóbulo temporal y extratemporal con LQ tuvieron un 100% de control; con LO, el 95% con epilepsia del lóbulo temporal y el 43% con estado epiléptico; en aquellos pacientes sin lesión (NL), el 88% con epilepsia del lóbulo temporal se controló frente al 50% con estado epiléptico. Conclusiones. La RM es una herramienta eficaz en la selección de candidatos quirúrgicos en la epilepsia. La LQ asocia muy buen pronóstico. En la epilepsia del lóbulo temporal se pueden obtener muy buenos resultados (80-90% de control) a pesar de una RM normal. En el estado epiléptico, las LO pueden tener peor resultado que la NL en la RM (AU)

Introduction. The presence of a structural lesion in the preoperative magnetic resonance imaging (MRI) of drug-resistant epilepsy patients has been usually associated with a favourable surgical outcome. We present our experience in our Epilepsy Surgery Unit. Patients and methods. Clinical records from 265 patients, operated on from 1990-2010 in our institution, were reviewed. Patients were classified, according to MRI findings, into three groups: surgical lesion (SL), tumors or vascular malformations requiring surgery ‘per se’; orientative lesion (OL), dysplasia, atrophy or mesial temporal sclerosis; and (NL) group, with normal MRI. Seizure outcomes were analysed in relation to this classification. Results. Period 1990-2000, 151 patients: 87% of SL, 65% of OL and 57% of NL patients were in Engel class I or II at the two-year follow-up. Among temporal lobe epilepsy cases (TLE), 87% of SL, 67% of OL and 56% of NL patients achieved seizure control. Differences were statistically significative. Period 2001-2010, 114 patients: 100% of SL, 90% of OL, and 81% of NL patients were in Engel’s class I or II. Both TLE and extratemporal (ETLE) SL patients obtained a 100% seizure control. Among the OL patients, 95% with TLE and 43% of ETLE achieved seizure control. In the NL group, the percentages were 88% in TLE, and 50% in ETLE. Conclusions. In our series, SL was a predictor of a favorable outcome. In TLE patients, good results were achieved despite normal MRI. Patients with ETLE and NL did not have a worse outcome than those with OL. A classification in SL, OL and NL seems more helpful for predicting the surgical outcome than the traditional classification lesion versus non-lesion MRI. Radiological findings must be carefully evaluated in the context of a complete epilepsy surgery evaluation (AU)

Dumbbell-Shaped Epidural Capillary Hemangioma Presenting as a Lung Mass: Case Report and Review of the Literature.

STUDY DESIGN: A case report and literature review. OBJECTIVE: We present the fourth case of a spinal epidural capillary hemangioma with a dumbbell-shaped appearance in the magnetic resonance image reported in the literature and the second presented as a lung mass. SUMMARY OF BACKGROUND DATA: Hemangiomas are congenital vascular malformations that pathologists frequently consider to be hamartomatous malformations. Hemangiomas of the spine are usually lesions of the vertebral bodies, but they can sit in other locations such as the intramedullary or epidural space. Purely epidural hemangiomas are rare and most of them are of cavernous type. METHODS: We present a 67-year-old female with a thoracic dumbbell-shaped capillary hemangioma with both foraminal and intrathoracic extensions, whose presentation was pleural effusion associated with mediastinal mass suggestive of pulmonary neoplasia. Surgical treatment consisted of total removal en bloc of the lesion. RESULTS: Microscopic evaluation showed a fibrofatty tissue with a proliferation of vascular structures that were generally of a small size, with areas of myxoid appearance. To date, there have been 8 epidural capillary hemangiomas of the thoracic and lumbar spine reported in the literature, and only 3 of them were dumbbell-shaped with extraforaminal extension. CONCLUSION: It is important to consider the diagnosis of hemangiomas in the differential diagnosis of epidural lesions with dumbbell-shaped appearance in the magnetic resonance image, especially at the thoracic level. It is a benign and potentially curable disease and the most appropriate surgical treatment is en bloc resection of the entire lesion. They are usually presented as a progressive myelopathy, so early treatment may prevent permanent neurological deficits. LEVEL OF EVIDENCE: 5.

Deep brain stimulation of the centromedian thalamic nucleus for the treatment of generalized and frontal epilepsies.

PURPOSE: Deep brain stimulation (DBS) of the thalamus is an emerging surgical option for people with medically refractory epilepsy that is not suitable for resective surgery, or in whom surgery has failed. Our main aim was to evaluate the efficacy of bilateral centromedian thalamic nucleus (CMN) DBS for seizure control in generalized epilepsy and frontal lobe epilepsy with a two-center, single-blind, controlled trial. METHODS: Participants were adults with refractory generalized or frontal lobe epilepsy. Seizure diaries were kept by patients/carers prospectively from enrollment. The baseline preimplantation period was followed by a control period consisting of a blind stimulation-OFF phase of at least 3 months, a 3-month blind stimulation-ON phase, and a 6-month unblinded stimulation-ON phase. The control period was followed by an unblinded long-term extension phase with stimulation-ON in those patients in whom stimulation was thought to be effective. KEY FINDINGS: Eleven patients were recruited at King's College Hospital (London, United Kingdom United Kingdom) and at University Hospital La Princesa (Madrid, Spain). Among the five patients with frontal lobe epilepsy, only one patient had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, two patients with frontal lobe epilepsy had >50% improvement in seizure frequency. All six patients with generalized epilepsy had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, five of the six patients showed >50% improvement in the frequency of major seizures (one became seizure free, one had >99% improvement, and three had 60-95% reduction in seizure frequency). Among patients with generalized epilepsy, the DBS implantation itself appears to be effective, as two patients remained seizure free during 12 and 50 months with DBS OFF, and the remaining four had 50-91% improvement in the initial 3 months with DBS OFF. SIGNIFICANCE: DBS implantation and stimulation of the CMN appears to be a safe and efficacious treatment, particularly in patients with refractory generalized epilepsy. CMN stimulation was not as effective in frontal lobe epilepsy, which requires further studies. DBS of the CMN should be considered as a treatment option, particularly in patients with refractory generalized epilepsy syndromes.

[Vagus nerve stimulation in patients with migraine]. / Estimulacion del nervio vago en pacientes migrañosos.

INTRODUCTION: Vagus nerve stimulation (VNS) has been approved for the treatment of refractory epilepsy when resective surgery is not possible, and has proved to be highly effective. Series published in the literature suggest a beneficial effect of VNS in the treatment of migraine. AIMS: To determine the degree to which headaches improve in patients with migraine after the placement of VNS to treat refractory epilepsy, and to evaluate what variables are associated with an increased chance of success with this measure. PATIENTS AND METHODS: An observation-based retrospective study was conducted from 1st January 1999 until 31st December 2010. Patients with VNS for refractory epilepsy were contacted by telephone, after selecting those who fulfilled International Headache Society criteria for migraine. Data collected included age, gender, year of placement, age at onset of epilepsy and migraine, improvement of seizures and migraine, presence of migraine with aura and coexistence of anxious-depressive syndrome. Ninety-four patients with VNS were contacted and 13 patients with migraine were selected. RESULTS: Following placement of the VNS, the number of episodes of migraine was seen to decrease by at least 50% in nine patients (69%) (p = 0.004) and there was a drop in the number of episodes of migraine in those patients who had also reduced their epileptic seizures (p = 0.012). No statistically significant associations were observed as regards sex, age, length of disease history, existence of migraine with aura or coexistence of anxious-depressive syndrome. CONCLUSIONS: VNS could have beneficial effects for patients with migraine, especially in cases that are difficult to control. Due to the type of study, these conclusions must be taken with caution. Prospective clinical studies are needed before introducing the technique into daily clinical practice.

TITLE: Estimulacion del nervio vago en pacientes migrañosos.Introduccion. La estimulacion del nervio vago (ENV) esta aprobada para el tratamiento de la epilepsia refractaria cuando no es posible cirugia resectiva, con una eficacia bien establecida. Series publicadas sugieren un efecto beneficioso de la ENV en la migraña. Objetivos. Determinar el grado de mejoria de la cefalea en pacientes migrañosos a los que se les habia implantado una ENV para tratamiento de la epilepsia refractaria y evaluar que variables se asocian a mayor posibilidad de exito con esta medida. Pacientes y metodos. Estudio observacional y retrospectivo desde el 1 de enero de 1999 hasta el 31 de diciembre de 2010. Se contacto telefonicamente con los pacientes con ENV para epilepsia refractaria, seleccionando a aquellos que cumplian los criterios de la Sociedad Internacional de Cefaleas para la migraña. Se recogieron edad, genero, año de implantacion, edad de inicio de la epilepsia y la migraña, mejoria de crisis y de migraña, presencia de aura migrañosa y coexistencia de sindrome ansiosodepresivo. Se contacto con 94 pacientes con ENV y se selecciono a 13 pacientes migrañosos. Resultados. Tras la implantacion de la ENV, se observo una disminucion de al menos el 50% de los episodios de migraña en nueve pacientes (69%) (p = 0,004), asi como una disminucion del numero de episodios de migraña en aquellos pacientes que tambien habian reducido sus crisis epilepticas (p = 0,012). No se observaron asociaciones estadisticamente significativas en cuanto al sexo, edad, tiempo de evolucion, existencia de aura migrañosa o coexistencia de sindrome ansiosodepresivo. Conclusiones. La ENV podria resultar beneficiosa en pacientes con migraña, especialmente en casos de dificil control. Debido al tipo estudio, hay que tomar estas conclusiones con precaucion. Seran necesarios estudios clinicos prospectivos antes de llevarse a la practica clinica habitual.

Estimulación del nervio vago en pacientes migrañosos / Vagus nerve stimulation in patients with migraine

Introducción. La estimulación del nervio vago (ENV) está aprobada para el tratamiento de la epilepsia refractaria cuando no es posible cirugía resectiva, con una eficacia bien establecida. Series publicadas sugieren un efecto beneficioso de la ENV en la migraña. Objetivos. Determinar el grado de mejoría de la cefalea en pacientes migrañosos a los que se les había implantado una ENV para tratamiento de la epilepsia refractaria y evaluar qué variables se asocian a mayor posibilidad de éxito con esta medida. Pacientes y métodos. Estudio observacional y retrospectivo desde el 1 de enero de 1999 hasta el 31 de diciembre de 2010. Se contactó telefónicamente con los pacientes con ENV para epilepsia refractaria, seleccionando a aquéllos que cumplían los criterios de la Sociedad Internacional de Cefaleas para la migraña. Se recogieron edad, género, año de implantación, edad de inicio de la epilepsia y la migraña, mejoría de crisis y de migraña, presencia de aura migrañosa y coexistencia de síndrome ansiosodepresivo. Se contactó con 94 pacientes con ENV y se seleccionó a 13 pacientes migrañosos. Resultados. Tras la implantación de la ENV, se observó una disminución de al menos el 50% de los episodios de migraña en nueve pacientes (69%) (p = 0,004), así como una disminución del número de episodios de migraña en aquellos pacientes que también habían reducido sus crisis epilépticas (p = 0,012). No se observaron asociaciones estadísticamente significativas en cuanto al sexo, edad, tiempo de evolución, existencia de aura migrañosa o coexistencia de síndrome ansiosodepresivo. Conclusiones. La ENV podría resultar beneficiosa en pacientes con migraña, especialmente en casos de difícil control. Debido al tipo estudio, hay que tomar estas conclusiones con precaución. Serán necesarios estudios clínicos prospectivos antes de llevarse a la práctica clínica habitual (AU)

Introduction. Vagus nerve stimulation (VNS) has been approved for the treatment of refractory epilepsy when resective surgery is not possible, and has proved to be highly effective. Series published in the literature suggest a beneficial effect of VNS in the treatment of migraine. Aims. To determine the degree to which headaches improve in patients with migraine after the placement of VNS to treat refractory epilepsy, and to evaluate what variables are associated with an increased chance of success with this measure. Patients and methods. An observation-based retrospective study was conducted from 1st January 1999 until 31st December 2010. Patients with VNS for refractory epilepsy were contacted by telephone, after selecting those who fulfilled International Headache Society criteria for migraine. Data collected included age, gender, year of placement, age at onset of epilepsy and migraine, improvement of seizures and migraine, presence of migraine with aura and coexistence of anxious-depressive syndrome. Ninety-four patients with VNS were contacted and 13 patients with migraine were selected. Results. Following placement of the VNS, the number of episodes of migraine was seen to decrease by at least 50% in nine patients (69%) (p = 0.004) and there was a drop in the number of episodes of migraine in those patients who had also reduced their epileptic seizures (p = 0.012). No statistically significant associations were observed as regards sex, age, length of disease history, existence of migraine with aura or coexistence of anxious-depressive syndrome. Conclusions. VNS could have beneficial effects for patients with migraine, especially in cases that are difficult to control. Due to the type of study, these conclusions must be taken with caution. Prospective clinical studies are needed before introducing the technique into daily clinical practice (AU)

Long-term results of posteromedial hypothalamic deep brain stimulation for patients with resistant aggressiveness.

OBJECT: Erethism describes severe cases of unprovoked aggressive behavior, usually associated with some degree of mental impairment and gross brain damage. The etiology can be epileptic, postencephalitic, or posttraumatic, or the condition can be caused by brain malformations or perinatal insults. Erethism is often refractory to medication, and patients must often be interned in institutions, where they are managed with major restraining measures. The hypothalamus is a crucial group of nuclei that coordinate behavioral and autonomic responses and play a central role in the control of aggressive behavior. Deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH) has been proposed as a treatment for resistant erethism, although experience with this treatment around the world is scarce. The objective of this study was to examine the long-term outcome of PMH DBS in 6 patients with severe erethism treated at the authors' institution. METHODS: Medical records of 6 patients treated with PMH DBS for intractable aggressiveness were reviewed. The therapeutic effect on behavior was assessed by the Inventory for Client and Agency Planning preoperatively and at the last follow-up visit. RESULTS: Two patients died during the follow-up period due to causes unrelated to the neurosurgical treatment. Five of 6 patients experienced a significant reduction in aggressiveness (the mean Inventory for Client and Agency Planning general aggressiveness score was -47 at baseline and -25 at the last follow-up; mean follow-up 3.5 years). Similar responses were obtained with low- and high-frequency stimulation. In 4 cases, the patients' sleep patterns became more regular, and in 1 case, binge eating and polydipsia ceased. One of the 3 patients who had epilepsy noticed a 30% reduction in seizure frequency. Another patient experienced a marked sympathetic response with high-frequency stimulation during the first stimulation trial, but this subsided when stimulation was set at low frequency. A worsening of a previous headache was noted by 1 patient. There were no other side effects. CONCLUSIONS: In this case series, 5 of 6 patients with pathological aggressiveness had a reduction of their outbursts of violence after PMH DBS, without significant adverse effects. Prospective controlled studies with a larger number of patients are needed to confirm these results.

Long-term results of vagal nerve stimulation for adults with medication-resistant epilepsy who have been on unchanged antiepileptic medication.

PURPOSE: Several studies suggest that vagal nerve stimulation (VNS) is an effective treatment for medication-resistant epileptic patients, although patients' medication was usually modified during the assessment period. The purpose of this prospective study was to evaluate the long-term effects of VNS, at 18 months of follow-up, on epileptic patients who have been on unchanged antiepileptic medication. METHODS: Forty-three patients underwent a complete epilepsy preoperative evaluation protocol, and were selected for VNS implantation. After surgery, patients were evaluated on a monthly basis, increasing stimulation 0.25mA at each visit, up to 2.5mA. Medication was unchanged for at least 18 months since the stimulation was started. The outcome was analysed in relation to patients' clinical features, stimulation parameters, epilepsy type, magnetic resonance imaging (MRI) results, and history of prior brain surgery. RESULTS: Of the 43 operated patients, 63% had a similar or greater than 50% reduction in their seizure frequency. Differences in the responder rate according to stimulation intensity, age at onset of epilepsy, duration of epilepsy before surgery, previous epilepsy surgery and seizure type, did not reach statistical significance. Most side effects were well tolerated. CONCLUSIONS: 62.8% of our series of 43 medication-resistant epileptic patients experienced a significant long-term seizure reduction after VNS, even in a situation of on unchanged medical therapy. Patient characteristics predictive of VNS responsiveness remain subject to investigation. Controlled studies with larger sample sizes, on VNS for patients with medication-resistant epilepsy on unchanged medication, are necessary to confirm VNS efficacy for drug-resistant epilepsy, and to identify predictive factors.

[Primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors: Group for the Study of Functional-Sterotactic Neurosurgery of The Spain Society of Neurosurgery recommendations]. / Control de las crisis epilépticas durante el postoperatorio inmediato de los tumores cerebrales supratentoriales: recomendaciones del Grupo de Neurocirugía Funcional y Estereotáctica de la Sociedad Española de Neurocirugía.

Our review of the literature is basically focused on the primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors, with the aim of suggesting several recommendations in medical antiepileptic treatment to avoid this kind of seizures which occur immediately after surgery. In conclusion, it is recommended to provide criteria for prophylaxis of early seizures after surgery of cerebral supratentorial tumors. It́s recommended a one week treatment with antiepileptic drugs in patients who didnt have seizures jet, starting immediately after the surgical treatment. If seizures appear during progress of the disease, a large period treatment will be needed. Preferred antiepileptic treatment is intravenous and with a low interactions profile. Levetiracetam, followed by valproic acid seem to be most appropriated drugs due to their properties and protective effects, particularly for our patients requirements. These recommendations are considered a general proposal to effective clinical management of early seizures after surgery, not taking into account the single circumstances of our patients. Always, clinical features of the patients could modify even significantly these guides in the benefit of each patient.

Control de las crisis epilépticas durante el postoperatorio inmediato de los tumores cerebrales supratentoriales: recomendaciones del Grupo de Neurocirugía Funcional y Estereotáctica de la Sociedad Española de Neurocirugía / Primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors: Group for the Study of Functional-Sterotactic Neurosurgery of The Spain Society of Neurosurgery recommendations

Con la finalidad de proponer una serie de recomendaciones del tratamiento médico antiepiléptico, en el perioperatorio de los tumores cerebrales supratentoriales, se realiza una revisión de la literatura enfocada sobre todo a la profilaxis primaria de las crisis epilépticas precoces acaecidas en el postoperatorio inmediato. Se concluye que es recomendable pautar profilaxis primaria antiepiléptica poscirugía durante una semana en los pacientes con tumor cerebral supratentorial que no han presentado crisis epilépticas. Si las crisis aparecen durante la evolución de la enfermedad, es necesario pautar un tratamiento a largo plazo. Dadas las características de estos pacientes, se recomienda usar un fármaco antiepiléptico con presentación por vía intravenosa y un perfil bajo de interacciones. El levetiracetam, seguido del valproato, parecen ser los más adecuados. Dichas recomendaciones deben considerarse como una guía general de manejo, pudiendo ser modificadas, incluso de manera significativa, por las circunstancias propias de cada caso clínico (AU)

Our review of the literature is basically focused on the primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors, with the aim of suggesting several recommendations in medical antiepileptic treatment to avoid this kind of seizures which occur immediately after surgery. In conclusion, it is recommended to provide criteria for prophylaxis of early seizures after surgery of cerebral supratentorial tumors. It's recommended a one week treatment with antiepileptic drugs in patients who didn't have seizures jet, starting immediately after the surgical treatment. If seizures appear during progress of the disease, a large period treatment will be needed. Preferred antiepileptic treatment is intravenous and with a low interactions profile. Levetiracetam, followed by valproic acid seem to be most appropriated drugs due to their properties and protective effects, particularly for our patients requirements. These recommendations are considered a general proposal to effective clinical management of early seizures after surgery, not taking into account the single circumstances of our patients. Always, clinical features of the patients could modify even significantly these guides in the benefit of each patient (AU)