Michael Bynevelt

Systemic markers of inflammation are independently associated with S100B concentration: results of an observational study in subjects with acute ischaemic stroke

BackgroundVascular dysfunction and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke. However acute inflammation and vascular dysfunction may simply be markers of an acute phase response to cerebral injury, reflecting the size of the cerebral lesion. We aimed to determine if systemic markers of vascular dysfunction and inflammation are independently associated with concentrations of the astroglial protein S100B, a marker of brain injury, in participants with acute ischaemic stroke.MethodsFifty-seven men and women recruited within 96 hours of acute ischaemic stroke at two tertiary hospitals participated in this cross sectional observational study. Clinical, imaging (stroke lesions area measured with perfusion CT) and laboratory data were the independent variables and co-variates. The outcome variable was serum S100B concentration, analysed by multivariate regression.ResultsHigh sensitivity-CRP (B = 0.41) and lesion area (B = 0.69) were independently associated with S100B concentration (R2 = 0.75, p < 0.01). Other variables with significant univariate associations with S100B concentration were not independently associated with S100B concentration in the final multivariate model.ConclusionThe degree of systemic inflammation is associated with S100B concentration in acute ischaemic stroke, independent of the size of the ischaemic lesion.

Magnetic resonance imaging of the subthalamic nucleus for deep brain stimulation

The subthalamic nucleus (STN) is one of the most important stereotactic targets in neurosurgery, and its accurate imaging is crucial. With improving MRI sequences there is impetus for direct targeting of the STN. High-quality, distortion-free images are paramount. Image reconstruction techniques appear to show the greatest promise in balancing the issue of geometrical distortion and STN edge detection. Existing spin echo- and susceptibility-based MRI sequences are compared with new image reconstruction methods. Quantitative susceptibility mapping is the most promising technique for stereotactic imaging of the STN.

DuraSeal-hematoma: concealed hematoma causing spinal cord compression.

Study Design. Case description. Objective. To present a case report which highlights a complication following the use of Duraseal in posterior cervical surgery. Summary of Background Data. Duraseal is increasingly used to repair cranial and spinal dural defects to prevent cerebrospinal fluid leakage. Although it is well established that the hydrogel expands after implantation and may result in compressive effects, the phenomenon of Duraseal-entrapped hematoma has not previously been reported. Methods. The authors report a 80-year-old woman who presented with cervical myelopathy secondary to canal stenosis. The patient underwent decompressive cervical laminectomies. The surgery was complicated by an unintended durotomy. A thin layer of Duraseal was applied over the dural surface and a suction drain placed before wound closure. The patient awoke from surgery without any new neurologic deficits but experienced delayed functional deterioration. Urgent magnetic resonance imaging demonstrated an extradural hematoma with severe cord compression. Results. The patient underwent urgent surgery. Intraoperatively, the Duraseal was found to have formed a restrictive layer, completely entrapping the extradural hematoma with resultant spinal cord compression. Minimal blood clot was found external to the hydrogel layer. Conclusion. Although Duraseal can provide an effective and water-tight dural repair, it also has the potential to “entrap” extradural bleeding which otherwise may have been evacuated by a wound drain placed under suction. Our experience has shown that Duraseal should be used judiciously with recognition of this potential complication.

A randomized placebo controlled trial of early treatment of acute ischemic stroke with atorvastatin and irbesartan

Background Cholesterol and blood pressure lowering therapies are effective in the secondary prevention of ischemic stroke. Aim To determine whether 30 days of treatment with atorvastatin, or irbesartan, initiated within 96 h of symptom onset improves recovery from acute ischemic stroke. Methods Eighty-one patients with acute ischemic stroke participated in this double-blind, placebo-controlled, randomized trial of atorvastatin (80 mg) vs. placebo, and/or irbesartan (150 mg) vs. placebo. Fifty-two patients (randomized 53 ± 22 h after onset of symptoms) completed the 30-day primary outcome follow-up. Results The primary outcome, maximal brain infarct size at days 3 and 30 measured by perfusion computed tomography, was not significantly altered by random assignment to irbesartan (1088 (IQR 216, 2594) mm2 at day 3, compared with 398 (144, 2053) mm2 among the placebo group, P=0·79 controlling for baseline values; and 822 (159, 1717) mm2 at day 30, cf 280 (76, 1330) mm2; P=0·63); or atorvastatin (454 (107, 1765) mm2 cf 825 (265, 2509) mm2 at day 3; P=0·33; and 462 (43, 1399) mm2 cf 280 (128, 1559) mm2 at day 30, P=0·79). There were no other significant differences among the treatment groups with the exception of: • high sensitivity C-reactive protein concentrations, which were lower in the irbesartan treatment group at day 30 (mean difference 12·6 mg/L; 95% CI: −25·1, −0·1; P=0·048); and • the mean cerebral blood flow in the affected cerebral hemisphere at 30 days after stroke, which was significantly reduced by random assignment to irbesartan compared with placebo in both the affected cerebral hemisphere (−7·5 mL/100 mL/min (95% CI: −1·7 to −13·4, P=0·01)) and in the unaffected hemisphere (−7·3 mL/100 mL/min (95% CI: −1·3, −13·4; P=0·02)). Atorvastatin therapy was well tolerated, but irbesartan therapy was associated with an increased rate of withdrawal from therapy (n=10 (29%), compared with n=3 (9%) who withdrew from placebo, P=0·04). Conclusions Treatment with atorvastatin and irbesartan, initiated on day 3 after acute ischemic stroke, did not appear to substantially modify infarct growth.

Reducing Haemorrhagic Transformation after Thrombolysis for Stroke: A Strategy Utilising Minocycline

Haemorrhagic transformation (HT) of recently ischaemic brain is a feared complication of thrombolytic therapy that may be caused or compounded by ischaemia-induced activation of matrix metalloproteinases (MMPs). The tetracycline antibiotic minocycline inhibits matrix MMPs and reduces macroscopic HT in rodents with stroke treated with tissue plasminogen activator (tPA). The West Australian Intravenous Minocycline and TPA Stroke Study (WAIMATSS) aims to determine the safety and efficacy of adding minocycline to tPA in acute ischaemic stroke. The WAIMATSS is a multicentre, prospective, and randomised pilot study of intravenous minocycline, 200 mg 12 hourly for 5 doses, compared with standard care, in patients with ischaemic stroke treated with intravenous tPA. The primary endpoint is HT diagnosed by brain CT and MRI. Secondary endpoints include clinical outcome measures. Some illustrative cases from the early recruitment phase of this study will be presented, and future perspectives will be discussed.

Metformin‐induced encephalopathy: the role of thiamine

A case of metformin encephalopathy is presented in a patient on haemodialysis for end‐stage diabetic renal failure. The patient presented with frequent falls and clinical signs of Parkinsonism, on a background of recent anorexia and significant weight loss. Magnetic resonance imaging showed bilateral, symmetrical abnormalities centred on the lentiform nuclei. Metformin was withheld and signs and symptoms quickly resolved. We hypothesise that metformin may cause thiamine deficiency in patients with end‐stage renal failure resulting in a specific metabolic encephalopathy.

Functional magnetic resonance imaging evaluation of lumbosacral radiculopathic pain

OBJECTIVE An objective biomarker for pain is yet to be established. Functional MRI (fMRI) is a promising neuroimaging technique that may reveal an objective radiological biomarker. The purpose of this study was to evaluate fMRI technology in the setting of lumbosacral radiculopathy and discuss its application in revealing a biomarker for pain in the future. METHODS A prospective, within-participant control study was conducted. Twenty participants with painful lumbosacral radiculopathy from intervertebral disc pathology were recruited. Functional imaging of the brain was performed during a randomly generated series of nonprovocative and provocative straight leg raise maneuvers. RESULTS With a statistical threshold set at p < 0.000001, 3 areas showed significant blood oxygen level-dependent (BOLD) signal change: right superior frontal gyrus (x = 2, y = 13, z = 48, k = 29, Brodmann area 6 [BA6]), left supramarginal cortex (x = -37, y = -44, z = 33, k = 1084, BA40), and left parietal cortex (x = -19, y = -41, z = 63, k = 354, BA5). With a statistical threshold set at p < 0.0002, 2 structures showed significant BOLD signal change: right putamen (x = 29, y = -11, z = 6, k = 72) and bilateral thalami (right: x = 23, y = -11, z = 21, k = 29; x = 8, y = -11, z = 9, k = 274; and left: x = -28, y = -32, z = 6, k = 21). CONCLUSIONS The results in this study compare with those in previous studies and suggest that fMRI technology can provide an objective assessment of the pain experience.

Propofol as a substitute for amobarbital in Wada testing

We describe a patient with equivocal findings on functional MRI (fMRI), who underwent a propofol Wada test, review the literature on this topic and suggest a protocol for the use of propofol for a Wada test. Although fMRI techniques can usually accurately lateralize language, the Wada test remains the gold standard for preoperative lateralization and is occasionally still required if there are non-diagnostic findings on fMRI. Amobarbital, the agent of choice for the Wada test, has become increasingly difficult to obtain and requires regulatory approval, which may delay definitive management and have an impact on patient outcomes. Propofol has been suggested as an alternative to amobarbital, and while there is some published data on this, there is no reported Australian experience to date.

Rosette-forming glioneural tumor of the fourth ventricle: Surgery complicated by cerebellar mutism in an elderly patient

Rosette-forming glioneural tumors (RGNT) of the fourth ventricle are rare biphasic tumors comprising both glial and neurocytic elements. It is described as a disease, which mainly affects young adults in the World Health Organisation central nervous system tumor classification. To our knowledge, our patient is the oldest reported patient with RGNT in literature. In this case report, we present an atypical diagnostic age and an infrequent complication related to surgery for this age group. An 81-year-old female presented after an episode of sudden collapse on a 2-month background history of headaches and gait disturbance. On examination, the patient had mild gait ataxia but no focal neurological deficits. Computed tomography of the brain revealed a mixed attenuation intra-axial lesion centered on the cerebellar vermis with associated foci of calcification causing obstructive hydrocephalus. The patient underwent a posterior fossa craniotomy and excision of the lesion through a transvermian approach. The patient was well in the initial postoperative period with no deficits but 1 week later developed cerebellar mutism. RGNT is a rare entity only previously been reported in young adults. Age of diagnosis was noted to be a distinguishing feature of this condition. Our case highlights that the clinicopatholgic characterization of RGNT should be revisited, as these lesions can occur over a broad age group. From a limited number of cases studied to date, RGNT seems to be slow growing and relatively indolent tumor.