Clinicians routinely check the pupils of critically injured and ill patients to monitor neurological status. However, manual pupil measurements (performed using a penlight or ophthalmoscope) have been shown to be subjective, inaccurate, and not repeatable or consistent. [1] Automated assessment of the pupillary light reflex has emerged as an objective means of measuring pupillary reactivity across a range of neurological diseases, including stroke, traumatic brain injury and edema, tumoral herniation syndromes, and sports or war injuries. Automated pupillometers are used to assess an array of objective pupillary variables including size, constriction velocity, latency, and dilation velocity, which are normalized and standardized to compute an indexed score such as the Neurological Pupil index (NPi) or the Quantitative Pupillometry index (QPi).
Pupillary evaluation involves the assessment of two components—pupil size and reactivity to light.
The Neurological Pupil index, or NPi, is an algorithm developed by NeurOptics, Inc., that removes subjectivity from the pupillary evaluation. A patient's pupil measurement (including variables such as size, latency, constriction velocity, dilation velocity, etc.) is obtained using a pupillometer, and the measurement is compared against a normative model of pupil reaction to light and automatically graded by the NPi on a scale of 0 to 4.9. Pupil reactivity is express numerically so that changes in both pupil size and reactivity can be trended over time, just like other vital signs.
The numeric scale of the NPi allows for a more rigorous interpretation and classification of the pupil response than subjective assessment.
Each NPi measurement taken is rated on a scale ranging from 0 to 4.9. A score equal to or above 3 means that the pupil measurement falls within the boundaries of normal pupil behavior as defined by the NPi. However, a value closer to 4.9 is more normal data than a value closer to 3. An NPi score below 3 means the reflex is abnormal, i.e., weaker than a normal pupil response, and values closer to 0 are more abnormal than values closer to 3. A difference in NPi between Right and Left pupils of greater than or equal to 0.7 may also be considered an abnormal pupil reading.
More than 100 studies published in peer-reviewed academic journals indicate the effectiveness of automated pupillometry and the NPi scale for use in critical care medicine, neurology, neurosurgery, emergency medicine, and applied research settings.
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Several clinical publications have demonstrated the clinical equivalence of the QPi (Quantitative Pupillary Index) and NPi (Neurological Pupillary Index) in critical care settings. These indices have been studied in various contexts, including the assessment of comatose patients following cardiac arrest (CA) and the evaluation of traumatic brain injury (TBI).
The first abstract, titled "Comparison between Neurological Pupil Index and Quantitative Pupillometry Index to prognosticate outcome after cardiac arrest", by Pasetto et al., investigated the prognostic accuracy of QPi and NPi in predicting unfavorable neurological outcomes after CA. This prospective observational study revealed significant correlations between QPi and NPi values. The study concluded that both indices are interchangeable for assessing neurological outcomes in CA patients, further supporting their reliability in clinical practice.
A second abstract, "Equivalence between Quantitative Pupillary Index (QPi) and Neurological Pupil Index (NPi) in Critical Care Settings" , by Blandino Ortiz et al., also highlighted the equivalence of the two indices across diverse neurocritical applications. This study demonstrated that QPi and NPi provide strongly correlated results when used to monitor pupillary reactivity, reinforcing their role as reliable tools for early decision-making in neurocritical care.
A third abstract, "Quantitative Pupillometry Index (QPi) in Comatose Patients After Cardiac Arrest", by Zorzi et al., expanded on these findings by evaluating the QPi and NPi in a larger cohort of 98 patients across two centers. This study showed strong correlations between the indices over multiple time points (e.g., Ps = 0.70 at 24 hours, Ps = 0.68 at 72 hours, p < 0.001). A QPi ≤ 2 at 72 hours demonstrated a specificity of 100% for predicting UO, further underscoring its prognostic value. The authors concluded that QPi and NPi are strongly correlated and can be interchangeably used for prognosticating neurological outcomes in comatose patients after CA.
Together, these studies reinforce the equivalence and utility of QPi and NPi as interchangeable tools in critical care, particularly for monitoring pupillary reactivity and predicting neurological outcomes in patients with acute brain injuries or post-cardiac arrest comas.
Brain death is the permanent, irreversible, and complete loss of brain function, which may include cessation of involuntary activity necessary to sustain life. It differs from persistent vegetative state, in which the person is alive and some autonomic functions remain. It is also distinct from comas as long as some brain and bodily activity and function remain, and it is also not the same as the condition locked-in syndrome. A differential diagnosis can medically distinguish these differing conditions.
Cerebral edema is excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compression of brain tissue and blood vessels. Symptoms vary based on the location and extent of edema and generally include headaches, nausea, vomiting, seizures, drowsiness, visual disturbances, dizziness, and in severe cases, death.
Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of consciousness, fever, weakness, numbness, and sometimes seizures. Neck stiffness or neck pain are also relatively common. In about a quarter of people a small bleed with resolving symptoms occurs within a month of a larger bleed.
A subdural hematoma (SDH) is a type of bleeding in which a collection of blood—usually but not always associated with a traumatic brain injury—gathers between the inner layer of the dura mater and the arachnoid mater of the meninges surrounding the brain. It usually results from rips in bridging veins that cross the subdural space.
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity ranging from mild traumatic brain injury (mTBI/concussion) to severe traumatic brain injury. TBI can also be characterized based on mechanism or other features. Head injury is a broader category that may involve damage to other structures such as the scalp and skull. TBI can result in physical, cognitive, social, emotional and behavioral symptoms, and outcomes can range from complete recovery to permanent disability or death.
An induced coma – also known as a medically induced coma (MIC), barbiturate-induced coma, or drug-induced coma – is a temporary coma brought on by a controlled dose of an anesthetic drug, often a barbiturate such as pentobarbital or thiopental. Other intravenous anesthetic drugs such as midazolam or propofol may be used.
Intracerebral hemorrhage (ICH), also known as hemorrhagic stroke, is a sudden bleeding into the tissues of the brain, into its ventricles, or into both. An ICH is a type of bleeding within the skull and one kind of stroke. Symptoms can vary dramatically depending on the severity, acuity, and location (anatomically) but can include headache, one-sided weakness, numbness, tingling, or paralysis, speech problems, vision or hearing problems, memory loss, attention problems, coordination problems, balance problems, dizziness or lightheadedness or vertigo, nausea/vomiting, seizures, decreased level of consciousness or total loss of consciousness, neck stiffness, and fever.
Pupillometer, also spelled pupilometer, is a medical device intended to measure by reflected light the size of the pupil of the eye. In addition to measuring pupil size, current automated pupillometers may also be able to characterize pupillary light reflex. Some instruments for measuring pupillary distance (PD) are often, but incorrectly, referred to as pupilometers.
Decompressive craniectomy is a neurosurgical procedure in which part of the skull is removed to allow a swelling or herniating brain room to expand without being squeezed. It is performed on victims of traumatic brain injury, stroke, Chiari malformation, and other conditions associated with raised intracranial pressure. Use of this surgery is controversial.
Targeted temperature management (TTM), previously known as therapeutic hypothermia or protective hypothermia, is an active treatment that tries to achieve and maintain a specific body temperature in a person for a specific duration of time in an effort to improve health outcomes during recovery after a period of stopped blood flow to the brain. This is done in an attempt to reduce the risk of tissue injury following lack of blood flow. Periods of poor blood flow may be due to cardiac arrest or the blockage of an artery by a clot as in the case of a stroke.
Neurocritical care is a medical field that treats life-threatening diseases of the nervous system and identifies, prevents, and treats secondary brain injury.
An external ventricular drain (EVD), also known as a ventriculostomy or extraventricular drain, is a device used in neurosurgery to treat hydrocephalus and relieve elevated intracranial pressure when the normal flow of cerebrospinal fluid (CSF) inside the brain is obstructed. An EVD is a flexible plastic catheter placed by a neurosurgeon or neurointensivist and managed by intensive care unit (ICU) physicians and nurses. The purpose of external ventricular drainage is to divert fluid from the ventricles of the brain and allow for monitoring of intracranial pressure. An EVD must be placed in a center with full neurosurgical capabilities, because immediate neurosurgical intervention can be needed if a complication of EVD placement, such as bleeding, is encountered.
Midline shift is a shift of the brain past its center line. The sign may be evident on neuroimaging such as CT scanning. The sign is considered ominous because it is commonly associated with a distortion of the brain stem that can cause serious dysfunction evidenced by abnormal posturing and failure of the pupils to constrict in response to light. Midline shift is often associated with high intracranial pressure (ICP), which can be deadly. In fact, midline shift is a measure of ICP; presence of the former is an indication of the latter. Presence of midline shift is an indication for neurosurgeons to take measures to monitor and control ICP. Immediate surgery may be indicated when there is a midline shift of over 5 mm. The sign can be caused by conditions including traumatic brain injury, stroke, hematoma, or birth deformity that leads to a raised intracranial pressure.
Increased intracranial pressure (ICP) is one of the major causes of secondary brain ischemia that accompanies a variety of pathological conditions, most notably traumatic brain injury (TBI), strokes, and intracranial hemorrhages. It can cause complications such as vision impairment due to intracranial pressure (VIIP), permanent neurological problems, reversible neurological problems, seizures, stroke, and death. However, aside from a few Level I trauma centers, ICP monitoring is rarely a part of the clinical management of patients with these conditions. The infrequency of ICP can be attributed to the invasive nature of the standard monitoring methods. Additional risks presented to patients can include high costs associated with an ICP sensor's implantation procedure, and the limited access to trained personnel, e.g. a neurosurgeon. Alternative, non-invasive measurement of intracranial pressure, non-invasive methods for estimating ICP have, as a result, been sought.
The Mischer Neuroscience Institute is a combined research and education effort between the Vivian L. Smith Department of Neurosurgery and the Department of Neurology at McGovern Medical School at UTHealth Houston and Memorial Hermann Hospital. Located in Houston, the Institute draws patients from around the world for specialized treatment of diseases of the brain and spine. It was the first center in Texas and one of only a few institutions in the country to fully integrate neurology, neurosurgery, neuroradiology, neuro-oncology, spine surgery, pain medicine and neurorehabilitation.
Pupillometry, the measurement of pupil size and reactivity, is a key part of the clinical neurological exam for patients with a wide variety of neurological injuries. It is also used in psychology.
The Glasgow Outcome Scale (GOS) is an ordinal scale used to assess functional outcomes of patients following brain injury. It considers several factors, including a patient's level of consciousness, ability to carry out activities of daily living (ADLs), and ability to return to work or school. The scale provides a structured way to classify patient outcomes into five broad categories: death, vegetative state, severe disability, moderate disability, or good recovery.
John Douglas Pickard is a British professor emeritus of neurosurgery in the Department of Clinical Neurosciences of University of Cambridge. He is the honorary director of the National Institute for Health Research (NIHR) Healthcare Technology Cooperative (HTC) for brain injury. His research focuses on advancing the care of patients with acute brain injury, hydrocephalus and prolonged disorders of consciousness through functional brain imaging, studies of pathophysiology and new treatments; as well as focusing on health, economic and ethical aspects.
Pressure reactivity index or PRx is a tool for monitoring cerebral autoregulation in the intensive care setting for patients with severe traumatic brain injury or subarachnoid haemorrhage, in order to guide therapy to protect the brain from dangerously high or low cerebral blood flow.
Stephan A. Mayer is an American neurologist and critical care physician who currently serves as Director of Neurocritical Care and Emergency Neurology Services for the Westchester Medical Center Health System. Mayer is most noted for his research in subarachnoid and intracerebral hemorrhage, acute ischemic stroke, cardiac arrest, coma, status epilepticus, brain multimodality monitoring, therapeutic temperature modulation, and outcomes after severe brain injury. He has gained media attention for popularizing the concept that physicians have historically underestimated the brain’s resilience and capacity for recovery. He has authored over 400 original research publications, 200 chapters and review articles, and 370 abstracts.