Stuart Ross

A Review of Delayed Ischemic Neurologic Deficit Following Aneurysmal Subarachnoid Hemorrhage: Historical Overview, Current Treatment, and Pathophysiology

Delayed ischemic neurologic deficit (DIND) is a serious and poorly understood complication of aneurysmal subarachnoid hemorrhage. Although advances in treatment have improved prognosis for these patients, long-term clinical outcomes remain disappointing. Historically, angiographic vasospasm was thought to result in a DIND, although an increasing body of evidence suggests that this is an oversimplification, because interventions that have effectively targeted angiographic vasospasm have not improved outcome. Consequently, the relationship between angiographic vasospasm and neurologic outcome may be associative rather than causative. Although our understanding of the underlying molecular processes and pathophysiology is improving, responsible mediators or pathways have yet to be identified. The aim of this review is to summarize the key historical events that have helped shape our understanding of the pathophysiology of this phenomenon (microcirculation, autoregulation, microthrombosis, inflammation, apoptosis, spreading depolarization, oxidative stress) and to present the evidence underlying current treatment strategies (hemodynamic therapy, oral nimodipine, endovascular therapy, statins, cerebrospinal fluid drainage, thrombolysis, magnesium) and the translational and clinical research investigating DIND.

Lumbar Drainage of Cerebrospinal Fluid After Aneurysmal Subarachnoid Hemorrhage: A Prospective, Randomized, Controlled Trial (LUMAS)

Background and Purpose— A single-center prospective randomized controlled trial has been conducted to determine if lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage reduces the prevalence of delayed ischemic neurological deficit and improves clinical outcome. Methods— Patients with World Federation of Neurological Surgeons Grade 1 to 3 aneurysmal subarachnoid hemorrhage and modified Fisher Grades 2, 3, 4, and 3+4 were randomized to either the study group of standard therapy plus insertion of a lumbar drain or the control group of standard therapy alone. The primary outcome measure was the prevalence of delayed ischemic neurological deficit. Results— Two hundred ten patients with aneurysmal subarachnoid hemorrhage (166 female, 44 male; median age, 54 years; interquartile range, 45–62 years) were recruited into the control (n=105) and study (n=105) groups of the trial. World Federation of Neurological Surgeons grade was: 1 (n=139), 2 (n=60), and 3 (n=11); Fisher grade was: 2 (n=87), 3 (n=85), and 4 (n=38). The prevalence of delayed ischemic neurological deficit was 35.2% and 21.0% in the control and study groups, respectively (P=0.021). The prevalence of a modified Rankin Scale score of 4, 5, or 6 at Day 10 and 6 months, respectively, was 62.5% and 18.6% in the control group and 44.8% and 19.8% in the study group (P=0.009 and 0.83, respectively). Conclusions— Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage has been shown to reduce the prevalence of delayed ischemic neurological deficit and improve early clinical outcome but failed to improve outcome at 6 months after aneurysmal subarachnoid hemorrhage. Clinical Trial Registration— URL: www.clinicaltrials.gov. Unique identifier: NCT00842049.

Self-perceived health status following aneurysmal subarachnoid haemorrhage: a cohort study.

Objective The objective of the study was to assess the long-term self-reported health status and quality of life (QoL) of patients following an aneurysmal subarachnoid haemorrhage (ASAH) using a self-completed questionnaire booklet. Design A two-cohort study. Setting A regional tertiary neurosurgical centre. Participants 2 cohorts of patients with ASAH treated between 1998 and 2008 and followed up at approximately 1 year. Interventions Routine care. Primary and secondary outcomes A range of standardised scales included: AKC Short Sentences Test, the Barthel Index, the Self-Report Dysexecutive Questionnaire, the Everyday Memory Questionnaire, Stroke Symptom Checklist, Wimbledon Self-Report Scale, Modified Rankin Score (MRS) and a new Stroke-QoL. The data from summated scales were fit to the Rasch measurement model to validate the summed score. Results 214 patients (48%) returned the questionnaires; the majority (76%) had a World Federation of Neurosurgeons grade of 1 or 2. The most frequent aneurysm type was that of the anterior communicating artery (28%) with approximately 90% of aneurysms of the anterior circulation. Of those previously in full or part-time employment, 48.9% were unemployed at follow-up. All summated scales satisfied the Rasch measurement model requirements, such that their summed scores were a sufficient statistic. Given this, one-third of patients were noted to have a significant mood disorder and 25% had significant dysexecutive function. Patients with an MRS of 3, 4 or 5 had significantly worse scores on most outcome measures, but a significant minority of those with a score of zero had failed to return to work and displayed significant mood disorder. Conclusions A range of self-reported cognitive and physical deficits have been highlighted in a cohort of patients with ASAH. While the MRS has been shown to provide a reasonable indication of outcome, in routine clinical follow-up it requires supplementation by instruments assessing dysexecutive function, memory and mood.

Endovascular treatment of cerebral aneurysms using the Woven EndoBridge technique in a single center: preliminary results

OBJECTIVE The Woven EndoBridge (WEB) is an innovative new technique for securing cerebral aneurysms. It is designed particularly for wide-necked bifurcation aneurysms that otherwise would be difficult to treat. There is a paucity of follow-up data in the literature due to the novelty of this technique. The authors reviewed their data from cases involving patients treated at Leeds General Infirmary with the WEB device. They assessed the safety and complication risk associated with the device and clinical and radiological follow-up outcomes in their patients. This is, to their knowledge, the first publication to include the new single-layer sphere device (WEB SLS) in addition to the original dual-layer (WEB DL) and the (nonsphere) single-layer (WEB SL) devices. METHODS Data from 22 patients who underwent 25 WEB treatments were analyzed. Of the 25 WEB procedures, 3 were performed on an acute basis, 1 was performed on a semiacute basis, and the remaining 21 were elective. A novel 6-point scoring system called the Leeds WEB aneurysm occlusion scale was created to ensure accurate assessment based on the morphology of the WEB device. Outcome was assessed at follow-up by MR angiography with or without digital subtraction angiography and the modified Rankin Scale (mRS). RESULTS Deployment of the WEB device was successful in 22 (88%) of 25 procedures; 3 (12%) of the attempts at WEB treatment were abandoned. One of the patients in whom treatment was abandoned underwent a successful second attempt. Immediately after the 22 procedures with successful deployment, 4 (18%) of the patients had a complete occlusion of the aneurysm and WEB device; 10 (45%) had varying degrees of occlusion within the WEB device but no aneurysm neck or remnant; 3 (14%) had a neck remnant; and 5 (23%) had an aneurysm remnant. Of the patients with an aneurysm remnant, 1 had a complete aneurysm occlusion at ≥ 3-months follow-up. In total, 6 (27%) patients had a residual aneurysm at ≥ 3-months radiological follow-up. One of these patients was admitted with hydrocephalus secondary to a recurrent aneurysm and later received a second WEB treatment with additional coiling. Only 1 patient developed new neurological symptoms. This patient went from an mRS score of 0 to a score of 1 and had radiological evidence of a thromboembolic event. Two patients showed radiological evidence of a new thromboembolic event on follow-up MRI but were clinically asymptomatic. CONCLUSIONS The WEB has shown itself to be a promising new device with the potential to increase the scope of treatment for difficult wide-necked bifurcation aneurysms. The technique is safe, and short-term results show effective occlusion of complex aneurysms with minimal complications associated with the procedure. Long-term efficacy, however, still needs to be assessed.

A comparison of the outcome of aneurysmal subarachnoid haemorrhage before and after the introduction of an endovascular service

There has been a rapid change from predominantly surgical to endovascular treatment of ruptured intracranial aneurysms giving the opportunity to assess change in patient outcome during this transition. We identified and followed 139 patients with subarachnoid haemorrhage (SAH) treated in the year prior to (group 1) and following (group 2) the introduction of an endovascular service in a retrospective, cross-sectional study. A total of 78.7% of patients in group 1 underwent surgical treatment, 10.7% underwent endovascular treatment and 10.7% received no treatment, whereas patients in group 2 received 29.7%, 65.7% and 4.7%, respectively. MRS scores were obtained in 91% of patients in group 1 and in 89% of patients in group 2. A total of 30.7% and 24.0% of patients had a poor outcome in groups 1 and 2 respectively (p=0.34). The overall change in the management of ruptured cerebral aneurysms in the post-International Subarachnoid Aneurysm Trial (ISAT) era has not significantly changed cross-sectional outcome, although absolute differences appear to reflect difference in outcome noted in the ISAT.

New Modalities to Assess Efficacy of Triple-H Therapy: Early Experience

The traditional axiom that vasospasm induced reduction of blood flow leads to poor tissue oxygenation and ischaemic cellular injury culminating in delayed neurological deficits has been challenged and the efficacy of triple H therapy in reversal of the above is debated. In this study we assess cerebral physiology before and during onset of DIND and with application of triple H therapy with real time neuro-monitoring tools. Patients with Fisher grade 3/4/3 + 4/rebleed were consented. Probes for measuring rCBF, pTiO2, and Microdialysis parameters - glucose, glycerol, lactate, and pyruvate were inserted at time of coiling/clipping. Subsequent monitoring was done in HDU/ITU setting. Return of parameters to baseline was regarded as effective triple H therapy. Study is ongoing and the current paper presents our experience with first five patients. The results suggest safety and feasibility of multimodal monitoring in clinical setting to establish an understanding of relationship between clinical symptoms, brain perfusion, oxygenation, and metabolism in real time to test and guide therapy in future.

Kinematic measures provide useful information after intracranial aneurysm treatment

Introduction Current methods of assessing the outcomes of intracranial aneurysm treatment for aneurysmal subarachnoid haemorrhage are relatively insensitive, and thus unlikely to detect subtle deficits. Failures to identify cognitive and motor outcomes of intracranial aneurysm treatment might prevent delivery of optimal post-operative care. There are also concerns over risks associated with using intracranial aneurysm treatment as a preventative measure. Methods We explored whether our kinematic tool would yield useful information regarding motor/cognitive function in patients who underwent intracranial aneurysm treatment for aneurysmal subarachnoid haemorrhage or unruptured aneurysm. Computerised kinematic motor and learning tasks were administered alongside standardised clinical outcome measures of cognition and functional ability, in 10 patients, as a pilot trial. Tests at post-intracranial aneurysm treatment discharge and six-week follow-up were compared to see which measures detected changes. Results Kinematic tests captured significant improvements from discharge to six-week follow-up, indexed by reduced motor errors and improved learning. Increased Addenbrooke’s Cognitive Examination-Revised scores reflected some recovery of memory function for most individuals, but other standardised cognitive measures, functional outcome scores and a psychological questionnaire showed no changes. Conclusions Kinematic measures can identify variation in performance in individuals with only slightly improved abilities post-intracranial aneurysm treatment. These measures may provide a sensitive way to explore post-operative outcomes following intracranial aneurysm treatment, or other similar surgical procedures.

Identifying patient report outcomes relevant to aneurysmal subarachnoid hemorrhage follow-up.

Patients recovered from subarachnoid hemorrhage can be assessed for neuropsychological dysfunction using postal questionnaires. We assessed 214 patients using various tests of memory, mood and strategic thinking. Patients in good outcome categories (modified Rankin Scale [mRS] 0-1) nevertheless exhibited mood disorder (28%), memory deficit and executive dysfunction (20%). Return to work (49%) was most influenced by previous employment status, Rankin scale and mood.

Evidenced Based Guidelines for the Management of Good Grade Subarachnoid Haemorrhage Patients in Leeds, UK

Aneurysmal Subarachnoid Haemorrhage (SAH) is a common neurosurgical condition with high morbidity and mortality, with our trust treating over 120 patients annually. Although there are recommendations for the management of some aspects of subarachnoid haemorrhage, a comprehensive guideline document has not been produced. Our guidelines seek to address all aspects of acute patient care in our neurosurgical unit, using evidence based medicine with a multi-disciplinary team to produce care pathways establishing a standard of care for our patients.

High grade glioma in a focal cortical dysplastic lesion.

A 61-year-old woman presented in 1999 with a recent onset of left-sided focal clonic seizures with associated vague speech arrests. A computerised tomography (CT) scan revealed a hypoattenuated non-enhancing lesion within her right temporal lobe which was biopsied and the histopathological features were reported to be consistent with a hamartoma, reminiscent of tuberous sclerosis. Her seizures remained partially controlled with phenytoin and carbamazepine. She presented again 2 years later with an increase in the frequency of her seizures. A magnetic resonance scan of her brain demonstrated a homogenously enhancing mass lesion in her right temporo-parietal lobe. An initial lobectomy showed a hamartomatous lesion on histology but a subsequent sample obtained from a wide resection carried out when there was further worsening of her condition revealed a grade IV astrocytoma within a focal cortical dysplastic lesion. Our case highlights the importance of considering the possibility of a cortical dysplastic lesion harbouring a malignancy and the need for further research to explore the behaviour of these malformative lesions.