Fixed and dilated pupils (FDPs) have become synonymous with devastating neurological damage and brainstem injury commonly associated with mass effect and herniation. Infrequently, changes in pupillary light response have been described with seizures; however, the loss of pupillary response with documented Neurological Pupil index has not been well established in patients with seizures.
We present a case report describing a middle-aged female patient with focal status epilepticus with intermittent FDPs. An abnormal pupillary response occurred with right hemispheric lateralized periodic discharges and resolution with anti-seizure medication escalation. To our knowledge, this is the first description of objective documentation of reversible FDP as a possible clinical correlate of lateralized periodic discharges.
The use of handheld automated pupillometry in conjunction with electroencephalogram (EEG) has provided the therapeutic direction. Further research is warranted to fully describe the mechanistic underpinnings of these observations.
Pupillary size and light response are valuable components of neurological examination, especially in the care of critically ill patients when pupillary size and reactivity to light may provide an objective finding of neurological changes. Abnormal pupillary response to light, based on reactivity or pupil size and asymmetry, can be seen in a variety of conditions, ranging from benign or congenital conditions to a life-threating intracranial process [
A right-handed female patient in her late 50s with human immunodeficiency virus (HIV) complicated by recurrent cryptococcal meningitis and seizures was admitted to the neurosciences critical care unit after presenting with bilateral tonic-clonic seizure evolving into focal motor status epilepticus with impaired awareness and left-hand twitching. The patient was compliant with her home regimen of levetiracetam and antiretroviral therapy for HIV. On arrival, she was afebrile, hemodynamically stable, unable to follow instructions, and had notable left-sided hemiparesis.
She was initially treated with lorazepam and lacosamide with resolution of movements; however, persistent tactile stimulation was required to maintain arousal. Ultimately, the patient was intubated to protect the airway. cEEG was started and showed focal slowing over the right parietotemporal region, without clinical events. Over the course of several days, the patient exhibited intermittent left forehead, cheek, and thumb twitching. On cEEG, these movements corresponded with right hemispheric lateralized rhythmic delta activity with sharp waves at 1.5–2 Hz with frequent evolution into well-formed seizures, meeting the criteria for electroclinical status epilepticus (occupying >20% of a 60-minute EEG period) [
Brain magnetic resonance imaging showed cortical restricted diffusion in the right parietal, temporal, and occipital lobes, as well as bilateral temporal lobe encephaloceles with associated encephalomalacia without evidence of a midbrain lesion or effacement of the peri-mesencephalic cisterns. Two lumbar punctures were performed over the course of 1 week given her history of recurrent cryptococcal infections and potential elevated intracranial pressure (ICP) driving her focal seizure activity. The cerebrospinal fluid had a white blood cell count of <3 cells/μL, an red blood cell count of <1 cell/µL, glucose levels of 53 and 79 mg/dL, and protein levels of 23 and 28 mg/dL. The opening pressure was 18 cmH2O.
On hospital day 9, the patient had new FDPs documented by NPi using a NeurOptics NPi-200 pupillometer (Neuroptics Inc., Irvine, CA, USA). Computed tomography (CT) head imaging showed no signs of herniation, and CT perfusion was most consistent with hyper-perfusion in the right temporal and occipital lobes concerning focal status epilepticus (
Without imaging evidence of ICP increase or mass effect, management was focused on the treatment of focal status epilepticus rather than cerebral herniation. The patient’s pupils were reactive following the administration of a midazolam bolus. Anesthetics were escalated to achieve burst suppression EEG along with escalating anti-seizure medications. She exhibited an abnormal pupillary light response 12 additional times over 4 days (
The patient displayed FDP on pupillometry, which coincided with the clinical and electrographic occurrence of focal motor status epilepticus and without evidence of third nerve compression in relation to cerebral herniation syndrome. Conversely, FDP using pupillometry resolved the anesthetic escalation and resolution of the right LPDs. Together, these observations suggest a direct relationship between FDP and focal seizures.
Pupil alterations during seizures were described as early as 1881 by Sir William Richard Gowers [
Several case reports have discussed lateralization of unilateral mydriasis during several seizure types, termed ictal mydriasis, which is most often focal and associated with conjugate gaze deviation [
Automated pupillometry is a noninvasive, portable diagnostic technique that provides a standardized quantitative assessment of the patient’s pupils and their pupillary light reflex. These devices generate a standardized light stimulus using an infrared light-emitting diode and capture pupil images before, during, and after the stimulus. These images are then immediately processed to obtain a series of standardized and metric data. Proprietary device-specific metrics include the commonly used and studied NPi, ranging from 0 to 5, with 0 being nonreactive, 5 being fully reactive, and NPi of <3 generally considered to be less than the normal limits.
Changes in pupil size, shape, and light reflex are traditionally interpreted as markers of elevated ICP and cerebral herniation [
In our patient, EEG showed LPDs with sharp wave morphology over the right parietotemporal region, occurring 0.7–1.0 Hz in FDP (
Our study, as a single case within our academic neurosciences critical care unit, has limited generalizability but presents direct and quantified evidence for the association. However, this observation requires further validation in a cohort of patients.
To our knowledge, this is the first description of objective documentation of symmetric FDP by pupillometry as a manifestation of LPDs in a critically ill patient with return of the pupillary light reflex after management with anti-seizure medications. FDPs may be a clinical manifestation of LPDs. The use of handheld automated pupillometry within the neurocritical care unit, in conjunction with cEEG, provided the therapeutic direction. Further research is warranted to fully describe the mechanistic underpinnings of these observations.
Approval for this study was waived in accordance with policies of our institution because this study did not include protected health information, data analysis, or testing of a hypothesis, and was de-identified. The requirement for informed consent was waived.
No potential conflict of interest relevant to this article.
Conceptualization: CTP, RGG. Data curation: all authors. Methodology: all authors. Project administration: all authors. Visualization: CTP, KSH. Writing–original draft: all authors. Writing–review & editing: all authors.
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Neurological pupil index
Computed tomography perfusion imaging. (A) Mean transit time (MTT), (B) cerebral blood flow (CBF), (C) cerebral blood volume (CBV), consistent with hyper-perfusion in the right temporal and occipital lobes (arrows).
Screenshot of a 10-second clip of an electroencephalogram in bipolar montage displaying, (A) continuous right hemispheric lateralized periodic discharges with sharp wave morphology, occurring at approximately 0.7–0.8 Hz, noted by an arrow and asterisk, coinciding with fixed and dilated pupil (FDP). (B) Ten-second clip of an electroencephalogram following the administration of a 5-mg midazolam bolus with appearing transient improvement of lateralized periodic discharges and resolution of FDP.