M. Christopher Wallace

The North American Symptomatic Carotid Endarterectomy Trial: Surgical Results in 1415 Patients

BACKGROUND AND PURPOSE This study reports the surgical results in those patients who underwent carotid endarterectomy in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). METHODS The rates of perioperative stroke and death at 30 days and the final assessment of stroke severity at 90 days were calculated. Regression modeling was used to identify variables that increased or decreased perioperative risk. Nonoutcome surgical complications were summarized. The durability of carotid endarterectomy was examined. RESULTS In 1415 patients there were 92 perioperative outcome events, for an overall rate of 6.5%. At 30 days the results were as follows: death, 1.1%; disabling stroke, 1.8%; and nondisabling stroke, 3.7%. At 90 days, because of improvement in the neurological status of patients judged to have been disabled at 30 days, the results were as follows: death, 1.1%; disabling stroke, 0.9%; and nondisabling stroke, 4.5%. Thirty events occurred intraoperatively; 62 were delayed. Most strokes resulted from thromboembolism. Five baseline variables were predictive of increased surgical risk: hemispheric versus retinal transient ischemic attack as the qualifying event, left-sided procedure, contralateral carotid occlusion, ipsilateral ischemic lesion on CT scan, and irregular or ulcerated ipsilateral plaque. History of coronary artery disease with prior cardiac procedure was associated with reduced risk. The risk of perioperative wound complications was 9.3%, and that of cranial nerve injuries was 8.6%; most were of mild severity. At 8 years, the risk of disabling ipsilateral stroke was 5.7%, and that of any ipsilateral stroke was 17.1%. CONCLUSIONS The overall rate of perioperative stroke and death was 6.5%, but the rate of permanently disabling stroke and death was only 2.0%. Other surgical complications were rarely clinically important. Carotid endarterectomy is a durable procedure.

Clinical Course of Cranial Dural Arteriovenous Fistulas With Long-Term Persistent Cortical Venous Reflux

Background and Purpose— The natural history of aggressive (Borden 2 and 3) cranial dural arteriovenous fistulas (DAVFs) is not well described. Reported annual mortality and hemorrhage rates vary widely and range up to 20% per year. A consecutive single-center cohort of 236 cases that presented with a cranial DAVF between June 1984 and May 2001 was reviewed for the consequences of long-term persistent cortical venous reflux (CVR). Methods— A group of 118 cranial DAVFs was selected for the presence of CVR. All patients were offered treatment aimed at the disconnection of the CVR. Patients who declined or had partial treatment with persistence of the CVR had long-term clinical and angiographic follow-up to study the disease course of this select group. Results— Treatment was instituted in 101 of the 118 patients (85.6%). Three patients were lost to follow-up. The remaining 14 nontreated patients (11.9%) and the partially treated patients (n=6) were assessed clinically and angiographically over time. The mean follow-up in this select group was 4.3 years (86.9 patient-years). During follow-up, 7 patients suffered an intracranial hemorrhage (35%). The incidence of nonhemorrhagic neurological deficit was 30%. Nine patients (45%) died: 6 patients expired after a hemorrhage, and 3 patients died of progressive neurological deterioration. Two patients demonstrated a spontaneous closure of the DAVF (10%). Conclusions— Persistence of the CVR in cranial DAVFs yields an annual mortality rate of 10.4%. Excluding events at presentation, in this series the annual risk for hemorrhage or nonhemorrhagic neurological deficit during follow-up was 8.1% and 6.9%, respectively, resulting in an annual event rate of 15.0%.

Multidisciplinary management of spinal dural arteriovenous fistulas: Clinical presentation and long-term follow-up in 49 patients

Background and Purpose— In the early 1980s, it was demonstrated that surgical intradural division of the shunting vein to the medullary venous plexus cures a spinal dural arteriovenous fistula (DAVF) at low morbidity. There is, however, growing literature to support endovascular therapy. Methods— The clinical features of 49 consecutive patients with a spinal DAVF treated at a single institution between 1986 and 2001 were studied (mean age, 63 years; range, 28 to 78 years; 80% male). When possible, embolization was offered as the initial treatment. Endovascular treatment was considered adequate only if the proximal shunting vein could be occluded with liquid adhesive embolics. Motor and bladder function was evaluated with Aminoff scores an average of 32.3 months after treatment. Results— All but 1 patient presented with myelopathy. At a mean of 2.3 years after symptom onset, 48 DAVFs were angiographically demonstrated. Since 1999, gadolinium-enhanced MR angiography was additionally performed in 7 patients to point out the level of the DAVF. Endovascular embolization could be attempted in 44 of the 48 DAVFs and resulted in a cure in 11 (25%). Thirty-five DAVFs were surgically cured; 2 patients refused surgery after failed embolization. Angiographic confirmation of the treatment result was available in 97.7% of the patients. No permanent complications of either embolization or surgery were noted. Motor and bladder function scores were significantly improved in 35 patients who had long-term follow-up (both P <0.005). Conclusions— Endovascular treatment with liquid adhesive material provided a result equal to surgery in 25% of patients, overall resulting in a significant amelioration in the neurological status of patients with a spinal DAVF.

C1-C2 posterior cervical fusion: long-term evaluation of results and efficacy.

Posterior wiring techniques are the most commonly used methods of achieving C1-C2 arthrodesis. Recently, transarticular screw fixation and interlaminar clamping have been advocated to achieve more secure fixation. A retrospective review of patients undergoing C1-C2 fusion for nonneoplastic disease was undertaken at the University of Toronto Hospital, with the aim of determining the long-term outcome of the selected procedures. Thirty-two patients underwent 36 procedures from 1986 to 1992, with a mean follow-up of 4.7 +/- 2.2 years (range, 2.0-8.0 yr). The most common disease processes were odontoid fracture (18 patients), transverse atlantal ligament injury (5 patients), os odontoideum (5 patients), and rheumatoid C1-C2 instability (3 patients). Thirty-one Gallie fusions, one Brooks-Jenkins fusion, two transarticular screw fusions, and two Halifax clamp applications were performed. Six (19%) of Gallie/Brooks-Jenkins fusions failed. These occurred with os odontoideum (three patients), Type II odontoid fracture (two patients), and transverse atlantal ligament injury (one patient). All transarticular screw and Halifax clamp procedures resulted in successful fusions. Two procedures (6%) resulted in new neurological deficit; both of these patients underwent posterior wiring for os odontoideum. This study suggests that Type II odontoid fractures may be successfully managed by a posterior wiring technique alone. Rheumatoid C1-C2 instability may be managed by posterior wiring supplemented with halo immobilization. Transarticular screw fixation has several potential advantages as a technique for C1-C2 arthrodesis and, in particular, may be appropriate for os odontoideum that had a high failure rate (75%) with conventional posterior wiring, even when this was supplemented with halo bracing.

Angioarchitectural Factors Present in Brain Arteriovenous Malformations Associated With Hemorrhagic Presentation

Background and Purpose— Associations between clinical presentation of brain arteriovenous malformations (AVMs) and their angioarchitecture have been described. This study aims to identify significant factors related to the initial hemorrhagic event through multivariate statistical methodology. Methods— The authors studied the initial clinical presentation of 390 consecutive patients with brain AVMs at the University of Toronto Vascular Malformation Study Group. Angiographic features present at that time, such as location, size, and blood supply, were recorded following a standard protocol and associated, through multivariate analysis techniques, with type of presentation. Results— Patients had hemorrhagic presentation in 146 cases (37.4%). Hemorrhage was the initial presentation in 59.5% of the deep-seated AVMs (odds ratio [OR]=3.26; 95% CI=1.15 to 9.2;P =0.03). A single draining vein was associated with bleeding at presentation in 57.6% AVMs (OR=1.78; 95% CI=1.12 to 2.82;P =0.01), and 72.8% of the patients with venous ectasia had bleeding as initial evidence (OR=3.9; 95% CI=1.63 to 9.28;P =0.002). Hemorrhage was the initial presentation in 47.6% (111/233) of AVMs <3 cm, 22.5% (32/142) in sizes between 3 and 6 cm, and 20% in malformations >6 cm (3/15), but these differences were not significant in multivariate analyses. Conclusions— For initial hemorrhagic presentation, a small number of draining veins, deep location, and the presence of venous ectasias were significant associated factors. In contrast with many previous reports, AVM size was not associated with hemorrhage at presentation in adjusted analyses.

Large and Deep Brain Arteriovenous Malformations Are Associated With Risk of Future Hemorrhage

Background and Purpose— The correlation between features present in brain arteriovenous malformations (AVMs) such as size, location, and angioarchitecture at presentation with subsequent risk of hemorrhage may be valuable in predicting the behavior of AVMs and therefore guiding management. Methods— We prospectively followed up 390 patients with brain AVMs at the University of Toronto Vascular Malformation Study Group. Location, size, angioarchitecture details, blood supply, and clinical presentation were recorded at baseline. Intracranial hemorrhages during follow-up were recorded. Significant factors from univariate analyses were used to construct a multivariate model relating the above features to the occurrence of hemorrhage. Results— Thirty-eight patients had bleeding caused by the AVM in a follow-up of 1205 patient-years (mean, 3.1 years per patient). In analyses adjusted for multiple AVM characteristics, large AVMs bled more frequently than small lesions (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.41 to 4.35;P <0.0001), and deep-seated AVMs had more bleeding in follow-up than those located at superficial sites (OR, 5.56; 95% CI, 2.63 to 12.5;P <0.0001). Conclusions— Deep-seated and large AVMs were significantly more prone to hemorrhage during prospective follow-up. The distinction between factors associated with hemorrhagic presentation and the natural history risk of hemorrhage will be emphasized.

C1-C2 Posterior Cervical Fusion

Posterior wiring techniques are the most commonly used methods of achieving C1-C2 arthrodesis. Recently, transarticular screw fixation and interlaminar clamping have been advocated to achieve more secure fixation. A retrospective review of patients undergoing C1-C2 fusion for nonneoplastic disease was undertaken at the University of Toronto Hospital, with the aim of determining the long-term outcome of the selected procedures. Thirty-two patients underwent 36 procedures from 1986 to 1992, with a mean follow-up of 4.7 +/- 2.2 years (range, 2.0-8.0 yr). The most common disease processes were odontoid fracture (18 patients), transverse atlantal ligament injury (5 patients), os odontoideum (5 patients), and rheumatoid C1-C2 instability (3 patients). Thirty-one Gallie fusions, one Brooks-Jenkins fusion, two transarticular screw fusions, and two Halifax clamp applications were performed. Six (19%) of Gallie/Brooks-Jenkins fusions failed. These occurred with os odontoideum (three patients), Type II odontoid fracture (two patients), and transverse atlantal ligament injury (one patient). All transarticular screw and Halifax clamp procedures resulted in successful fusions. Two procedures (6%) resulted in new neurological deficit; both of these patients underwent posterior wiring for os odontoideum. This study suggests that Type II odontoid fractures may be successfully managed by a posterior wiring technique alone. Rheumatoid C1-C2 instability may be managed by posterior wiring supplemented with halo immobilization. Transarticular screw fixation has several potential advantages as a technique for C1-C2 arthrodesis and, in particular, may be appropriate for os odontoideum that had a high failure rate (75%) with conventional posterior wiring, even when this was supplemented with halo bracing.

Management of patients with brain arteriovenous malformations

Arteriovenous malformations (AVMs) of the brain, which are probably genetically determined, are errors in the development of the vasculature that, together with the effects of blood flow, may lead to a focal arteriovenous shunt. Clinically, the adult patient may present with acute or chronic neurological symptoms-fixed or unstable-such as deficits, seizures or headache. Sometimes the lesion is an incidental finding. In about half of the patients, the revealing event is an intracranial haemorrhage. The prevalence of AVM in the western world is probably <0.01% and the detection rate is about one per 100,000 person-years. Most AVMs are revealed in patients 20-40 years of age. Therefore, the risk of developing neurological symptoms from an AVM, usually because of haemorrhage, increases with patient age. In the young adult population, AVMs are significant risk factors for hemorrhagic stroke. This risk increases with AVM volume and is higher in centrally located AVMs. Almost all patients with AVM are subjected to treatment, either by surgery, radiosurgery or embolisation, with the functional aim of reducing the risk of haemorrhage or to alleviate neurological symptoms with an acceptable treatment risk. Few neurocentres have physicians highly skilled in all treatment modalities. Therefore, the prescribed treatment may not be defined from an objective assessment of what is optimal for each individual patient, but rather from local expertise. In this context, more and better data about the natural history and the outcome of different treatments, as well as predictive models, would be valuable to help to optimise the management. Management strategies obviously differ according to local preferences, but results presented in the literature suggest the following strategy: (I) cortically located AVMs with a nidus volume <10 ml could be operated, with or without presurgical embolisation, unless there is a single feeder that can easily be catheterised and embolised for obliteration or other obvious target for embolisation, such as pseudoaneurysms or large fistulae; (II) centrally located AVMs with a nidus volume <10 ml should be treated by radiosurgery, unless suitable for embolisation as indicated above; (III) patients harbouring AVMs with a nidus volume >10 ml could benefit from targeted partial embolisation followed by radiosurgery or surgery, depending on the angioarchitecture; and (IV) AVMs >20 ml nidus volume usually have a high treatment risk with any treatment modality and are not obvious targets for treatment at all.

Transient Ischemia Differentially Increases Tyrosine Phosphorylation of NMDA Receptor Subunits 2A and 2B

Abstract: Activation of the N‐methyl‐d‐aspartate (NMDA) receptor has been implicated in the events leading to ischemia‐induced neuronal cell death. Recent studies have indicated that the properties of the NMDA receptor channel may be regulated by tyrosine phosphorylation. We have therefore examined the effects of transient cerebral ischemia on the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B in different regions of the rat brain. Transient (15 min) global ischemia was produced by the four‐vessel occlusion procedure. The tyrosine phosphorylation of NR2A and NR2B subunits was examined by immunoprecipitation with anti‐tyrosine phosphate antibodies followed by immunoblotting with antibodies specific for NR2A or NR2B, and by immunoprecipitation with subunit‐specific antibodies followed by immunoblotting with anti‐phosphotyrosine antibodies. Transient ischemia followed by reperfusion induced large (23–29‐fold relative to sham‐operated controls), rapid (within 15 min of reperfusion), and sustained (for at least 24 h) increases in the tyrosine phosphorylation of NR2A and smaller increases in that of NR2B in the hippocampus. Ischemia‐induced tyrosine phosphorylation of NR2 subunits in the hippocampus was higher than that of cortical and striatal NR2 subunits. The enhanced tyrosine phosphorylation of NR2A or NR2B may contribute to alterations in NMDA receptor function or in signaling pathways in the postischemic brain and may be related to pathogenic events leading to neuronal death.

Chronic regenerative changes in the spinal cord after cord compression injury in rats.

Long-term regenerative changes and pathological effects after acute compression injury of the spinal cord were studied in rats. Twenty adult female Wistar rats underwent cord injury by the extradural clip compression technique at T6-7. Following injury, extradural electrodes attached to receiver-stimulators that were implanted subcutaneously were placed proximal and distal to the injury site. The animals were maintained in cages with electromagnetic fields created by encircling antennae. The control animals were in a field adjusted to a frequency below the sensitive frequency range of the receiver-stimulators so that they received no spinal cord stimulation. After 15-20 weeks of continuous spinal cord stimulation, histological sections of the cords were assessed and scored blindly for pathological changes including magnitude and extent of cord injury, and cystic cavitation, and for regenerative changes including proliferation of axons, Schwann cells and ependymal cells, and formation of myelin. In all 20 animals, there was a complete absence of normal cord tissue at the injury site, and cystic cavitation was frequently present at the injury site and beyond. Extensive regenerative changes were seen in all animals including regeneration of axons, Schwann cells and ependymal cells, and formation of myelin. Statistical analysis did not show a significant difference between treatment and control groups.