RESUMEN

A woman in her 30s with medically intractable epilepsy and Lennox-Gastaut Syndrome on multiple antiseizure medications and with a deep brain stimulator presented to the epilepsy monitoring unit with increased seizure frequency. She was noted to have periods of apparent apnoea time linked to bursts of epileptiform activity on continuous video EEG monitoring. Once the clinical seizures were controlled, she was discharged to the sleep laboratory. She was noted to have obstructive and central sleep apnoea, which improved with the use of positive airway pressure. Central sleep apnoeas were time linked to electrographic seizures. Ictal central apnoea can easily be overlooked and is likely more common than currently recognised in patients with epilepsy. Ictal central apnoea may be a biomarker for sudden unexpected death in epilepsy.

Asunto(s)

Epilepsia Refractaria , Epilepsia , Apnea Central del Sueño , Apnea , Muerte Súbita , Epilepsia Refractaria/complicaciones , Epilepsia Refractaria/terapia , Electroencefalografía , Epilepsia/complicaciones , Femenino , Humanos , Convulsiones , Apnea Central del Sueño/complicaciones , Apnea Central del Sueño/diagnóstico

RESUMEN

OBJECTIVE: To evaluate current clinical practices and evidence-based literature to establish preliminary recommendations for the management of adults using ketogenic diet therapies (KDTs). METHODS: A 12-topic survey was distributed to international experts on KDTs in adults consisting of neurologists and dietitians at medical institutions providing KDTs to adults with epilepsy and other neurologic disorders. Panel survey responses were tabulated by the authors to determine the common and disparate practices between institutions and to compare these practices in adults with KDT recommendations in children and the medical literature. Recommendations are based on a combination of clinical evidence and expert opinion regarding management of KDTs. RESULTS: Surveys were obtained from 20 medical institutions with >2,000 adult patients treated with KDTs for epilepsy or other neurologic disorders. Common side effects reported are similar to those observed in children, and recommendations for management are comparable with important distinctions, which are emphasized. Institutions differ with regard to recommended biochemical assessment, screening, monitoring, and concern for long-term side effects, and further investigation is warranted to determine the optimal clinical management. Differences also exist between screening and monitoring practices among adult and pediatric providers. CONCLUSIONS: KDTs may be safe and effective in treating adults with drug-resistant epilepsy, and there is emerging evidence supporting the use in other adult neurologic disorders and general medical conditions as well. Therefore, expert recommendations to guide optimal care are critical as well as further evidence-based investigation.

RESUMEN

OBJECTIVE: This study evaluates the efficacy of a modified ketogenic diet (MKD) on seizure frequency, severity, and quality of life (QOL), as well as potential complications of MKD therapy among adults with drug-resistant epilepsy (DRE). METHODS: Changes in seizure frequency, severity, QOL, and side effects were retrospectively examined among adults, ≥17 years of age, with DRE (≥2 antiepileptic drugs [AEDs]), after 3 months of MKD therapy. Attention was paid to medication or vagus nerve stimulator (VNS) changes as well to evaluate potential confounders. RESULTS: A total of 60% (n = 33) of the 55 individuals reported ≥50% seizure frequency improvement, 42 (76%) reported improvement in seizure severity, and 48 (87%) reported improvement in QOL. More patients following a modified ketogenic diet - 15 g net carbohydrate daily (MKD-15) (95%) compared with a MKD-50 (69%) reported improvement in QOL (p = 0.02). Weight among the entire sample declined from 77.5 (20) kg to 73.9 (19.0) kg (p < 0.0001), and total cholesterol (TC), low density lipoprotein (LDL), and total cholesterol:high density lipoprotein (TC:HDL) increased significantly (p = 0.03, p = 0.04, and p = 0.02, respectively). Free carnitine values were available for a select number of patients, 26 (47%) at baseline, and 7 (13%) at follow-up, of which 8 (31%) at baseline, and 2 (29%) at follow-up had carnitine deficiency (<25 nmol/mL). Constipation was noted in 5 patients (9%), and no kidney stones were reported during the study period. There were no statistical differences in number or dose changes for AED or VNS during the study period. SIGNIFICANCE: Modified ketogenic diet therapies reduce seizure frequency and severity and improve QOL among adults with DRE with few side effects outside of weight loss, a desired outcome among many adults with DRE. More restrictive MKDs may offer improved seizure severity and QOL. Modified ketogenic diet therapy increases LDL cholesterol, which may be cardioprotective if related to an increase in LDL particle size with high saturated fat intake; however, more research is needed examining LDL particle size changes among those receiving MKD therapy.

Asunto(s)

Dieta Cetogénica/métodos , Epilepsia Refractaria/dietoterapia , Epilepsia Refractaria/psicología , Calidad de Vida/psicología , Convulsiones/dietoterapia , Convulsiones/psicología , Adolescente , Adulto , Niño , Dieta Baja en Carbohidratos/métodos , Epilepsia Refractaria/diagnóstico , Femenino , Humanos , Masculino , Estudios Retrospectivos , Convulsiones/diagnóstico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento

RESUMEN

OBJECTIVE: Adults with drug-resistant epilepsy (DRE) are among the most challenging to treat. This study assessed whether specific subpopulations of adult patients with refractory epilepsy responded differently to modified ketogenic diet (MKD) therapy. METHODS: Changes in seizure frequency, severity, and quality of life (QOL) were retrospectively analyzed based on pre-MKD surgical history, type of epilepsy, imaging findings, and vagal nerve stimulation (VNS) history among adults, ≥17 years of age, with DRE, receiving MKD therapy for three months. Additionally, particular attention was made to medication and VNS adjustments. RESULTS: Responder rates in seizure frequency, severity, and QOL reported among those with prior surgery were 56%, 75%, and 94%, respectively. Among those with focal epilepsy: 57%, 76%, and 76% had improvements in seizure frequency, seizure severity, and QOL, respectively whereas 83% improvement was seen for all three measures in those with generalized epilepsy. Among those with abnormal imaging: just over 50% reported improvements on all measures. For those with VNS, 53%, 63%, and 95% had improvements in seizure frequency, seizure severity, and QOL, respectively. No statistical differences in seizure frequency, severity, or QOL were noted between groups based on prediet surgical history, seizure type, imaging abnormalities, or VNS history. Compared with expected improvement from medication adjustment alone, significant improvement was seen for all groups; notably, the Z-test for proportions for the surgery group, when compared with placebo responder rates at 20%, was 3.6, p < 0.001. CONCLUSIONS: Modified ketogenic diet therapies are effective in improving seizure frequency, severity, and QOL and may offer the best chance for improvement among those whose seizures have persisted despite surgical intervention and VNS therapy. All types of epilepsy respond to MKDs, and possibly those with generalized epilepsy may respond better.

Asunto(s)

Dieta Cetogénica/métodos , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/dietoterapia , Vigilancia de la Población , Estimulación del Nervio Vago/métodos , Adolescente , Adulto , Anciano , Dieta Cetogénica/tendencias , Epilepsia Refractaria/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Estimulación del Nervio Vago/tendencias , Adulto Joven

RESUMEN

OBJECTIVE The purpose of this study was to assess the positive predictive value of postresection outcomes obtained by presurgical subtracted ictal SPECT in patients with lesional (MRI positive) and nonlesional (MRI negative) refractory extratemporal lobe epilepsy (ETLE) and temporal lobe epilepsy (TLE). Specifically, outcomes were compared between partial versus complete resection of the regions of transient hyperperfusion identified using subtraction ictal SPECT coregistered to MRI (SISCOM) in relation to the ictal onset zone (IOZ) that was confirmed by electrocorticography (ECoG). That is, SISCOM was used to understand the long-term postsurgical outcomes following resection of the IOZ that overlapped with 1 or more regions of ictal onset-associated transient hyperperfusion. METHODS The study cohort included 44 consecutive patients with refractory ETLE or TLE who were treated between 2002 and 2013 and underwent presurgical evaluation using SISCOM. Concordance was determined between SISCOM localization and the IOZ on the basis of ECoG monitoring. In addition, the association between the extent of the resection site overlapping with the SISCOM signal and postresection outcomes were assessed. Postsurgical follow-up was longer than 24 months in 39 of 44 patients. RESULTS The dominant SISCOM signals were concordant with ECoG and overlapped the resection site in 32 of 44 (73%) patients (19 ETLE and 13 TLE patients), and 20 of 32 (63%) patients became seizure free. In all 19 ETLE patients with concordant SISCOM and ECoG results, the indicated location of ictal onset on ECoG was completely resected; 11 of 19 patients (58%) became seizure free (Engel Class I). In all 13 TLE patients with concordant SISCOM and ECoG results, the indicated ECoG focus was completely resected; 9 of 13 patients (69%) became seizure free (Engel Class I). Complete resection of the SISCOM signal was found in 7 of 34 patients (21%). Of these 7 patients, 5 patients (72%) were seizure free (Engel Class I). Partial resection of the SISCOM signal was found in 16 of 34 patients (47%), and 10 of these 16 patients (63%) were seizure free (Engel Class I) after more than 24 months of follow-up. CONCLUSIONS Concordance between 1 or more SISCOM regions of hyperperfusion with ECoG and at least partial resection of the dominant SISCOM signal in this refractory epilepsy cohort provided additional useful information for predicting long-term postresection outcomes. Such regions are likely critical nodes in more extensive, active, epileptogenic circuits. In addition, SPECT scanner technology may limit the sensitivity of meaningful SISCOM signals for identifying the maximal extent of the localizable epileptogenic network.

Asunto(s)

Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/cirugía , Imagen por Resonancia Magnética , Procedimientos Neuroquirúrgicos/métodos , Cirugía Asistida por Computador , Tomografía Computarizada de Emisión de Fotón Único , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Cuidados Preoperatorios , Estudios Retrospectivos , Adulto Joven

RESUMEN

BACKGROUND: There have been only a few large series that have used a tailored temporal lobectomy. OBJECTIVE: To clarify whether tailoring a temporal lobe resection will lead to equivalent epilepsy outcomes or have the same predictive factors for success when compared with standard resections. METHODS: Retrospective analysis of 222 patients undergoing a tailored temporal lobe resection. Demographic measures and typical factors influencing outcome were evaluated. RESULTS: Pathology included 222 cases. With a mean follow-up of 5.4 years, 70% of patients achieved Engel class I outcome. A significant factor predicting Engel class I outcome on multivariate analysis was lesional pathology (P = .04). Among patients with hippocampal sclerosis, extent of lateral neocortical resection and hippocampal resection were not statistically associated with Engel class I outcome (P = .93 and P = .24). However, an analysis of Engel class subgroups a to d showed that patients who had a complete hippocampectomy in the total series were more likely to achieve an Engel class Ia outcome (P = .04). This was also true among patients with hippocampal sclerosis (P = .03). Secondarily, generalized seizure (P = .01) predicted outcome less than Engel class I. Predictive of poor outcome was the need for preoperative electrodes (P = .02). Complications included superior quadrant visual field defects, 2 cases of permanent dysphasia, and 3 wound infections. CONCLUSION: Predictors of successful seizure outcome for a tailored temporal lobectomy are similar to standard lobectomy. Patients with secondarily generalized epilepsy and cases in which preoperative subdural electrodes were thought necessary were less likely to achieve class I outcome. Among Engel class I cases, those who had a complete hippocampectomy were more likely to achieve Engel class Ia outcome.

Asunto(s)

Lobectomía Temporal Anterior/métodos , Epilepsia del Lóbulo Temporal/cirugía , Lóbulo Temporal/cirugía , Adulto , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

A novel depth electrode placement planning strategy is presented for propagating current to distant epileptic tissue during direct neurostimulation therapy. Its goal is to predict optimal lead placement in cortical white matter for influencing the maximal extent of the epileptic circuit. The workflow consists of three fundamental techniques to determine responsive neurostimulation depth lead placement in a patient with bilaterally independent temporal lobe epileptogenic regions. (1) Pre-implantation finite element modeling was used to predict the volume of cortical activation (VOCA). This model estimated the electric field and neural tissue influenced surrounding two adjacent active depth contacts prior to implantation. The calculations included anticipated stimulation parameters. (2) Propagation of stimulation therapy was simulated pre-implantation using the VOCA model positioned in the subject's diffusion tensor imaging (DTI) determined 8h post-ictally compared to an interictal DTI. (3) Validation of the predicted stimulated anatomical targets was determined 4.3 months post-implantation using subtracted activated SPECT (SAS). Presurgically, the modeling system predicted white matter connectivity and visual side-effects to stimulation. Post-implantation, SAS validated focal blood flow changes in ipsilateral occipital and frontal regions, and contralateral temporal lobe. This workflow demonstrates the feasibility of planning white matter-electrode placement with individual specificity to predict propagation of electrical current throughout an epileptic circuit.

Asunto(s)

Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/terapia , Neuroestimuladores Implantables , Fibras Nerviosas Mielínicas/fisiología , Imagen de Difusión Tensora/métodos , Epilepsia del Lóbulo Temporal/diagnóstico , Estudios de Factibilidad , Femenino , Humanos , Valor Predictivo de las Pruebas , Adulto Joven

RESUMEN

Epilepsy surgery treatment should be considered as standard of care for all patients with medically intractable partial-onset epilepsy who are found to be good surgical candidates based on their presurgical evaluation. Delaying surgical treatment continues to be a problem among neurologists. The early recognition of pharmacoresistance and patients' referral for presurgical evaluation can shorten the time to identify potential surgical candidates. A successful early surgery can be expected to significantly improve these patients' quality of life, not only because of a seizure-free state but also by improving psychiatric comorbidities. Vagal nerve stimulation (VNS) is currently the only FDA-approved neurostimulation treatment strategy for patients who are not considered candidates for epilepsy surgery. VNS has been shown to decrease seizure frequency by approximately 50% in 30 to 40% of implanted patients. The future of epilepsy surgery and neurostimulation for those individuals with medically intractable partial-onset epilepsy shows great promise.

Asunto(s)

Terapia por Estimulación Eléctrica/normas , Epilepsia/cirugía , Epilepsia/terapia , Procedimientos Neuroquirúrgicos/normas , Nervio Vago/fisiología , Resistencia a Medicamentos/fisiología , Diagnóstico Precoz , Terapia por Estimulación Eléctrica/métodos , Terapia por Estimulación Eléctrica/tendencias , Electrodos Implantados/normas , Servicios Médicos de Urgencia/normas , Humanos , Neurología/normas , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/tendencias , Resultado del Tratamiento

RESUMEN

BACKGROUND: This is a technical report describing a different technique for the insertion of epidural electrodes in the preoperative evaluation of epilepsy surgery. Our experience in 67 cases using this technique is analyzed. METHODS: Cylinder electrodes with multiple recording nodes spaced 1 cm apart along a Silastic core are placed into the epidural space under general anesthesia through single or multiple burr holes. We reviewed the data on 67 cases of medically intractable epilepsy requiring intracranial monitoring that had epidural cylinder electrodes placed. The electrodes were placed bilaterally or contralateral to subdural grids in 64 of the 67 cases. Continuous monitoring was performed from 1 to 3 weeks. RESULTS: This method was most useful when used bilaterally or contralateral to subdural grids. Definitive surgery was rendered in 48 of 67 cases. After monitoring, all electrodes were removed at bedside or upon return to the operating room for definitive surgery. There were no mortalities, infections, cerebrospinal fluid leaks, neurologic deficits, or electrode malfunctions. Two patients (2/67, 3%) did develop subdural hematomas early in our series after dural injury near the pterion; however, these patients did not sustain permanent deficit. CONCLUSIONS: Epidural cylinders are another option for preoperative monitoring, useful for determining lobe or laterality of seizure genesis. They offer an alternate method to EPEs in cases where epidural recording is desirable. The cylinder electrodes are easy to place and can be removed without a return to the operating theater. The electrodes' minimal mass effect allows them to be safely placed bilaterally or contralateral to subdural grids. The epidural cylinders can monitor cortex with a greater density of nodes and can access regions not amenable to EPEs.

Asunto(s)

Electrodiagnóstico/instrumentación , Espacio Epidural/fisiología , Epilepsia/diagnóstico , Epilepsia/cirugía , Monitoreo Fisiológico/instrumentación , Cuidados Preoperatorios/instrumentación , Adolescente , Adulto , Corteza Cerebral/anatomía & histología , Corteza Cerebral/fisiología , Corteza Cerebral/cirugía , Niño , Preescolar , Craneotomía , Electrodos/normas , Electrodiagnóstico/métodos , Espacio Epidural/anatomía & histología , Espacio Epidural/cirugía , Epilepsia/fisiopatología , Femenino , Humanos , Complicaciones Intraoperatorias/prevención & control , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Procedimientos Neuroquirúrgicos/instrumentación , Procedimientos Neuroquirúrgicos/métodos , Cuidados Preoperatorios/métodos

RESUMEN

The use of antiepileptic drugs (AEDs) in monotherapy is always preferred to a polytherapy regimen because monotherapy facilitates drug compliance, is associated with a lower risk of toxicity, and is less costly. In addition, the yield of polytherapy to render a patient seizure-free when monotherapy regimens did not is relatively low. The available data derived from randomized controlled trials suggest that standard and new AEDs appear to display comparable antiepileptic efficacy but they differ with respect to tolerability and toxicity, which may be related to their pharmacodynamic and pharmacokinetic properties. New AEDs appear to be better tolerated than standard AEDs and to have fewer pharmacokinetic interactions than standard AEDs. In this article, we review the advantages of using AEDs in monotherapy in patients with newly diagnosed and refractory epilepsies, focusing on the individual properties of the drugs that may make them more appropriate in various patient groups.

Asunto(s)

Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Factores de Edad , Anticonvulsivantes/farmacocinética , Ensayos Clínicos como Asunto/tendencias , Relación Dosis-Respuesta a Droga , Resistencia a Medicamentos/fisiología , Quimioterapia Combinada , Epilepsia/fisiopatología , Humanos , Tasa de Depuración Metabólica/fisiología , Resultado del Tratamiento

RESUMEN

Depression in patients with epilepsy (PWE) is a relatively common comorbidity that has a significant negative impact on their quality of life. Therefore, recognition and management of a comorbid depressive disorder is paramount to achieve successful comprehensive treatment in PWE. Depression in epilepsy may mimic primary depressive disorders, but in a significant percentage of depressed PWE, the clinical semiology has an atypical presentation and fails to meed any of the diagnostic criteria established in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Despite the relatively high prevalence of depression in epilepsy and its frequent atypical presentation, there has been only one controlled study (in 1979) to establish the safety and efficacy of antidepressant drugs in PWE. Accordingly, clinicians must rely on data from studies of pharmacotherapy of primary depression. These data are adequate to guide the clinician in the basic principles of pharmacotherapy of depression in PWE. Many questions are yet to be answered, including: 1) are the expectations of symptom remission to pharmacotherapy in PWE different in typical and atypical forms of depression, and do they differ from those of patients with primary depression? and 2) are the doses of antidepressant drugs necessary to yield symptom remission different between PWE and those patients with primary mood disorders?

RESUMEN

Article abstract Depressive disorders (DDs) are the most common type of psychiatric co-morbidity in patients with epilepsy. They are more likely to occur in patients with partial seizure disorders of temporal and frontal lobe origin and are more frequent among patients with poorly controlled seizures. Despite their relatively high prevalence, DDs remain unrecognized and untreated in a large proportion of patients. This article highlights the evidence of a close association between DDs and epilepsy, beginning with the bi-directional relationship between the two disorders. Not only are patients with epilepsy more likely to experience a DD, but a history of DD preceding the onset of the seizure disorder is more likely to be identified in patients with epilepsy than in a control group. In support of these observations, we review data from animal models of epilepsy showing that decreased activity of serotonin, norepinephrine, dopamine, and GABA facilitate the kindling process of seizure foci, worsen seizure frequency and severity, and are reversed or blocked by antidepressant drugs. Decreased activity of these neurotransmitters is a pivotal pathogenic mechanism of DDs and forms the basis of their pharmacotherapy. Thus, DDs and epilepsy may share common pathogenic mechanisms that facilitate the occurrence of one in the presence of the other. Contrary to long-held beliefs by patients and clinicians alike, in the sense that DDs are a "normal reaction" to the obstacles posed by epilepsy, we review evidence that points to their biologic or endogenous nature. We find a genetic predisposition to DDs, as evidenced by the frequent family history of mood disorders in these patients. Neuroimaging and neuropsychological data support a frontal lobe dysfunction in DDs, and a recent study documents concomitant dysfunction of mesial temporal structures. Depressive disorders have various clinical presentations, some typical of the different types of mood disorders in non-epileptic patients, others constituting rather frequent atypical presentations that can easily go unrecognized. A review of the pharmacologic treatment of DDs in epilepsy highlights the lack of scientific data and points to the empirical form in which these patients have been treated up to the present time. Contrary to clinicians' fears, most antidepressant drugs are safe in patients with epilepsy.

Asunto(s)

Trastorno Depresivo/diagnóstico , Epilepsia/psicología , Comorbilidad , Trastorno Depresivo/fisiopatología , Trastorno Depresivo/psicología , Epilepsia/fisiopatología , Lóbulo Frontal/fisiopatología , Humanos , Pruebas Neuropsicológicas , Neurotransmisores/fisiología , Factores de Riesgo

RESUMEN

Valproate is an antiepileptic drug with a wide spectrum efficacy in the management of various types of seizures and epileptic syndromes. In addition to its efficacy in epilepsy, valproate has been found to have therapeutic effects in various psychiatric disorders, including manic states, bipolar, panic and schizophreniform disorders and in the prevention and acute treatment of migraine. Valproate is available in various formulations that differ primarily in their absorption profiles. The purpose of this review article is to highlight the most important pharmacokinetic and pharmacodynamic properties of this drug that all clinicians should be aware of when using it as an antiepileptic, antimigraine, or mood-stabilizing agent. We review its use with other common antiepileptics or psychotropic drugs and the pharmacokinetic interactions with commonly used drugs. We also review its tolerance and toxicity profile in the various age-groups and devote a section to the particular problems associated with its use in patients with renal and hepatic failure and in women of gestational age.

RESUMEN

Psychosis, irritability, and aggression in persons with epilepsy are frequently the focus of clinical intervention. These neuropsychiatric symptoms may occur due to the bidirectional relationship between psychosis and epilepsy, in which the potential etiopathogenic mechanisms are believed to be closely related to the seizure disorder itself and also may result from underlying brain injury or behavioral intolerance of antiepileptic or other medication. Epileptic patients are at heightened risk for mood disorders, psychotic disorders, and delerium. The possible lowering of seizure threshold by psychotropic drugs should not contraindicate appropriate use of psychotropic agents, and risk may be minimized by the selection of agents not associated with a relatively high likelihood of altering seizure threshold. Behavioral toxicity of antiepileptic drugs (AEDs) is addressed by selection of alternative agents, and some AEDs appear to possess positive psychotropic effects. The use of antipsychotic, antidepressant, and other psychotropic agents in psychosis, irritability, and aggression in epilepsy is discussed, including dosage ranges, major side effects, and potential interactions between antieplieptic and psychotropic medication.