Analysis of pooled data from two pivotal controlled trials on the efficacy of topiramate in the prevention of migraine

CONTEXT: A substantial proportion of the patient population with migraine headache should be considered for preventive treatment based on the frequency and disability associated with this disorder. Use of the anticonvulsant topiramate was previously examined in two large, double-blind, randomized, placebo-controlled clinical trials of a subset of patients who have 3 to 12 migraine episodes per month. OBJECTIVE: To better characterize the efficacy of topiramate for prevention of migraine, with or without aura, by pooling and analyzing data from the two large clinical trials. METHODS: The pooled intent-to-treat population included 937 patients receiving topiramate at one of three dosages (50 mg/d, 100 mg/d, 200 mg/d) or placebo. Outcome measures included change in mean monthly migraine frequency and categorical responder rate throughout the 26-week doubleblind phase. Results: At daily doses of 100 and 200 mg, topiramate was associated with significant reductions in mean monthly migraine frequency throughout the double-blind phase compared with placebo (P<.001). Significantly more patients treated with these topiramate doses exhibited high-percentage reductions in monthly migraine frequency (>/=50% [P<.001], >/=75% [P<.001], 100% [P=.049]) versus placebo. The most common adverse events included anorexia, cognitive deficits, diarrhea, fatigue, nausea, and paresthesia. Topiramate (100 mg/d, 200 mg/d) was associated with significant and sustained reductions in mean monthly migraine frequency beginning as early as 1 week into therapy. CONCLUSION: Pooled efficacy data from two large, similarly designed, placebo-controlled migraine-prevention trials demonstrated that a statistically significant proportion of patients using topiramate met or exceeded two main outcome guidelines recommended by the International Headache Society (>/=50% and >/=75% reduction in frequency of monthly attacks). Based on efficacy and tolerability, topiramate at a dosage of 100 mg per day (50 mg twice daily) should be the target dosage for most patients with migraine.     

Visual imagery in cerebral visual dysfunction

Many sorts of deficits in imagery follow brain damage, but the relation between the site of damage and the type of deficit is not simple or straightforward. The dissociations in performance after brain damage provide hints regarding the processing system underlying imagery, but difficulties in interpretation urge caution in mapping these findings to theoretic models. Neuroimaging techniques, such as PET and fMRI, open a window into the working brain and offer valuable information not easily accessible through the study of patients, who, as noted, may have deficits beyond those observable and may rely on compensation and neural reorganization. As we come to understand the mental imagery system more fully, such issues as the laterality of image generation are likely to prove too coarse and vague. The brain is an enormously intricate organ, and even within a circumscribed domain such as imagery it seems to process information in complex and subtle ways.     

Comparative case series of exostoses and osteomas of the internal auditory canal

Exostoses and osteomas are benign bony lesions of the auditory canal. Although common in the external auditory canal, they are rare and difficult to distinguish in the internal auditory canal (IAC). In this literature review and case presentation, we define radiologic and histologic criteria to differentiate exostoses from osteomas of the IAC. Two patients with exostoses and 1 patient with an osteoma of the IAC are described here. Patient 1 presented with disabling vertigo and was found to have bilateral exostoses with nerve impingement on the right. After removal of the right-sided exostoses via retrosigmoid craniotomy, the patient had complete resolution of her symptoms over 1 year. Patient 2 presented with bilateral pulsatile tinnitus and vertigo and was found to have bilateral IAC exostoses. Patient 3 presented with hearing loss and tinnitus, and a unilateral IAC osteoma was ultimately discovered. Because of the mild nature of their symptoms, patients 2 and 3 were managed without surgery. We show that IAC osteomas can be differentiated from exostoses by radiographic evidence of bone marrow in high-resolution computed tomography scans, or by the presence of fibrovascular channels on histologic analysis. Management of these rare entities is customized on the basis of patient symptoms.     

Reduced implicit and explicit sequence learning in first-episode schizophrenia

A high prevalence of deficits in explicit learning has been reported for schizophrenic patients, but it is less clear whether these patients are impaired in implicit learning. Deficits in implicit learning indicative of a fronto-striatal dysfunction have been reported using a serial reaction-time task (SRT), but the impact of typical neuroleptic medication and chronicity remains controversial. The present study compared 37 patients with first-episode schizophrenia treated with atypical neuroleptics and 37 healthy matched control participants on two sequence learning tasks: a modified SRT for implicit sequence learning and a serial generation task (SGT) for explicit sequence learning. The two tasks were designed to be procedurally equivalent, in order to provide better comparability between implicit and explicit performance. Although unaffected in global cognitive functioning, schizophrenic patients were significantly impaired in implicit and explicit sequence learning. Deficient sequence learning in schizophrenic patients was neither related to psychopathology nor to chlorpromazine equivalent daily dosage. As performance was impaired even though patients were exclusively treated with atypical neuroleptics, the present findings concur with converging evidence of a sequence learning deficit inherent in schizophrenia. This deficit would be consistent with a fronto-striatal dysfunction and might constitute a crucial factor for the acquisition of new information.     

Sustained activities and retrieval in a computational model of the perirhinal cortex

The perirhinal cortex is involved not only in object recognition and novelty detection but also in multimodal integration, reward association, and visual working memory. We propose a computational model that focuses on the role of the perirhinal cortex in working memory, particularly with respect to sustained activities and memory retrieval. This model describes how different partial informations are integrated into assemblies of neurons that represent the identity of an object. Through dopaminergic modulation, the resulting clusters can retrieve the global information with recurrent interactions between neurons. Dopamine leads to sustained activities after stimulus disappearance that form the basis of the involvement of the perirhinal cortex in visual working memory processes. The information carried by a cluster can also be retrieved by a partial thalamic or prefrontal stimulation. Thus, we suggest that areas involved in planning and memory coordination encode a pointer to access the detailed information encoded in the associative cortex such as the perirhinal cortex.     

Value of routine screening for bone demineralization in an urban population of patients with epilepsy

BACKGROUND: Reduced bone mineral density (BMD) is increasingly recognized in patients receiving antiepileptic drug therapy. The precise prevalence is not known due to variability across populations studied. We set out to characterize the prevalence of abnormal BMD in an urban population of patients with epilepsy with the intent to determine the value of routine BMD screening. METHODS: We performed a cross-sectional study of 130 consecutive patients seen thorough our Comprehensive Epilepsy Center. BMD was measured using dual X-ray absorptiometry and was reported as T-score and Z-score. Additional information collected for each patient included age, race, gender, current and prior AEDs, ambulatory state, menopausal state, concomitant medications potentially associated with reduced bone mineralization, and comorbid illness potentially associated with reduced bone mineralization. Associations between reduced bone mineralization and variables were tested for significance using Fisher's exact test, Student's t-test, and Wilcoxon rank sum test. RESULTS: The average age of the entire study population was 43.5 (+/-12.5) years. Fifty-five percent of patients had T-score less than or equal to -1, the WHO criterion for osteopenia in postmenopausal women. The prevalence of Z-scores less than -2.0 was 15%, which is more than sixfold greater than expected. The markers for decreased BMD included older age or menopause in women, longer duration of therapy, and a history of use of phenytoin or phenobarbital. Assisted ambulation was also associated with low BMD. CONCLUSION: Our results indicate that reduced bone mineralization is prevalent and a significant health concern in an urban population of patients with epilepsy. Because of the high prevalence of reduced bone mineralization reported in numerous studies including this study, routinely screening for reduced bone mineralization is warranted in patients receiving anticonvulsant therapy.     

Optimizing robotic renal surgery: the lateral camera port placement technique and current results

PURPOSE: The successful completion of robot-assisted renal surgery requires optimal port placement in order to minimize arm collisions due to the bulky nature of the robotic system. We describe a novel technique of port placement to maximize range of motion during robotic renal surgery that has been used successfully in over 50 procedures and report on our results. METHODS: Five primary ports are placed utilizing a 30 degrees lens facing upward. The camera is in the most laterally placed port between the anterior axillary line and the midclavicular line, 3 to 4 cm below the costal margin. Two 8-mm robotic ports are placed 10 to 11 cm away from the camera port, triangulated towards the kidney. Assistant ports, if desired, are located medially and placed supra- (12 mm) and infraumbilically (5 mm). RESULTS: This technique resulted in the camera arm residing in an upward position, moving in a completely separate plane from the working robotic arms. We had no incidents of arm-camera collision in this position. We have used this port placement technique successfully in over 50 cases performed entirely robotically. We have had no need to change port location, redock the robotic system, or add additional ports during a procedure. CONCLUSION: We report on a port placement technique for robotic renal surgery that optimizes motion of the robotic arms, while eliminating external collisions. Placement of the camera port laterally and robotic ports anteromedially results in considerable flexibility of robotic arm movement.