Acquisition of sensorimotor fMRI under general anaesthesia: Assessment of feasibility, the BOLD response and clinical utility.

We evaluated whether task-related fMRI (functional magnetic resonance imaging) BOLD (blood oxygenation level dependent) activation could be acquired under conventional anaesthesia at a depth enabling neurosurgery in five patients with supratentorial gliomas. Within a 1.5 T MRI operating room immediately prior to neurosurgery, a passive finger flexion sensorimotor paradigm was performed on each hand with the patients awake, and then immediately after the induction and maintenance of combined sevoflurane and propofol general anaesthesia. The depth of surgical anaesthesia was measured and confirmed with an EEG-derived technique, the Bispectral Index (BIS). The magnitude of the task-related BOLD response and BOLD sensitivity under anaesthesia were determined. The fMRI data were assessed by three fMRI expert observers who rated each activation map for somatotopy and usefulness for radiological neurosurgical guidance. The mean magnitudes of the task-related BOLD response under a BIS measured depth of surgical general anaesthesia were 25% (tumour affected hemisphere) and 22% (tumour free hemisphere) of the respective awake values. BOLD sensitivity under anaesthesia ranged from 7% to 83% compared to the awake state. Despite these reductions, somatotopic BOLD activation was observed in the sensorimotor cortex in all ten data acquisitions surpassing statistical thresholds of at least p < 0.001uncorr. All ten fMRI activation datasets were scored to be useful for radiological neurosurgical guidance. Passive task-related sensorimotor fMRI acquired in neurosurgical patients under multi-pharmacological general anaesthesia is reproducible and yields clinically useful activation maps. These results demonstrate the feasibility of the technique and its potential value if applied intra-operatively. Additionally these methods may enable fMRI investigations in patients unable to perform or lie still for awake paradigms, such as young children, claustrophobic patients and those with movement disorders.

Cerebrospinal fluid ferritin level, a sensitive diagnostic test in late-presenting subarachnoid hemorrhage.

The workup of patients with suspected subarachnoid hemorrhage (SAH) presenting late is complicated by a loss of diagnostic sensitivity of computed tomography (CT) brain imaging and cerebrospinal fluid (CSF) bilirubin levels. In this prospective longitudinal study of CSF ferritin levels in SAH, serial CSF samples from 14 patients with aneurysmal SAH requiring extraventricular drainage (EVD) were collected. The control group comprised 44 patients presenting with headache suspicious of SAH. Nine patients underwent a traumatic spinal tap. CSF ferritin levels were significantly higher in the patients with SAH compared with controls (P < .0001). The upper reference range of CSF ferritin is 12 ng/mL, and there was no significant difference between the traumatic and normal spinal taps (mean, 9.0 ng/mL vs 3.9 ng/mL; P = .59). CSF ferritin levels increased after SAH, from an average of 65 ng/mL on day 1 to 1750 ng/mL on day 11 (P < .01). Both the Fisher and Columbia CT scores were significantly correlated with CSF ferritin level. The increase in CSF ferritin level after SAH and possibly may provide additional diagnostic information in patients with suspected SAH who present late to the clinic.

Outcome in poor grade subarachnoid hemorrhage patients treated with acute endovascular coiling of aneurysms and aggressive intensive care.

BACKGROUND: Patients with poor grade (World Federation of Neurosurgeons (WFNS) Grades 4 and 5) subarachnoid hemorrhage (SAH) were historically considered to have a poor neurological outcome and therefore not traditionally offered aggressive treatment. In recent years there has been increasing evidence that early aggressive treatment of this patient group can result in a good outcome. Aim of this study is to identify the outcome of patients with WFNS Grade-4 and -5 SAH treated acutely with endovascular detachable coil embolization (DCE) and aggressive neurocritical care within our institution. METHODS: We retrospectively reviewed the records of patients with SAH WFNS Grades 4 and 5 treated with DCE within 7 days of admission between 1st January 2004 and 1st January 2008. Data collected included age, sex, grade SAH, position/number of Aneurysms, coiling complications, time spent on the neurosurgical critical care unit (NCCU), and 6-month outcome assessed by Glasgow outcome scale (GOS). GOS was dichotomized into good outcome (good recovery/moderate disability) and poor outcome (severe disability, vegetative, dead). RESULTS: A total of 193 acute SAH patients were admitted and treated within this time period, of these, 47 patients were classified as poor grade and included: 70% were female and 30% were male. The mean age was 56 years (33-88 years range). A total of 56 aneurysms were noted at angiography, 52 aneurysms were coiled. Complications of SAH Vasospasm was noted in 18 patients (38%), cerebral infarction in 13 patients (28%), seizures in 7 patients (15%), hydrocephalus in 25 patients (53%). Complications of DCE occurred in 2 patients (4% of total) these were an aneurysmal rupture and a peri-procedure thrombosis. Incomplete coiling occurred in another 5 patients (10.6% of total) due to technical difficulties. The median length of stay on the NCCU was 12 days (1-52 days range). Of the 47 poor grade patients coiled, 25 (53%) had a good outcome (good recovery/moderate disability) and 22 (47%) had a poor outcome (severe disability, vegetative, dead) by the time of the 6-month follow-up. CONCLUSION: Potentially, more than half the patients with WFNS Grade-4 and -5 SAH who are treated aggressively with coil embolization in association with supportive neurocritical care can achieve a good quality neurological outcome. However, it should be anticipated that these patients will spend a significant period of time in neurocritical care.

Marathon related death due to brainstem herniation in rehydration-related hyponatraemia: a case report.

INTRODUCTION: Identifying marathon runners at risk of neurological deterioration at the end of the race (within a large cohort complaining of exhaustion, dehydration, nausea, headache, dizziness, etc.) is challenging. Here we report a case of rehydration-related hyponatraemia with ensuing brain herniation. CASE PRESENTATION: We report the death of runner in his 30's who collapsed in the recovery area following a marathon. Following rehydration he developed a respiratory arrest in the emergency room. He was found to be hyponatraemic (130 mM). A CT brain scan showed severe hydrocephalus and brain stem herniation. Despite emergency insertion of an extraventricular drain, he was tested for brainstem death the following morning. Funduscopy demonstrated an acute-on-chronic papilledema; CSF spectrophotometry did not reveal any trace of oxyhemoglobin or bilirubin, but ferritin levels were considerably raised (530 ng/mL, upper reference value 12 ng/mL), consistent with a previous bleed. Retrospectively it emerged that the patient had suffered from a thunderclap headache some months earlier. Subsequently he developed morning headaches and nausea. This suggests that he may have suffered from a subarachnoid haemorrhage complicated by secondary hydrocephalus. This would explain why in this case the relatively mild rehydration-related hyponatremia may have caused brain swelling sufficient for herniation. CONCLUSION: Given the frequency of hyponatraemia in marathon runners (serum Na <135 mM in about 13%), and the non-specific symptoms, we discuss how a simple screening test such as funduscopy may help to identify those who require urgent neuroimaging.

Efficient synthesis of an imidazole-substituted delta-amino acid by the integration of chiral technologies.

Two methods to produce (2S)-5-amino-2-(1-n-propyl-1H-imidazol-4-ylmethyl)-pentanoic acid were investigated. Diastereoisomeric salt resolution, using the quinidine salt, gave the desired intermediate in 98% ee and 33% yield. Asymmetric hydrogenation of various substrates gave high conversions, with up to 83% ee. Integration of these two approaches via asymmetric hydrogenation of a quinidine salt substrate followed by crystallization provided the desired intermediate in 94% ee and 76% yield.