Burden of intractable epilepsy.
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Cost of Illness↗
Biomedical subjects
Samuel Wiebe
Publications and source records attributed to Samuel Wiebe.
Outcome measures in intractable epilepsy.
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Epilepsy↗
Evaluating surgery effectiveness.
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Electroencephalography↗
Occipital epilepsy: lateral versus mesial.
This study compares ictal semiology, neurological examination and scalp EEG between lateral and mesial occipital epilepsy to assess the contribution non-invasive data make in determining the epileptogenic region within an occipital lobe. We assessed seizure origin in 41 occipital patients as lateral (11 patients), mesial (20) and both surfaces (10) as indicated by subdurally recorded seizures (nine), a lesion whose removal reduced seizure quantity by > or =90% (six), or who met both criteria (26). No aspect of semiology distinguished lateral from mesially originating occipital seizures. A pre-operative visual field deficit appeared in eight (42%) out of 19 testable patients with mesial originating seizures, three (30%) out of 10 patients with both surfaces epileptogenic, but none of the 10 testable patients whose seizures arose only from the lateral surface (P = 0.0373, lateral versus mesial and both surfaces). Although occipital seizures appeared on the majority of the first five scalp EEG recordings in four (36%) out of 11 patients with laterally originating occipital seizures compared with none of 20 patients in whom seizures originated mesially (P = 0.0105), no other scalp EEG feature distinguished seizures from these surfaces. We conclude that subdural electroencephalography is likely to be necessary to delineate the epileptogenic region within an occipital lobe. Nonetheless, focally originating scalp-recorded seizures accurately lateralized the epileptogenic zone in 20 (49%) of our 41 patients compared with only one (2%) which originated contralaterally (P = 0.0001). This relationship held when considering only the first five scalp EEGs: the seizures of 10 patients (24%) appeared ipsilaterally and none contralaterally (P = 0.001). Moreover, interictal occipital (01,2) and posterior temporal (T5, T6) spikes appeared consistently and significantly (P < 0.001) more commonly ipsilateral to epileptogenesis than contralateral using multiple methods of analysis.
Adolescent↗
Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis.
Assessment of long-term outcomes is essential in brain surgery for epilepsy, which is an irreversible intervention for a chronic condition. Excellent short-term results of resective epilepsy surgery have been established, but less is known about long-term outcomes. We performed a systematic review and meta-analysis of the evidence on this topic. To provide evidence-based estimates of long-term results of various types of epilepsy surgery and to identify sources of variation in results of published studies, we searched Medline, Index Medicus, the Cochrane database, bibliographies of reviews, original articles and book chapters to identify articles published since 1991 that contained > or =20 patients of any age, undergoing resective or non-resective epilepsy surgery, and followed for a mean/median of > or =5 years. Two reviewers independently assessed study eligibility and extracted data, resolving disagreements through discussion. Seventy-six articles fulfilled our eligibility criteria, of which 71 reported on resective surgery (93%) and five (7%) on non-resective surgery. There were no randomized trials and only six studies had a control group. Some articles contributed more than one study, yielding 83 studies of which 78 dealt with resective surgery and five with non-resective surgery. Forty studies (51%) of resective surgery referred to temporal lobe surgery, 25 (32%) to grouped temporal and extratemporal surgery, seven (9%) to frontal surgery, two (3%) to grouped extratemporal surgery, two (3%) to hemispherectomy, and one (1%) each to parietal and occipital surgery. In the non-resective category, three studies reported outcomes after callosotomy and two after multiple subpial transections. The median proportion of long-term seizure-free patients was 66% with temporal lobe resections, 46% with occipital and parietal resections, and 27% with frontal lobe resections. In the long term, only 35% of patients with callosotomy were free of most disabling seizures, and 16% with multiple subpial transections remained free of all seizures. The year of operation, duration of follow-up and outcome classification system were most strongly associated with outcomes. Almost all long-term outcome studies describe patient cohorts without controls. Although there is substantial variation in outcome definition and methodology among the studies, consistent patterns of results emerge for various surgical interventions after adjusting for sources of heterogeneity. The long-term (> or =5 years) seizure free rate following temporal lobe resective surgery was similar to that reported in short-term controlled studies. On the other hand, long-term seizure freedom was consistently lower after extratemporal surgery and palliative procedures.
Adolescent↗
Sudden unexpected death in epilepsy: evidence-based analysis of incidence and risk factors.
PURPOSE: To provide an evidence-based analysis of the risk factors and incidence of SUDEP, and to assess methodological aspects and sources of variation in studies dealing with SUDEP. METHODS: An expert in library resources and electronic databases comprehensively searched Medline, Index Medicus, and the Cochrane library. We included case-control or cohort studies focusing on SUDEP in children or adults, published in the English language. Two reviewers independently applied study eligibility criteria and extracted data, resolving disagreements through discussion. RESULTS: Of 404 citations identified, 83 potentially eligible articles were reviewed in full text and 36 studies fulfilled eligibility criteria (29 cohort and 8 case-control studies). In studies using non-SUDEP deaths as controls the most consistent risk factors were a seizure preceding death, and subtherapeutic antiepileptic drug levels. In studies that used persons living with epilepsy as controls the main risk factors for SUDEP were youth, high seizure frequency, high number of antiepileptic drugs and long duration of epilepsy. The annual incidence of SUDEP ranged from 0 to 10:1000. It was highest in studies of candidates for epilepsy surgery and epilepsy referral centers (2.2:1000-10:1000), intermediate in studies including patients with mental retardation (3.4:1000-3.6:1000), and lowest in children (0-0.2:1000). The incidence was similar in autopsy series (0.35:1000-2.5:1000) and in studies of epilepsy patients in the general population (0-1.35:1000). The median proportion of SUDEP in relation to overall mortality in epilepsy was 40 and 4% in high- and low-risk groups, respectively. CONCLUSIONS: Although studies on SUDEP are heterogeneous in methodology, consistent patterns in incidence and risk factors emerge. Low- and high-risk patient groups are identified, which determine the relative contribution of SUDEP to overall mortality in epilepsy. In addition to patient population, risk factors for SUDEP depend on the type of controls used for comparison (dead versus live patients with epilepsy). Risk factors found in different studies are not necessarily contradictory, but are often complementary.
Case-Control Studies↗
Progress in clinical neurosciences: measuring the benefit of therapies for neurological disorders.
BACKGROUND: Clinicians in the neurosciences need to interpret and apply a growing body of evidence about therapy. METHODS: Using a clinical scenario about painful diabetic neuropathy and evidence about one treatment option, we review the advantages, limitations, and the clinical interpretation of commonly reported measures of effectiveness, emphasizing their application to the care of individual patients. RESULTS: Absolute differences between treatment and control groups (e.g., absolute risk difference) are clinically intuitive and preferable to relative measures (e.g., relative risk). The number needed to treat is particularly useful and clinically applicable. Continuous measures are best interpreted using thresholds of clinically important change, which provide information about the number of patients experiencing meaningful improvement or worsening. CONCLUSIONS: Using simple principles of evidence based care, clinicians can correctly interpret the common measures of treatment effectiveness and apply them to the care of individual patients.
Evidence-Based Medicine↗
The numbers needed to treat for neurological disorders.
BACKGROUND: Numerous therapeutic interventions have been developed in the neurosciences. Clinicians need summary measures about efficacy of therapies that derive from the best available evidence, and that can be readily extrapolated to clinical practice. The number needed to treat (NNT) is intuitive and clinically applicable. We provide clinicians with a single source that summarizes important therapies in the main neurological and neurosurgical areas. METHODS: Critically appraised evidence about therapies in the neurosciences was obtained from meta-analyses in all neurosciences groups in the Cochrane library, and from critically appraised topics at the University of Western Ontario. Therapies were included if they were deemed relevant and if outcomes were dichotomous. For each therapy, we obtained absolute risk differences and their 95% confidence intervals (CI), the corresponding NNTs, control and experimental event rates, and the time-frame of the outcome assessment. RESULTS: We assembled a table of NNTs for 87 interventions in ten disease categories, deriving from meta-analyses (70%) or randomized controlled trials (30%), and assessing surgical interventions (7%), procedures (9%) or pharmacological treatments (84%). The NNTs varied widely, ranging from 1 in the use of epidural blood patch for post-dural puncture headache to 4608 for meningococcal vaccination. Preventative interventions had substantially larger NNTs. Time-frames were inappropriately short for many chronic conditions. CONCLUSIONS: Large collections of NNTs provide useful, updateable summaries of therapeutic effects in the neurosciences, an increasingly interventional clinical field.
Canada↗
Somatic comorbidity of epilepsy in the general population in Canada.
PURPOSE: There is a notion that people with epilepsy have substantial and often unrecognized comorbidity of chronic conditions. However, most studies focus on selected patient groups; population-based studies are scarce. We compared the prevalence of chronic somatic conditions in people with epilepsy with that in the general population using Canadian, nationwide, population-based health data. METHOD: We examined epilepsy-specific and general population health data obtained through two previously validated, independently performed, door-to-door Canadian health surveys, the National Population Health Survey (NPHS, N = 49,000) and the Community Health Survey (CHS, N = 130882), which represent 98% of the Canadian population. The prevalence of epilepsy and 19 other chronic conditions was ascertained through direct inquiry from respondents about physician-diagnosed illnesses. Weighted prevalence, prevalence ratios (PR), and 95% confidence intervals were obtained for the entire population and for males and females separately. Multivariate analyses assessed the strength of association of comorbid conditions with epilepsy as compared with the general population. RESULTS: People with epilepsy had a statistically significant higher prevalence of most chronic conditions than the general population. Conditions with particularly high prevalence in epilepsy (prevalence ratio > or = 2.0) include stomach/intestinal ulcers (PR, CHS 2.5, NPHS 2.7), stroke (PR, CHS 3.9, NPHS 4.7), urinary incontinence (PR, CHS 3.2, NPHS 4.4), bowel disorders (PR, CHS 2.0, NPHS 3.3), migraine (PR, CHS 2.0, NPHS 2.6), Alzheimer's disease (PR, NPHS 4.3), and chronic fatigue (PR, CHS 4.1). There were no gender-specific differences in prevalence of chronic conditions among people with epilepsy. CONCLUSIONS: People with epilepsy in the general population, not only those actively seeking medical care, have a high prevalence of chronic somatic comorbid conditions. The findings are consistent across two independent surveys, which show that people with epilepsy in the general population have a two- to five-fold risk of somatic comorbid conditions, as compared with people without epilepsy. This patient-centered comorbidity profile reflects health aspects that are important to people with epilepsy, and indicate the need for a more integrated approach to people with epilepsy. The impact of epilepsy relative to other comorbid conditions requires further analysis, as does the contribution of comorbidity to epilepsy intractability and to differential health care needs. Similarly, it remains to be determined whether the observed comorbidity patterns are specific to epilepsy or simply reflect a pattern that is common to chronic illnesses in general.
Adolescent↗
Prediction of aspiration in myasthenia gravis.
Prediction of the risk of dysphagia and aspiration is important in the management of myasthenia gravis (MG). We assessed the ability of four bedside clinical tools to predict aspiration in 20 MG patients. Patients completed a self-directed questionnaire, underwent clinical neurological assessment and a bedside speech pathology assessment, and were assessed with the quantitative myasthenia gravis (QMG) score. The ability of these tools to predict aspiration was compared with the results of a modified barium swallow. Seven patients aspirated, 4 silently. The total self-directed questionnaire score, two specific questions on the self-directed questionnaire, the prediction based on clinical neurological assessment, and the QMG bulbar subset score all correlated with aspiration. The speech pathology prediction was highly sensitive but less specific. This pilot study shows that simple clinical tools can predict which MG patients are at risk of aspiration.
Deglutition Disorders↗
Early epilepsy surgery.
Uncontrolled epilepsy is associated with progressive cortical and hippocampal atrophy, substantial cognitive and psychosocial morbidity, and increased mortality. Seizure freedom is required to reverse such morbidity and mortality. Surgery is vastly superior to medical therapy for patients with chronic, refractory temporal lobe seizures, and is now the standard of care for these patients. On the other hand, the concept of early surgery requires further exploration and definition. Although there is no robust, direct evidence to support early epilepsy surgery, case series and cohort studies report an association between earlier surgery and better outcomes. The evidence for earlier epilepsy surgery is reviewed.
Anticonvulsants↗
Spared somatomotor and cognitive functions in a patient with a large porencephalic cyst revealed by fMRI.
To date functional magnetic resonance imaging (fMRI) has not been extensively used in presurgical evaluation of patients with intractable epilepsy. Patient S.P. presented with left frontal originating seizures, secondary to a large porencephalic cyst that encompassed much of his occipital and temporal cortex and a substantial portion of ipsilateral parietal cortex. Nevertheless, S.P. did not demonstrate any gross impairments of praxis or speech. Scalp electroencephalogram (EEG) telemetry revealed reduced background activity in the left hemisphere, an absence of identifiable normal sleep states, and confirmed the left frontal origin of his seizures with a prolonged postictal state, suggesting that the remaining cortex in S.P.'s left hemisphere did not function normally despite his apparently normal appearance. Dichotic listening results also suggested that S.P. had an atypical language representation suggestive of either bilateral or right hemisphere speech representation. Surgical intervention to remove the remaining left hemisphere cortex was a serious consideration for treatment of S.P.'s seizures. We used fMRI to evaluate whether or not the remaining cortex in S.P.'s left hemisphere supported any cognitive or motor functions. Even though the volume of cerebral cortex was severely reduced and displaced in the left hemisphere, fMRI revealed significant activation in this remaining tissue in response to motor, somatosensory, and word generation tasks. In other words, we were able to demonstrate using fMRI that the remaining tissue in S.P.'s left hemisphere continued to support some motor and cognitive functions. The possible implications of these findings in terms of functional reorganisation are discussed briefly.
Brain Diseases↗
Effectiveness and safety of epilepsy surgery: what is the evidence?
Evidence from a recent randomized controlled trial of surgical versus medical therapy of temporal lobe epilepsy proves that antero-mesial resection is safe and more effective than medical therapy. The number of patients needed to treat for one patient to become free of disabling seizures is two, which is superior to most interventions in neurology. A meta-analysis of non-randomized trials gives almost identical results; about two-thirds of patients become seizure-free, compared with only 8% with medical therapy. The results are remarkably similar among studies from different parts of the world. Quality of life improves early after epilepsy surgery, the improvements are both statistically and clinically significant, and they are sustained. Surgical morbidity with clinically important permanent sequelae is 2%. Epilepsy surgery remains underutilized in developed countries and it does not exist in all but a few developing countries. Current randomized trials are underway to explore the effect of early surgery versus optimum medical therapy on the prevention of disability in patients with mesial temporal lobe epilepsy, and to examine the effectiveness of novel interventions, such as minimally invasive surgery and brain stimulation.
Anterior Temporal Lobectomy↗
National and regional prevalence of self-reported epilepsy in Canada.
PURPOSE: To assess the point prevalence of self-described epilepsy in the general population nationally, provincially, and in different groups of interest. METHODS: We analyzed data from two national health surveys, the National Population Health Survey (NPHS, N=49,000) and the Community Health Survey (CHS, N=130,882). Both surveys captured sociodemographic information, as well as age, sex, education, ethnicity, household income, and labor force status of participants. Epilepsy was ascertained with only one question in both surveys. "Do you have epilepsy diagnosed by a health professional?" (NPHS) and "Do you have epilepsy?" (CHS). Prevalences were age-adjusted by using national standard populations at the time of each survey. Exact 95% confidence intervals were obtained. RESULTS: In the NPHS, 241 of 49,026 subjects described themselves as having been diagnosed with epilepsy, yielding a weighted point prevalence of 5.2 per 1,000 [95% confidence interval (CI), 4.9-5.4]. In the CHS, 835 of 130,822 subjects described themselves as having epilepsy, yielding a weighted point prevalence of 5.6 per 1,000 (95% CI, 5.1-6.0). Trends in differences in prevalence among some Canadian provinces were observed. Prevalence was statistically significantly higher in groups with the lowest educational level, lowest income, and in those unemployed in the previous year. Prevalence also was higher in nonimmigrants than in immigrants. CONCLUSIONS: The overall and group-specific results are in keeping with those obtained in other developed countries by using different ascertainment methods. We discuss methodologic aspects related to the ascertainment of epilepsy in both surveys, and to the validity and implications of our findings.
Adolescent↗
Brain surgery for epilepsy.
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Adolescent↗
Comparative responsiveness of generic and specific quality-of-life instruments.
We assessed the relative responsiveness of generic and specific quality of life instruments in 43 randomized controlled trials that compared head-to-head 31 generic and 84 specific instruments. Using weighted effect size as the metric of responsiveness, we assessed the impact of instrument type, disease category, and magnitude of underlying therapeutic effect on responsiveness, and assessed the responsiveness of specific instruments relative to the corresponding domains of generic measures. In studies with a nonzero therapeutic effect, specific instruments (mean = 0.57) were significantly more responsive than generic instruments (mean = 0.39, P =.01), and than the corresponding domains of generic instruments (mean = 0.40, P =.03). Studies with low, medium, and high therapeutic effects showed a corresponding gradation in responsiveness differences between specific and generic instruments. We conclude that, overall, specific instruments are more responsive than generic tools, and that investigators may come to misleading conclusions about relative instrument responsiveness if they include studies in which the magnitude of the underlying therapeutic effect is zero.
Health Status Indicators↗
Dexamethasone for morbidity after subdural electrode insertion--a randomized controlled trial.
BACKGROUND: Invasive monitoring with subdural electrodes (SDE) for investigation of medically intractable epilepsy may be associated with undesirable immediate postoperative morbidity such as headache, nausea, vomiting, fever, and meningism. We undertook to evaluate the potential beneficial role of perioperative dexamethasone in reducing these symptoms. METHODS: In a double-blind placebo controlled clinical trial 30 patients undergoing SDE insertion were randomized to receive either placebo or a course of dexamethasone beginning one hour prior to surgery and tapering to discontinue over 72 hours postoperatively. Pain, pain relief, nausea, nausea relief, temperature, and meningism were assessed regularly in the postoperative period, and analgesic, antipyretic, and antiemetic drug requirements were tabulated. RESULTS: One patient was withdrawn from the dexamethasone group due to lack of data. With regards to postoperative pain, the direction of benefit favoured dexamethasone but a significant treatment by time interaction prevented further analysis of treatment effect. The dexamethasone group did have significantly lower temperatures and higher nausea relief scores. There was no statistically significant difference between the groups with regards to pain relief, nausea, and meningism scores. The beneficial effects of dexamethasone were delayed in onset, of limited duration, and not uniform over the observation period. CONCLUSION: Dexamethasone appears to have a role in reducing immediate morbidity following SDE insertion but its effect is not uniform in the postoperative period; it appears to be delayed in onset, and of limited duration. Further study is necessary to determine the ideal dosing schedule.
Adult↗
Practice parameter: temporal lobe and localized neocortical resections for epilepsy.
PURPOSE: To examine evidence for effectiveness of anteromesial temporal lobe and localized neocortical resections for disabling complex partial seizures. METHODS: Systemic review and analysis of the literature since 1990. RESULTS: One intention-to-treat Class I randomized controlled trial of surgery for mesial temporal lobe epilepsy found that 58% of patients randomized to be evaluated for surgical therapy (64% of those who received surgery) were free of disabling seizures and 10 to 15% were unimproved at the end of 1 year, compared with 8% free of disabling seizures in the group randomized to continued medical therapy. There was a significant improvement in quantitative quality-of-life scores and a trend toward better social function at the end of 1 year for patients in the surgical group, no surgical mortality, and infrequent morbidity. Twenty-four Class IV series of temporal lobe resections yielded essentially identical results. There are similar Class IV results for localized neocortical resections; no Class I or II studies are available. CONCLUSIONS: A single Class I study and 24 Class IV studies indicate that the benefits of anteromesial temporal lobe resection for disabling complex partial seizures is greater than continued treatment with antiepileptic drugs, and the risks are at least comparable. For patients who are compromised by such seizures, referral to an epilepsy surgery center should be strongly considered. Further studies are needed to determine if neocortical seizures benefit from surgery, and whether early surgical intervention should be the treatment of choice for certain surgically remediable epileptic syndromes.
Anticonvulsants↗