Wiley R. Hall

Rapid Unexpected Brain Herniation in Association with Renal Replacement Therapy in Acute Brain Injury: Caution in the Neurocritical Care Unit

IntroductionWe aim to raise awareness for the potential for rapid brain edema and herniation in acutely brain-injured patients undergoing renal replacement therapy (RRT), including one case undergoing continuous veno-venous hemofiltration. Dialysis disequilibrium syndrome (DDS) may have been a possible cause for the brain edema.MethodsWe retrospectively reviewed four consecutive neurocritically ill patients in acute renal failure undergoing RRT between 2011 and 2013. Imaging, blood pressure, and laboratory data pre-, during, and post-RRT are presented in graphical form. We performed an extensive literature review.ResultsAll patients suffered rapidly progressive herniation and death from global brain edema closely related in time to RRT, without other identifiable causes even after detailed review by three neurointensivists. Common clinical symptoms included sudden onset fixed and dilated pupils with apnea, consistent with brain stem compression. Herniation was not reversed by high-dose osmotherapy, and all patients died. Our detailed literature review provides plausible mechanisms for DDS as the most likely cause for our patients’ brain edema.ConclusionsEven today, sudden brain edema and herniation may occur in association with RRT in neurocritically ill patients. We call for the establishment of RRT guidelines in patients with acute neurological injuries.

Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial

Background Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) in human aneurysmal subarachnoid haemorrhage (aSAH). We evaluated safety, feasibility and tolerability of intravenous dantrolene (IV-D) in patients with aSAH. Methods In this single-centre, randomised, double blind, placebo-controlled trial, 31 patients with aSAH were randomised to IV-D 1.25 mg every 6 h for 7 days (n=16) or equiosmolar free water/5% mannitol (placebo; n=15). Primary safety end points were incidence of hyponatraemia (sNa≤132 mmol/L) and liver toxicity (proportion of patients alanine transaminase, aspartate aminotransferase and AlkPhos >5× upper-limit-of-normal). Secondary end points included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored for clinical/radiological cVSP, delayed cerebral ischaemia (DCI), and 3-month functional outcomes. Quantitative analyses of angiograms and daily transcranial Doppler (TCD) were performed. Results Between IV-D versus placebo, no differences were observed in the primary outcomes (hyponatremia 44% vs 67% (p=0.29); liver toxicity 6% vs 0% (p=1.0)). Three patients in the IV-D versus two in the placebo group had severe adverse events possibly attributable to infusion and reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain oedema requiring osmotherapy. The majority of adverse events were not related to infusion (17 vs 5 (RR 2.2; 95% CI 0.7 to 6.7; p=0.16) in IV-D vs placebo). No differences in any categorical cVSP outcomes, DCI, 3-month outcomes or quantitative angiogram and TCD analyses were seen in this small safety trial not powered to detect efficacy. Conclusions In this small trial, IV-D after aSAH was feasible, tolerable and safe. Trial registration number http://clinicaltrials.gov NCT01024972.

“don’t lose hope early”: Hemorrhagic diffuse axonal injury on head Ct is not associated with poor outcome in moderate-severe Tbi patients

BACKGROUND Diffuse axonal injury (DAI) on magnetic resonance imaging has been associated with poor functional outcome after moderate-severe traumatic brain injury (msTBI). Yet, DAI assessment with highly sensitive magnetic resonance imaging techniques is unfeasible in the acute trauma setting, and computed tomography (CT) remains the key diagnostic modality despite its lower sensitivity. We sought to determine whether CT-defined hemorrhagic DAI (hDAI) is associated with discharge and favorable 3- and 12-month functional outcome (Glasgow Coma Scale score ≥4) after msTBI. METHODS We analyzed 361 msTBI patients from the single-center longitudinal Outcome Prognostication in Traumatic Brain Injury study collected over 6 years (November 2009 to November 2015) with prospective outcome assessments at 3 months and 12 months. Patients with microhemorrhages on CT were designated “CT-hDAI-positive” and those without as “CT-hDAI-negative.” For secondary analyses “CT-hDAI-positive” was stratified into two phenotypes according to presence (“associated”) versus absence (“predominant”) of concomitant large acute traumatic lesions to determine whether presence versus absence of additional focal mass lesions portends a different prognosis. RESULTS Seventy (19%) patients were CT-hDAI–positive (n = 36 predominant; n = 34 associated hDAI). In univariate analyses, CT-hDAI–positive status was associated with discharge survival (p = 0.004) and favorable outcome at 3 months (p = 0.003) and 12 months (p = 0.005). After multivariable adjustment, CT-hDAI positivity was no longer associated with discharge survival and functional outcome (all ps > 0.05). Stratified by hDAI phenotype, predominant hDAI patients had worse trauma severity, longer intensive care unit stays, and more systemic medical complications. Predominant hDAI, but not associated hDAI, was an independent predictor of discharge survival (adjusted odds ratio, 24.7; 95% confidence interval [CI], 3.2–192.6; p = 0.002) and favorable 12-month outcome (adjusted odds ratio, 4.7; 95% CI, 1.5–15.2; p = 0.01). Sensitivity analyses using Cox regression confirmed this finding for 1-year survival (adjusted hazard ratio, 5.6; 95% CI, 1.3–23; p = 0.048). CONCLUSION The CT-defined hDAI was not an independent predictor of unfavorable short- and long-term outcomes and should not be used for acute prognostication in msTBI patients. Predominant hDAI patients had good clinical outcomes when supported to intensive care unit discharge and beyond. LEVEL OF EVIDENCE Prognostic study, level III.

Ascending paralysis from malignant leptomeningeal melanomatosis

A 32-year-old male with a past medical history of genital herpes and a 1 week history of headaches, presented with nausea, vomiting and diarrhoea, and had a generalised tonic–clonic seizure. His temperature was 38.1°C and CSF laboratory values were: 14 white blood cells (WBC) (100% monocytes), 16 red blood cells, protein 498 mg/dl and glucose 86 mg/dl; serum WBC 12.7 with 75% neutrophils ( polymorphonuclear leucocytes ). T1 weighted MRI with gadolinium revealed patchy enhancement of the meninges (figure 1A). Serum herpes simplex virus IgG was positive. Viral, herpes simplex virus and bacterial CSF cultures were negative. Acyclovir was started empirically. Two weeks later he suddenly became unresponsive. MRI revealed worsening meningea/temporal lobe enhancement and hydrocephalus (figure 1B). Serum WBC was …