David Prentice

Magnesium in cardiac arrest (the magic trial).

The prognosis of out of hospital cardiac arrest (OHCA) is dismal. Recent reports indicate that high dose magnesium may improve survival. A prospective randomized double blind placebo controlled trial was conducted at the emergency department (ED) of Royal Perth Hospital, a University teaching hospital. Patients with OHCA of cardiac origin received either 5 g MgSO4 or placebo as first line drug therapy. The remainder of their management was standard advanced cardiac life support (ACLS). Study endpoints were: (1) ECG rhythm 2 min after the trial drug; (2) return of spontaneous circulation; (3) survival to leave the ED; (4) survival to leave intensive care; and (5) survival to hospital discharge. Of 67 patients enrolled, 31 received magnesium and 36 placebo. There were no significant differences between groups for all criteria, except that there were significantly more arrests witnessed after arrival of EMS personnel in the magnesium group (11 or 35% vs 4 or 11%). Return of spontaneous circulation occurred in seven (23%) patients receiving magnesium and eight (22%) placebo. Four patients in each group survived to leave the ED and one from the magnesium group survived to hospital discharge. There were no survivors in the placebo group. In this study, the use of high dose magnesium as first line drug therapy for OHCA was not associated with a significantly improved survival. Early defibrillation remains the single most important treatment for ventricular fibrillation (VF). Further studies are required to evaluate the role of magnesium in cardiac and cerebral resuscitation.

Intravenous Minocycline in Acute Stroke A Randomized, Controlled Pilot Study and Meta-analysis

Background and Purpose— Minocycline, in animal models and 2 small randomized controlled human trials, is a promising neuroprotective agent in acute stroke. We analyzed the efficacy and safety of intravenous minocycline in acute ischemic and hemorrhagic stroke. Methods— A multicenter prospective randomized open-label blinded end point evaluation pilot study of minocycline 100 mg administered intravenously, commenced within 24 hours of onset of stroke, and continued 12 hourly for a total of 5 doses, versus no minocycline. All participants received routine stroke care. Primary end point was survival free of handicap (modified Rankin Scale, ⩽2) at day 90. Results— Ninety-five participants were randomized; 47 to minocycline and 48 to no minocycline. In the intention-to-treat population, 29 of 47 (65.9%) allocated minocycline survived free of handicap compared with 33 of 48 (70.2%) allocated no minocycline (rate ratio, 0.94; 95% confidence interval, 0.71–1.25 and odds ratio, 0.73; 95% CI, 0.31–1.71). A meta-analysis of the 3 human trials suggests minocycline may increase the odds of handicap-free survival by 3-fold (odds ratio, 2.99; 95% CI, 1.74–5.16) but there was substantial heterogeneity among the trials. Conclusions— In this pilot study of a small sample of acute stroke patients, intravenous minocycline was safe but not efficacious. The study was not powered to identify reliably or exclude a modest but clinically important treatment effect of minocycline. Larger trials would improve the precision of the estimates of any treatment effect of minocycline. Clinical Trial Registration— URL: http://www.anzctr.org.au. Unique identifier: ACTRN12612000237886.

Is intravenous lidocaine clinically effective in acute migraine

We performed a prospective, randomized, double-blind, placebo-controlled trial of intravenous lidocaine (1 mg/kg) in the treatment of acute migraine. Thirteen subjects were randomly allocated to receive intravenous lidocaine and 12 received intravenous normal saline. Subjects scored the intensity of headache and nausea on separate visual analogue scales before the injection and at 10 and 20 min after injection. At 20 min, the mean pain intensity score was 80% of initial intensity in the lidocaine group and 82% in the placebo group. The difference was not statistically significant; at 20 min, the 95% confidence interval for the difference between the two groups in mean percentage of initial pain score was 2 ± 29%. At the dose studied, intravenous lidocaine has, at best, only a modest effect in acute migraine.

Successful treatment of macrophage activation syndrome complicating adult Still disease with anakinra

A previously healthy 20‐year‐old man presented with adult Still disease (ASD). He developed life‐threatening macrophage activation syndrome (MAS), which was refractory to standard immunosuppression but responded dramatically to the IL‐1 receptor antagonist anakinra. Subsequent immunological investigations included assessment of the perforin expression of natural killer (NK) cells and CD8+ T cells, which confirmed MAS.

Anti-NMDA receptor encephalitis associated with ictal asystole

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis usually presents with psychiatric symptoms, behavioural changes, impaired consciousness, seizures and autonomic instability. Ictal asystole is a rare phenomenon associated with complex partial seizures. It is implicated as a potential cause of sudden unexpected death in epilepsy. We report a 41-year-old woman who presented with anti-NMDAR encephalitis. During continuous video electroencephalogram and cardiac monitoring, an episode of ictal asystole was detected. We discuss the potential link between anti-NMDAR encephalitis and ictal asystole. Treatment options for ictal asystole in the setting of anti-NMDAR encephalitis are also discussed.

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.

Cortisol: ACTH ratio to test for primary hypoadrenalism: a pilot study

Introduction A standard short Synacthen test (SST) is the conventional diagnostic test for primary hypoadrenalism. Measuring simultaneous plasma cortisol and adrenocorticotrophin hormone (ACTH) and using the cortisol: ACTH ratio as a first-line test may be safer and more convenient than performing a SST. Methods A retrospective study of 349 patients who had a SST with simultaneous baseline plasma cortisol and ACTH performed between 2005 and 2010 in two separate Australian health centres. The plasma cortisol: ACTH ratio was calculated for each patient and their final diagnosis was determined based on their SST result and a review of their clinical notes. Results Eighteen patients had primary hypoadrenalism, 46 patients had secondary hypoadrenalism and 285 patients had normal adrenal function. All the patients with primary hypoadrenalism had a plasma cortisol: ACTH ratio <3, while none of the patients with normal adrenal function or secondary hypoadrenalism had a cortisol: ACTH ratio <3. Therefore, a cortisol: ACTH ratio <3 had a 100% sensitivity and specificity for the diagnosis of primary hypoadrenalism. Patients with secondary hypoadrenalism had a cortisol: ACTH ratio >3, while subjects with normal adrenal function had a cortisol: ACTH ratio >15. There was overlap in cortisol: ACTH ratios of patients with secondary hypoadrenalism and normal adrenal function. Conclusions Although the cortisol: ACTH ratio predicts primary hypoadrenalism, its value is limited to diagnosing primary hypoadrenalism as it does not distinguish secondary hypoadrenalism from normal adrenal function. Larger prospective studies that include patients with early primary hypoadrenalism are needed to confirm the reliability of plasma cortisol: ACTH ratio as a diagnostic test for primary hypoadrenalism.

Pseudomeningocele induced transient loss of consciousness in Marfan syndrome

Anterior and posterior meningoceles are the severest clinical expression of dural ectasia in patients with Marfan syndrome. Meningoceles and pseudomeningoceles have been reported from either asymptomatic, to causing headache, back pain, leg pain, radiculopathy, constipation and/or urinary symptoms. This article includes a case report of a 31‐year‐old woman, who presented with recurrent transient loss of consciousness thought to be secondary to acute changes in intracranial pressure transmitted from a pseudomeningocele.

Mechanical thrombectomy for anterior circulation stroke: 5-year experience in a statewide service with differences in pretreatment time metrics across two hospitals sites

Objective To audit our institutional mechanical thrombectomy (MT) outcomes for acute anterior circulation stroke and examine the influence of workflow time metrics on patient outcomes. Methods A database of 100 MT cases was maintained throughout May 2010—February 2015 as part of a statewide service provided across two tertiary hospitals (H1 and H2). Patient demographics, stroke and procedural details, blinded angiographic outcomes, and 90-day modified Rankin Scale (mRS) scores were recorded. The following time points in stroke treatment were recorded: stroke onset, hospital presentation, CT imaging, arteriotomy, and recanalization. Statistical analysis of outcomes, predictors of outcome, and differences between the hospitals was carried out. Results Thrombolysis in Cerebral Infarction (TICI) 2b/3 reperfusion was 79%. Forty-nine per cent of patients had good clinical outcomes (mRS 0–2). In a subgroup analysis of 76 patients with premorbid mRS 0–1 and first CT performed ≤4.5 h after stroke onset, 60% had good clinical outcomes. Patient and disease characteristics were matched between the two hospitals. H1 had shorter times between hospital presentation and CT (32 vs 55 min, p=0.01), CT and arteriotomy (33 vs 69 min, p=0.00), and stroke onset and recanalization (198 vs 260 min, p=0.00). These time metrics independently predicted good clinical outcome. Median days spent at home in the first 90 days was greater at H1 (61 vs 8, p=0.04) than at H2. A greater proportion of patients treated at H1 were independent (mRS 0–2) at 90 days (54% vs 42%); however, this was not statistically significant (p=0.22). Conclusions Outcomes similar to randomized controlled trials are attainable in ‘real-world’ settings. Workflow time metrics were independent predictors of clinical outcome, and differed between the two hospitals owing to site-specific organizational differences.

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.