Methods and kits for assessing central nervous system integrity
Inventors
Samadani, Uzma • Offen, Shani • Carrasco-Queijeiro, Marisa • Heeger, David
Assignees
New York University NYU • US Department of Veterans Affairs
Publication Number
US-9642522-B2
Publication Date
2017-05-09
Expiration Date
2033-03-25
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Abstract
The invention provides methods and kits for detecting, screening, quantifying or localizing the etiology for reduced or impaired cranial nerve function or conduction or associated cranial nucleus or supranuclear input, useful for detecting, diagnosing or screening for increased intracranial pressure, or useful for detecting, diagnosing, monitoring progression of or screening for a disease or condition featuring increased intracranial pressure by tracking eye movement of the subject. The methods may be performed by a) analyzing eye movement of the subject; b) comparing eye movement of the subject to eye movement of a control or the subject's own baseline eye movement; and c) identifying the subject as having eye movement significantly different from the control or the subject's own baseline eye movement.
Core Innovation
The invention provides methods and kits for detecting, screening, quantifying or localizing the etiology of reduced or impaired cranial nerve function or conduction or associated cranial nucleus or supranuclear input by tracking eye movement. This is particularly useful for detecting, diagnosing or screening for increased intracranial pressure, or for diseases or conditions featuring increased intracranial pressure by comparing the subject's eye movement to that of a control or to the subject's own baseline eye movement and identifying significant differences.
Reduced or impaired cranial nerve function may be unilateral or bilateral and caused by increased intracranial pressure or by localized or diffuse lesions or disease processes. The impaired function may result from pathology affecting the nerve itself, its associated nucleus, or supranuclear inputs. The methods analyze eye movement data, often without spatial calibration, by tracking eye movement in response to a visual stimulus, such as a moving video, generating and plotting horizontal and vertical eye position pairs over time to create figures resembling boxes. Deviations from typical box-shaped trajectories indicate dysfunction. Specific patterns in the eye movement data correspond to dysfunction in particular cranial nerves.
The invention addresses limitations of conventional methods for diagnosing elevated intracranial pressure that rely on history, physical exam, imaging or invasive monitoring, which may be insensitive or unpleasant. Automated eye movement tracking at high resolution and without requiring subject calibration enables detection of subtle ocular motility dysfunction associated with elevated intracranial pressure and various neurological diseases. The methods can detect and localize intracranial lesions and monitor disease progression by quantifying changes in ocular motility patterns, providing a noninvasive, sensitive, and quantitative functional assessment of central nervous system integrity.
Claims Coverage
The patent includes two primary independent claims covering methods for detecting reduced or impaired cranial nerve function and for detecting increased intracranial pressure by eye movement tracking and analysis.
Method for detecting or screening reduced or impaired cranial nerve function by eye movement analysis
A method comprising: tracking eye movement of a subject; analyzing this eye movement; comparing the subject's eye movement to that of a control or the subject's own baseline; and identifying the subject as having significantly different eye movement. The cranial nerves involved include II, III, IV, and VI. Eye movement samples of at least about 100,000 positions are obtained in response to a visual stimulus over 30 to 500 seconds. Comparison involves generating and plotting (x,y) pairs representing instantaneous pupil reflection angles over time, forming figures resembling boxes that reflect the trajectory of the visual stimulus. Significant differences are identified using a z-score threshold above 2.
Method for detecting, diagnosing or screening for increased intracranial pressure by eye movement analysis
A method comprising: tracking eye movement of a subject; analyzing this eye movement; comparing the subject's eye movement to that of a control or the subject's own baseline; and identifying the subject as having significantly different eye movement. Eye movement samples of at least about 100,000 positions are obtained in response to a visual stimulus over 30 to 500 seconds. Comparison involves generating and plotting (x,y) pairs as above, yielding box-like trajectory figures. Identifying significant differences uses a z-score threshold above 2.
The independent claims describe novel methods for tracking and analyzing eye movements without spatial calibration to detect impaired cranial nerve function and increased intracranial pressure with high resolution, involving statistical comparison to controls or baselines and visualizing data as box-like trajectories reflecting ocular motility.
Stated Advantages
Provides a noninvasive, low-risk, rapid technique for assessment of elevated intracranial pressure.
Enables detection of subclinical ocular motility dysfunction with high sensitivity.
Reduces the need for CT scans and invasive monitoring techniques in at-risk patients.
Does not require patient spatial calibration or cooperation, enabling use in patients unable to comply with traditional eye-tracking calibration.
Allows quantitative monitoring and localization of intracranial lesions and disease progression.
Facilitates longitudinal tracking of neurological impairment and recovery, applicable in various clinical settings including emergency rooms and outpatient monitoring.
Documented Applications
Detecting, diagnosing or screening for elevated intracranial pressure due to hydrocephalus, brain injury, stroke, mass lesions, or other conditions.
Assessing cranial nerve function, particularly II, III, IV, and VI nerve palsies.
Detection and monitoring of transtentorial herniation as manifested by cranial nerve III palsy.
Detecting, diagnosing or screening for concussion.
Quantifying severity of normal pressure hydrocephalus, detecting shunt malfunction, and optimizing shunt valve pressure.
Evaluating posterior fossa mass effect associated with cranial nerve VI palsy.
Detecting, screening for, or diagnosing disorders that impede conductance through the optic nerve or optic disc, such as optic neuropathy or papilledema.
Use in neurosurgical patients, emergency room screening, concussion assessment for athletes or soldiers, and monitoring neurological disease progression and rehabilitation outcomes.
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