Severe malaria is commonly misdiagnosed in Africa, leading to a failure to treat other life-threatening illnesses. In malaria-endemic areas, parasitemia does not ensure a diagnosis of severe malaria because parasitemia can be incidental to other concurrent disease. The detection of malarial retinopathy is a candidate diagnostic test for cerebral malaria. Malarial retinopathy consists of a set of retinal abnormalities that is unique to severe malaria and common in children with cerebral malaria. Its presence and severity are related to risk of death and length of coma in survivors. A large, prospective autopsy study of children dying with cerebral malaria in Malawi found that malarial retinopathy was better than any other clinical or laboratory feature in distinguishing malarial from non-malarial coma. However, visualization has to date relied on specialist examination techniques. Further studies are planned to evaluate the usefulness of funduscopy by general clinicians in a variety of settings across Africa. Studies of the retina and retinal blood vessels provide an unparalleled opportunity to visualize an infected microvasculature and its effect on neural tissue in vivo. This report reviews current knowledge of malarial retinopathy, including its use as a diagnostic test in the comatose child, and its value as a tool for research into the pathophysiology of cerebral malaria.

/pdf/malarial-retinopathy-a-newly-established-diagnostic-sign-in-lv6lf8yqjt.pdf

Malarial retinopathy: a newly established diagnostic sign in severe malaria

We studied the prognostic strength of the individual components of the Glasgow Coma Scale (GCS) and pupil reactivity to Glasgow Outcome Score (GOS) at 6 months post-injury. A total of 8721 moderate or severe traumatic brain injury (TBI) patient data from the IMPACT database on traumatic brain injury comprised the study cohort. The associations between motor score and pupil reactivity and 6-month GOS were analyzed by binary logistic regression and proportional odds methodology. The strength of prognostic effects were expressed as the unadjusted odds ratios presented for all individual studies as well as in meta-analysis. We found a consistent strong association between motor score and 6-month GOS across all studies (OR 1.74–7.48). The Eye and Verbal components were also strongly associated with GOS. In the pooled population, one or both un-reactive pupils and lower motor scores were significantly associated with unfavorable outcome (range 2.71–7.31). We also found a significant change in motor score from p...

Prognostic value of the Glasgow Coma Scale and pupil reactivity in traumatic brain injury assessed pre-hospital and on enrollment: an IMPACT analysis.

Background : This paper introduces the Neurological Pupil index (NPi), a sensitive measure of pupil reactivity and an early indicator of increasing intracranial pressure (ICP). This may occur in patients with severe traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage (ICH). Methods : 134 patients (mean age 46 years, range 18-87 years, 54 women and 80 men) in the intensive care units at eight different clinical sites were enrolled in the study. Pupillary examination was performed using a portable hand-held pupillometer. Results : Patients with abnormal pupillary light reactivity had an average peak ICP of 30.5 mmHg versus 19.6 mmHg for the normal pupil reactivity population ( P = 0.0014). Patients with nonreactive pupils had the highest peaks of ICP (mean = 33.8 mmHg, P = 0.0046). In the group of patients with abnormal pupillary reactivity, we found that the first evidence of pupil abnormality occurred, on average, 15.9 hours prior to the time of the peak of ICP. Conclusions : Automated pupillary assessment was used in patients with possible increased ICP. Using NPi, we were able to identify a trend of inverse relationship between decreasing pupil reactivity and increasing ICP. Quantitative measurement and classification of pupillary reactivity using NPi may be a useful tool in the early management of patients with causes of increased ICP.

Pupillary reactivity as an early indicator of increased intracranial pressure: The introduction of the Neurological Pupil index

Portable infrared pupillometers provide an objective measure of pupil size and pupillary reflexes, which for most clinicians was previously only a visual impression. But despite the fact that pupillometry can uncover aspects of how the human pupil reacts to drugs and noxious stimulation, the use of pupillometry has not gained widespread use among anesthesiologists and critical care physicians. The present review is an introduction to the physiology of pupillary reflexes and the currently established clinical applications of infrared pupillometry, which will hopefully encourage physicians to use this diagnostic tool in their clinical practice. Portable infrared pupillometry was introduced in 1989. The technology involves flooding the eye with infrared light and then measuring the reflected image on an infrared sensor. Pupil size, along with variables of the pupillary light reflex and pupillary reflex dilation, is calculated by the instrument and displayed on a screen immediately after each time-stamped measurement. Use of these instruments has uncovered aspects of how the human pupil reacts to drugs and noxious stimulation. The primary clinical applications for portable pupillometry have been in the assessment of brainstem function. Portable pupillometry is useful in the management of pain because it allows for assessments of the effect of opioids and in the titration of combined regional-general anesthetics.

Portable infrared pupillometry: a review.

Following traumatic brain injury (TBI), the cytoskeletal protein α-II-spectrin is proteolyzed by calpain and caspase-3 to signature breakdown products. To determine whether α -II-spectrin proteolysis is a potentially reliable biomarker for TBI in humans, the present study (1) examined levels of spectrin breakdown products (SBDPs) in cerebrospinal fluid (CSF) from adults with severe TBI and (2) examined the relationship between these levels, severity of injury, and clinical outcome. This prospective case control study enrolled 41 patients with severe TBI, defined by a Glasgow Coma Scale (GCS) score of ≤8, who underwent intraventricular intracranial pressure monitoring. Patients without TBI requiring CSF drainage for other medical reasons served as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, and 120 h following TBI and analyzed for SBDPs. Outcome was assessed using the Glasgow Outcome Score (GOS) 6 months after injury. Calpain and caspase-3 mediated SBDP levels in CSF w...

/pdf/clinical-significance-of-aii-spectrin-breakdown-products-in-389vy4ez95.pdf

Clinical Significance of αII-Spectrin Breakdown Products in Cerebrospinal Fluid after Severe Traumatic Brain Injury

Adaptive optics (AO), a mature technology developed for astronomy to compensate for the effects of atmospheric turbulence, can also be used to correct the aberrations of the eye. The classic phoropter is used by ophthalmologists and optometrists to estimate and correct the lower-order aberrations of the eye, defocus and astigmatism, in order to derive a vision correction prescription for their patients. An adaptive optics phoropter measures and corrects the aberrations in the human eye using adaptive optics techniques, which are capable of dealing with both the standard low-order aberrations and higher-order aberrations, including coma and spherical aberration. High-order aberrations have been shown to degrade visual performance for clinical subjects in initial investigations. An adaptive optics phoropter has been designed and constructed based on a Shack-Hartmann sensor to measure the aberrations of the eye, and a liquid crystal spatial light modulator to compensate for them. This system should produce near diffraction-limited optical image quality at the retina, which will enable investigation of the psychophysical limits of human vision. This paper describes the characterization and operation of the AO phoropter with results from human subject testing.

/pdf/characterization-and-operation-of-a-liquid-crystal-adaptive-2wedh74iss.pdf

Characterization and operation of a liquid crystal adaptive optics phoropter

We discuss the design and implementation of a low-cost, high-resolution adaptive optics test-bed for vision research. It is well known that high-order aberrations in the human eye reduce optical resolution and limit visual acuity. However, the effects of aberration-free eyesight on vision are only now beginning to be studied using adaptive optics to sense and correct the aberrations in the eye. We are developing a high-resolution adaptive optics system for this purpose using a Hamamatsu Parallel Aligned Nematic Liquid Crystal Spatial Light Modulator. Phase-wrapping is used to extend the effective stroke of the device, and the wavefront sensing and wavefront correction are done at different wavelengths. Issues associated with these techniques will be discussed.

/pdf/high-resolution-adaptive-optics-test-bed-for-vision-science-45dvbbvpvy.pdf

High-resolution adaptive optics test bed for vision science

A High-Resolution Adaptive Optics System for Vision Science

OBJECTIVE: Acute pupillary dilation in a head-injured patient is a neurological emergency. Pupil dilation is thought to be the result of uncal herniation causing mechanical compression of the IIIrd cranial nerve and subsequent brain stem compromise. However, not all patients with herniation have fixed and dilated pupils, and not all patients with nonreactive, enlarged pupils have uncal herniation. Therefore, we have tested an alternative hypothesis that a decrease in brain stem blood flow (BBF) is a more frequent cause of mydriasis and brain stem symptomatology after severe head injury. We determined the relation of BBF to outcome and pupillary response in patients with severe head injuries. METHODS: One hundred sixty-two patients with a Glasgow Coma Scale score of 8 or less underwent stable xenon computed tomographic blood flow determination at the level of the superior colliculus, and this blood flow was correlated with pupillary features, intracranial pressure, computed tomographic scan pathology, and outcome. RESULTS: A BBF of less than 40 ml/100 g/min was significantly associated with poor outcome (P < 0.009). In patients with bilaterally nonreactive pupils, the BBF was 30.5+/-16.8 ml/100 g/min, and in those with normally reactive pupils, the BBF was 43.8+/-18.7 ml/100 g/min (P < 0.001). Intracranial pressure and the presence of a brain stem lesion observed on the computed tomographic scan did not correlate with BBF, pupillary size, or reactivity. Unfavorable outcome at 12 months was directly related to age (P = 0.062) and inversely related to pupillary responsiveness (P = 0.0006), pupil size (P = 0.005), and BBF of less than 40 ml/100 g/min (P = 0.009). CONCLUSION: These findings suggest that pupillary dilation is associated with decreased BBF and that ischemia, rather than mechanical compression of the IIIrd cranial nerve, is an important causal factor. More important, pupil dilation may be an indicator of ischemia of the brain stem. If cerebral blood flow and cerebral perfusion pressure can be rapidly restored in the patient with severe head injury who has dilated pupils, the prognosis may be good.

Brain stem blood flow, pupillary response, and outcome in patients with severe head injuries.

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Characterization and operation of a liquid crystal adaptive optics phoropter

High-resolution adaptive optics test bed for vision science

A High-Resolution Adaptive Optics System for Vision Science

Brain stem blood flow, pupillary response, and outcome in patients with severe head injuries.