Surgery for epilepsy: assessing evidence from observational studies.

The effectiveness of epilepsy surgery is mostly based on the results of observational studies because an experimental design in surgical patients has several ethical implications. However, observational studies suffer from methodological drawbacks, which prevent meaningful conclusions and represent a serious limitation when data from different reports are pooled for systematic reviews and meta-analyses. These include the retrospective design, the use of referral populations, the small sample size, the enrolment of patients at differing inception points, the use of differing inclusion criteria, differing definitions of prognostic predictors and outcome measures, the unmasked assessment of outcome, the short follow-up, the changing technologies and surgical procedures, and the inadequate statistical methods. With these limitations in mind, a systematic review was performed of epilepsy surgery studies aiming at identifying the positive and negative prognostic predictors of surgical outcome. In this review, extent of surgical resection, abnormal MRI, mesial temporal sclerosis, febrile seizures, EEG/MRI concordance, and tumor were in decreasing order the principal indicators of the success of surgery of epilepsy. By contrast, intracranial monitoring and post-operative discharges tended to predict an unfavorable prognosis. Although the heterogeneity of the study results was fairly low, the results may be affected by pooling of data from heterogeneous reports (different patient series assessed with differing methods) or unexamined or unknown confounders. These data must be considered preliminary and cannot replace well-conducted prognostic studies (representative study populations, well-defined inception cohorts, satisfactory and complete follow-up, prospective design, and standard definition of prognostic factors).

Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomised, pragmatic controlled trial.

OBJECTIVE: To evaluate the value of alternative monotherapy versus adjunctive therapy in partial epilepsy refractory to single antiepileptic drug (AED) therapy. DESIGN AND METHODS: In a multicentre, parallel-group, open-label study, patients with cryptogenic or symptomatic partial epilepsy not controlled after single or sequential AED monotherapies were randomised to monotherapy with an alternative AED or to adjunctive therapy with a second AED. The AED to be added/substituted and dose adjustments were determined by the physician's best judgement. Patients were followed up until withdrawal from the allocated treatment or for 12 months, whichever first. Outcome measures included proportion of patients continuing on the assigned treatment strategy, proportion of patients seizure-free after achieving the target maintenance dose, and adverse effects rates. Data were analysed by actuarial life tables, Kaplan-Meier survival analysis and Cox proportional hazard regression model. RESULTS: Of a total of 157 patients (including 94 previously exposed to only one AED), 76 were randomised to alternative monotherapy and 81 to adjunctive therapy. The two groups were balanced in clinical characteristics. The 12-month cumulative probability of remaining on the assigned treatment was 55% in patients randomised to alternative monotherapy and 65% in those randomised to adjunctive therapy (P=0.74). The 12-month probability of remaining seizure-free was 14 and 16%, respectively (P=0.74). Adverse effects were similar in the two groups. No significant differences in outcome within or between groups were identified based on etiology of epilepsy and previous AED exposure. CONCLUSIONS: Although these findings should be interpreted with caution due to the low statistical power resulting from the relatively small sample size, alternative monotherapy and adjunctive therapy were associated with similar outcomes. Further work is required to determine whether outcome could be improved through identification of specific AED combinations with synergistic activity.

Reliability of the El Escorial diagnostic criteria for amyotrophic lateral sclerosis.

BACKGROUND: The El Escorial diagnostic criteria are the most commonly used in clinical studies and therapeutic trials in patients with amyotrophic lateral sclerosis (ALS). The accuracy of the El Escorial criteria was tested in clinical practice, but the reliability is unknown when the diagnosis of ALS must be assessed on the basis of medical records. OBJECTIVE: To assess the reliability of the El Escorial criteria for the diagnosis of ALS in different settings. DESIGN AND METHODS: Semistructured forms were used to include the main diagnostic information on 20 patients with definite (n = 6), probable (n = 6), possible (n = 6), and suspected ALS (n = 2) and 19 patients with clinical conditions considered in the differential diagnosis. Agreement was tested by comparing the diagnosis made by the attending physician (the 'gold standard') with that of 4 raters with different backgrounds: a teaching neurologist with research and practical experience in the field of motor neuron disorders, a neurologist with specific interest in motor neuron disorders and neurophysiological background, a neurophysiologist, and a general neurologist with only occasional ALS patients. Sources of disagreement were discussed and the agreement was tested further on the medical records of 98 additional cases taken from an ongoing ALS registry. Eight additional cases (ALS: 4; other conditions: 4) were examined directly by the 4 raters. RESULTS: The interrater agreement on the medical records was poor (overall kappa 0.05-0.29). When the differential diagnosis was made between ALS (all diagnostic levels) and other conditions, interrater agreement was at best modest, with moderate variations when raters were compared in pairs (kappa 0.03-0.58) and when each rater was compared with the physician (kappa 0.27-0.51). Agreement was higher after direct examination of the patients (kappa 0.33-1) and increased significantly on the medical records after training (overall kappa 0.52-0.79). However, concordance was low (overall kappa 0.08-0.36), even after training, at the lowest diagnostic level (definite to suspected ALS vs. other conditions). CONCLUSIONS: The El Escorial criteria are a poor diagnostic indicator when patients' records are examined. Although medical education significantly improves the reliability of the criteria, concordance is still modest when the diagnosis includes suspected ALS.