Epidural cortical stimulation as adjunctive treatment for non-fluent aphasia: preliminary findings.

BACKGROUND AND PURPOSE: This study evaluated the safety and feasibility of targeted epidural cortical stimulation delivered concurrently with intensive speech-language therapy for treatment of chronic non-fluent aphasia. METHODS: Eight stroke survivors with non-fluent aphasia received intensive behavioural therapy for 3 h daily for 6 weeks using a combination of articulation drills, oral reading and conversational practice. Four of these participants (investigational participants) also underwent functional MRI guided surgical implantation of an epidural stimulation device which was activated only during therapy sessions. Behavioural data were collected before treatment, immediately after treatment and at 6 and 12 weeks following termination of therapy. Imaging data were collected before and after treatment. RESULTS: Investigational participants showed a mean Aphasia Quotient change of 8.0 points immediately post-therapy and at the 6 week follow-up, and 12.3 points at 12 weeks. The control group had changes of 4.6, 5.5 and 3.6 points, respectively. Similar changes were noted on subjective caregiver ratings. Functional imaging suggested increased consolidation of activity in interventional participants. CONCLUSIONS: Behavioural speech-language therapy improves non-fluent aphasia, independent of cortical stimulation. However, epidural stimulation of the ipsilesional premotor cortex may augment this effect, with the largest effects after completion of therapy. The neural mechanisms underlying these effects are manifested in the brain by decreases in the volume of activity globally and in particular regions. Although the number of participants enrolled in this trial precludes definitive conclusions, targeted epidural cortical stimulation appears safe and may be a feasible adjunctive treatment for non-fluent aphasia, particularly when the aphasia is more severe.

The accuracy and reliability of 3D CT/MRI co-registration in planning epilepsy surgery.

OBJECTIVE: To investigate the accuracy and reliability of 3D CT/MRI co-registration technique for the localization of implanted subdural electrodes in the routine epilepsy presurgical evaluation, in so doing assess its usefulness in planning the tailored resection of epileptic focus. METHODS: Four external anatomic fiducial makers were used for co-registration of volumetric pre-implant brain MRI and post-implant head CT using Curry 5.0 software in 19 epilepsy presurgical candidates. The location of subdural electrodes derived from the co-registration was compared to that obtained by intra-operative digital photographs by using gyral/sulcal patterns and cortical vasculature as anatomic markers. RESULTS: The mean localization error was 4.3+/-2.5 mm in all 19 patients. However, the mean localization error was 3.1+/- 1.3 mm in 13 patients with all four reliable fiducial markers; whereas the mean localization error was 6.8+/-2.4 mm in 6 patients with two or three reliable fiducial markers. CONCLUSION: Visualization of subdural electrode positions on a patient's cortex can be accurately performed in the routine clinical setting by 3D CT/MRI co-registration. However, the accuracy of co-registration is dependent upon having reliable surface fiducial markers. In practice, confirmation of location accuracy, such as with intra-operative digital photographs, is necessary for planning of tailored resective surgery. SIGNIFICANCE: The combination of 3D CT/MRI co-registration and intra-operative digital photography techniques provides a practical and effective algorithm for the localization and validation of implanted subdural electrodes.

Noninvasive identification of human central sulcus: a comparison of gyral morphology, functional MRI, dipole localization, and direct cortical mapping.

The locations of the human primary hand cortical somatosensory and motor areas were estimated using structural and functional MRI, scalp-recorded somatosensory-evoked potential dipole localization, expert judgments based on cortical anatomy, and direct cortical stimulation and recording studies. The within-subject reliability of localization (across 3 separate days) was studied for eight normal subjects. Intraoperative validation was obtained from five neurosurgical patients. The mean discrepancy between the different noninvasive functional imaging methods ranged from 6 to 26 mm. Quantitative comparison of the noninvasive methods with direct intraoperative stimulation and recording studies did not reveal a significant mean difference in accuracy. However, the expert judgments of the location of the sensory hand areas were significantly more variable (maximum error, 39 mm) than the dipole or functional MRI techniques. It is concluded that because expert judgments are less reliable for identifying the cortical hand area, consideration of the findings of noninvasive functional MRI and dipole localization studies is desirable for preoperative surgical planning.

Randomized, pilot study of intermittent pneumatic compression devices plus dalteparin versus intermittent pneumatic compression devices plus heparin for prevention of venous thromboembolism in patients undergoing craniotomy.

BACKGROUND: Unfractionated heparin and the low molecular weight heparin, dalteparin, are used for prophylaxis against venous thromboembolism in patients undergoing craniotomy. These drugs were compared in a randomized, prospective pilot study comparing intermittent pneumatic compression devices plus dalteparin to intermittent pneumatic compression devices plus heparin. METHODS: One hundred patients undergoing craniotomy were randomly allocated to receive perioperative prophylaxis with subcutaneous (SC heparin, 5000 units every 12 hours, or dalteparin, 2,500 units once a day, begun at induction of anesthesia and continued for 7 days or until the patient was ambulating. Entry criteria were age over 18 years, no deep vein thrombosis (DVT) preoperatively as judged by lower limb duplex ultrasound and no clinical evidence of pulmonary embolism preoperatively. Patients with hypersensitivity to heparin, penetrating head injury or who refused informed consent were excluded. Patients underwent a duplex study 1 week after surgery and 1 month clinical follow-up. All patients were treated with lower limb intermittent pneumatic compression devices. RESULTS: There were no differences between groups in age, gender, and risk factors for venous thromboembolism. There were no differences between groups in intraoperative blood loss, transfusion requirements or postoperative platelet counts. Two patients receiving dalteparin developed DVT (one symptomatic and one asymptomatic). No patient treated with heparin developed DVT and no patient in either group developed pulmonary embolism. There were two hemorrhages that did not require repeat craniotomy in patients receiving dalteparin and one that did require surgical evacuation in a patient treated with heparin. Drug was stopped in two patients treated with dalteparin because of thrombocytopenia. None of these differences were statistically significant. CONCLUSION: There was no significant difference in postoperative hemorrhage, venous thromboembolism or thrombocytopenia between heparin and dalteparin. The results suggest that, given the small sample size of this trial, both drugs appear to be safe and the incidence of venous thromboembolism by postoperative screening duplex ultrasound appears to be low when these agents are used in combination with intermittent pneumatic compression devices.

Transient inability to distinguish between faces: electrophysiologic studies.

It is not known with certainty at which level of face processing by the cortex the distinction between a familiar and an unfamiliar face is made. Subdural electrodes were implanted under the fusiform gyrus of the right temporal lobe in a patient who developed an unusual inability to distinguish differences between faces as part of the epileptic aura ("all faces looked the same"). A cortical region located posterior to the epileptic focus was identified that exhibited a maximum evoked response to the presentation of facial images (N165), but not to objects, scenes, or character strings. Evoked potentials elicited by a variety of visual images indicated that any perturbation away from novel whole-face stimuli produced submaximal responses from this region of the right temporal lobe. Electrical stimulation of this region resulted in an impairment of face discrimination. It was found that presentation of familiar faces (grandmother, treating physician) produced a different response from that observed for novel faces. These observations demonstrate that within 165 msec of face presentation, and before the conscious precept of face familiarity has formed, this cortical region has already begun to distinguish between a familiar and an unfamiliar face.

Clinical and molecular analysis of disseminated hemangioblastomatosis of the central nervous system in patients without von Hippel-Lindau disease. Report of four cases.

Hemangioblastomas of the central nervous system (CNS) may occur sporadically or in association with von Hippel-Lindau (VHL) syndrome. The authors present four patients with no family history or clinical evidence of VHL syndrome in whom extensive, progressive, en plaque coating of the brainstem and spinal cord with hemangioblastomas developed 1 to 8 years after complete resection of a solitary cerebellar hemangioblastoma. Analysis included detailed physical, biochemical, radiological, and pathological examinations in all four patients, combined with family pedigree analysis. In addition, a detailed investigation of the VHL gene was undertaken. Allelic loss, comparative genomic hybridization (CGH), single-stranded conformational polymorphism screening, CpG island methylation status, and X chromosome inactivation clonality analyses were performed. Although there was no evidence of germline alterations in the VHL gene on clinical and radiological examination or in the family history (all four patients) or analysis of peripheral blood (three patients), somatic deletion of one copy of the VHL gene occurred in these tumors. These findings indicate that the multiple, separate deposits of tumors were likely derived from a single clone. Results of CGH indicate that one or several additional genes are probably involved in the malignant behavior of the hemangioblastomas in these patients. Furthermore, the malignant biological and clinical behavior of these tumors, in which multiple sites of subarachnoid dissemination developed 1 to 8 years after initial complete resection, followed by progressive tumor growth and death of the patients, occurred despite a histological appearance typical of benign hemangioblastomas. Malignant hemangioblastomatosis developed 1 to 8 years after resection of an isolated cerebellar hemangioblastoma. Alterations of the VHL gene may be permissive in this setting, but other genes are likely to be the source of the novel biological and clinical presentation of the disseminated hemangioblastomas in these patients. This appears to represent a novel condition in which the product of one or more mutations in several genes permits malignant tumor behavior despite retention of a benign histological picture, a circumstance previously not recognized in CNS tumors.