Eusebia Calvillo

Marked olfactory impairment in idiopathic intracranial hypertension

Objective Many long-duration astronauts develop signs of elevated intracranial pressure and have neuro-ophthalmological findings similar to idiopathic intracranial hypertension (IIH) patients. Some also present with nasal congestion and subjective olfactory impairment. We prospectively evaluated olfactory function in IIH patients and the effect of 6° head-down tilt, which simulates the headward fluid shifting in microgravity, as spaceflight analogues. Design Olfaction was tested for all subjects in upright and 6° head-down tilt positions using two different measures: University of Pennsylvania Smell Identification Test and Olfactory Threshold Sniffin’ Sticks with phenylethyl alcohol. Results IIH patients (n=19) had significant impairment on both olfactory measures compared with matched controls (n=19). The olfactory threshold dilution levels were 9.07 (95% CI 1.85 to 5.81) and 3.83 (95% CI 7.04 to 11.10), p=0.001, and smell identification scores were 35.61 (95% CI 34.03 to 37.18) and 32.47 (95% CI 30.85 to 34.09), p=0.008, for control and IIH subjects, respectively. The threshold detection was mildly impaired in head-down tilt compared with upright position in the combined subjects (6.05 (95% CI 4.58 to 7.51) vs 6.85 (95% CI 5.43 to 8.27), p=0.004). Conclusions We demonstrated that IIH patients have marked impairment in olfactory threshold levels, out of proportion to smell identification impairment. There was also impairment in olfactory threshold in head-down tilt compared with upright positioning, but not for smell identification. The underlying mechanisms for olfactory threshold dysfunction in IIH patients need further exploration.

Intracranial pressure modulates distortion product otoacoustic emissions: a proof-of-principle study.

BACKGROUND There is an important need to develop a noninvasive method for assessing intracranial pressure (ICP). We report a novel approach for monitoring ICP using cochlear-derived distortion product otoacoustic emissions (DPOAEs), which are affected by ICP. OBJECTIVE We hypothesized that changes in ICP may be reflected by altered DPOAE responses via an associated change in perilymphatic pressure. METHODS We measured the ICP and DPOAEs (magnitude and phase angle) during opening and closing in 20 patients undergoing lumbar puncture. RESULTS We collected data on 18 patients and grouped them based on small (<4 mm Hg), medium (5-11 mm Hg), or large (≥15 mm Hg) ICP changes. A permutation test was applied in each group to determine whether changes in DPOAEs differed from zero when ICP changed. We report significant changes in the DPOAE magnitudes and angles, respectively, for the group with the largest ICP changes and no changes for the group with the smallest changes; the group with medium changes had variable DPOAE changes. CONCLUSION We report, for the first time, systematic changes in DPOAE magnitudes and phase in response to acute ICP changes. Future studies are warranted to further develop this new approach. ABBREVIATIONS DPOAE, distortion product otoacoustic emissionICP, intracranial pressureIIH, idiopathic intracranial hypertensionLP, lumbar punctureTBI, traumatic brain injury.

Optical coherence tomography of the optic nerve head detects acute changes in intracranial pressure.

We aimed to determine if there are measurable objective changes in the optic nerve head (ONH) immediately after cerebrospinal fluid (CSF) drainage in a prospective case-series of five patients undergoing a clinically indicated lumbar puncture (LP) for diagnosis of idiopathic intracranial hypertension. A Cirrus high-definition optical coherence tomography machine (Carl Zeiss Meditec, Dublin, CA, USA) was used to acquire images in the lateral decubitus position. Optic disc cube and high-definition line raster scans centered on the ONH were obtained immediately before and after draining CSF, while the patient maintained the lateral decubitus position. Measured parameters included retinal nerve fiber layer (RNFL) thickness, peripapillary retinal pigment epithelium/Bruchs membrane (RPE/BM) angulation, transverse neural canal diameter (NCD) and the highest vertical point of the internal limiting membrane from the transverse diameter (papillary height). The mean (±standard deviation) opening and closing CSF pressures were 34.3±11.8 and 11.6±3.3cmH2O, respectively. Mean RNFL thickness (pre LP: 196±105μm; post LP: 164±77μm, p=0.1) and transverse NCD (pre LP: 1985±559μm; post LP: 1590±228μm, p=2.0) decreased in all subjects, but with non-significant trends. The RPE/BM angle (mean change: 5.8±2.0degrees, p=0.003) decreased in all subjects. A decrease in papillary height was seen in three of five subjects (mean: pre LP: 976±275μm; post LP: 938±300μm, p=0.9). Our results show a measurable, objective change in the ONH after acute lowering of the lumbar CSF pressure, suggesting a direct link between the lumbar subarachnoid space and ONH regions, and its potential as a non-invasive method for monitoring intracranial pressures.

Effect of human albumin on TCD vasospasm, DCI, and cerebral infarction in subarachnoid hemorrhage: the ALISAH study.

BACKGROUND AND PURPOSE The neuroprotective effects of human albumin have been studied in animal models of stroke and in humans with various intracranial disorders. We investigated the effect of 25 % human albumin (ALB) on mean cerebral blood flow velocities (MCBFV), delayed cerebral ischemia (DCI), and cerebral infarction. METHODS We studied patients from the Albumin in Subarachnoid Hemorrhage (ALISAH) pilot clinical trial. We collected data on MCBFV as measured by transcranial Doppler ultrasound (TCD), incidence of DCI, and cerebral infarctions on head computed tomography (CT) scan at 90 days. RESULTS TCD showed vasospasm in 75 % (n = 15), 55 % (n = 11), and 29 % (n = 2) of subjects in dosage tiers 1, 2, and 3, respectively. DCI was present in 20 % (n = 4), 15 % (n = 3), and 14 % (n = 1) of subjects in dosage tiers 1, 2, and 3, respectively. Cerebral infarctions were seen in 45 % (5 of 9), 27 % (3 of 18), and 25 % (1 of 4) of subjects who had follow-up head CT scans in dosage tiers 1, 2, and 3, respectively. CONCLUSIONS Higher dosages of ALB were associated with a lower incidence of TCD vasospasm, DCI, and cerebral infarction at 90 days in a dose-dependent manner.

Human Albumin Use in Adults in U.s. Academic Medical Centers.

Objective: To determine rates and predictors of albumin administration, and estimated costs in hospitalized adults in the United States. Design: Cohort study of adult patients from the University HealthSystem Consortium database from 2009 to 2013. Setting: One hundred twenty academic medical centers and 299 affiliated hospitals. Patients: A total of 12,366,264 hospitalization records. Interventions: Analysis of rates and predictors of albumin administration, and estimated costs. Measurements and Main Results: Overall the proportion of admissions during which albumin was administered increased from 6.2% in 2009 to 7.5% in 2013; absolute difference 1.3% (95% CI, 1.30–1.40%; p < 0.0001). The increase was greater in surgical patients from 11.7% in 2009 to 15.1% in 2013; absolute difference 3.4% (95% CI, 3.26–3.46%; p < 0.0001). Albumin use varied geographically being lowest with no increase in hospitals in the North Eastern United States (4.9% in 2009 and 5.3% in 2013) and was more common in bigger (> 750 beds; 5.2% in 2009 and 7.3% in 2013) compared to smaller hospitals (< 250 beds; 4.4% in 2009 to 6.2% in 2013). Factors independently associated with albumin use were appropriate indication for albumin use (odds ratio, 65.220; 95% CI, 62.459–68.103); surgical admission (odds ratio, 7.942; 95% CI, 7.889–7.995); and high severity of illness (odds ratio, 8.933; 95% CI, 8.825–9.042). Total estimated albumin cost significantly increased from

Adult Moyamoya Disease in an Urban Center in the United States Is Associated With a High Burden of Watershed Ischemia

325 million in 2009 to

Inflammatory gene expression signatures in idiopathic intracranial hypertension: possible implications in microgravity-induced ICP elevation

468 million in 2013; (absolute increase of

Internal Jugular Vein Volume During Head-Down Tilt and Carbon Dioxide Exposure in the SPACECOT Study

233 million), p value less than 0.0001. Conclusions: The proportion of hospitalized adults in the United States receiving albumin has increased, with marked, and currently unexplained, geographic variability and variability by hospital size.

Human Albumin Administration in Subarachnoid Hemorrhage: Results of an International Survey

Background Adult moyamoya disease is rare in the United States, and patients mostly present with cerebral ischemia. However, clinical and neurodiagnostic correlates of ischemia are not well known in this population. We sought to characterize the clinical and radiographic features of moyamoya disease in a large urban center in the United States, with a focus on angiographic and neuroimaging patterns of ischemia. Methods and Results We retrospectively reviewed charts of consecutive adult moyamoya disease patients evaluated at 2 centers in Houston, Texas from January 2002 to December 2011. We reviewed all available cerebral angiograms and neuroimaging studies to evaluate the Suzuki grades, presence of intracranial hemorrhage or ischemia, infarct patterns, and vascular territory distribution. Our analysis was mainly descriptive. We identified 31 adults with moyamoya disease who met our inclusion criteria. The female‐to‐male ratio was 2.4:1. The majority of patients were white, followed by Hispanic, black, and Asian. Most presented with ischemia (61%), followed by headaches, and intracranial hemorrhage. Of the 22 patients with available neuroimaging, 72.7% had ischemic findings, with the vast majority having a watershed pattern (81.3%). Conclusions We observed a high burden of ischemia, mostly watershed pattern on neuroimaging in our adult moyamoya disease patients. Long‐term monitoring of adult moyamoya disease patients in the United States would be useful to better understand the natural history of this condition.

Clinical Validation of a Transcranial Doppler-Based Noninvasive Intracranial Pressure Meter: A Prospective Cross-Sectional Study

The visual impairment and intracranial pressure (VIIP) syndrome is a neuro–ophthalmologic condition described in astronauts returning from long duration space missions. Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is characterized by a chronic elevation of intracranial pressure (ICP) in the absence of an intracranial mass lesion. Because VIIP and IIH share some neurologic and ophthalmologic manifestations, the latter might be used as a model to study some of the processes underlying VIIP. This work constitutes a preliminary investigation of the molecular pathways associated with the elevation of ICP in IIH. Gene expression signatures were obtained from exosomes collected from CSF and plasma in patients with possible signs of IIH. The gene expression targets focused on inflammatory genes and miRNAs. The results suggest that inflammatory cytokine-driven processes and immune cell migration are activated when ICP is elevated in IIH patients, either as a cause or effect of the ICP increase. Several miRNAs appear to be involved in this response, among which miR-9 and miR-16 are upregulated in CSF and plasma of higher ICP subjects. This study provides evidence in support of neurophysiological alterations and neuro-immunomodulation in this condition. If similar changes are seen in astronauts manifesting with the VIIP syndrome, an underlying pathophysiological basis may be discovered.Vision: Brain inflammation could explain astronauts’ visual impairmentsPeople with elevated pressure inside their skulls show signs of inflammation that could be relevant for astronauts on long-duration missions. To better understand the biology of spaceflight-induced visual impairment—a common problem for astronauts that is thought to arise from pressure building up around the brain in microgravity—a team led by Susana Zanello from the NASA Johnson Space Center in Houston, Texas, USA, examined the spinal fluid and blood of individuals with idiopathic intracranial hypertension, a neurologic condition that shares some features with the mysterious syndrome that impairs astronauts’ sight vision. The researchers characterized the RNA contained within tiny secreted particles, known as exosomes, in the patient samples. The expression of several genes and regulatory microRNAs linked to pro-inflammatory immune responses were changed. The authors surmise that similar immune changes could underpin the eyesight syndrome plaguing astronauts.