Anisocoria and Poor Pupil Reactivity by Quantitative Pupillometry in Patients With Intracranial Pathology.

OBJECTIVES: To describe the prevalence and associated risk factors of new onset anisocoria (new pupil size difference of at least 1 mm) and its subtypes: new onset anisocoria accompanied by abnormal and normal pupil reactivities in patients with acute neurologic injuries. DESIGN: We tested the association of patients who experienced new onset anisocoria subtypes with degree of midline shift using linear regression. We further explored differences between quantitative pupil characteristics associated with first-time new onset anisocoria and nonnew onset anisocoria at preceding observations using mixed effects logistic regression, adjusting for possible confounders. SETTING: All quantitative pupil observations were collected at two neuro-ICUs by nursing staff as standard of care. PATIENTS: We conducted a retrospective two-center study of adult patients with intracranial pathology in the ICU with at least a 24-hour stay and three or more quantitative pupil measurements between 2016 and 2018. MEASUREMENTS AND MAIN RESULTS: We studied 221 patients (mean age 58, 41% women). Sixty-three percent experienced new onset anisocoria. New onset anisocoria accompanied by objective evidence of abnormal pupil reactivity occurring at any point during hospitalization was significantly associated with maximum midline shift (ß = 2.27 per mm; p = 0.01). The occurrence of new onset anisocoria accompanied by objective evidence of normal pupil reactivity was inversely associated with death (odds ratio, 0.34; 95% CI, 0.16-0.71; p = 0.01) in adjusted analyses. Subclinical continuous pupil size difference distinguished first-time new onset anisocoria from nonnew onset anisocoria in up to four preceding pupil observations (or up to 8 hr prior). Minimum pupil reactivity between eyes also distinguished new onset anisocoria accompanied by objective evidence of abnormal pupil reactivity from new onset anisocoria accompanied by objective evidence of normal pupil reactivity prior to first-time new onset anisocoria occurrence. CONCLUSIONS: New onset anisocoria occurs in over 60% of patients with neurologic emergencies. Pupil reactivity may be an important distinguishing characteristic of clinically relevant new onset anisocoria phenotypes. New onset anisocoria accompanied by objective evidence of abnormal pupil reactivity was associated with midline shift, and new onset anisocoria accompanied by objective evidence of normal pupil reactivity had an inverse relationship with death. Distinct quantitative pupil characteristics precede new onset anisocoria occurrence and may allow for earlier prediction of neurologic decline. Further work is needed to determine whether quantitative pupillometry sensitively/specifically predicts clinically relevant anisocoria, enabling possible earlier treatments.

Comparison of out of hospital cardiac arrest due to acute brain injury vs other causes.

BACKGROUND: Acute brain injury (ABI) can cause out of hospital cardiac arrest (OHCA). The aim of this study was to compare clinical features, mortality and potential for organ donation in patients with OHCA due to ABI vs other causes. METHODS: From January 2017 to December 2018, all adult patients presenting to ED for OHCA were considered for the study. Two physicians established the definitive cause of OHCA, according to clinical, laboratory, diagnostic imaging and autoptic findings. Clinical features in patients with OHCA due to ABI or other causes were compared. RESULTS: 280 patients were included in the analysis. ABI was the third most frequent cause of OHCA (21, 7.5%); ABIs were 8 subarachnoid hemorrhage, 8 intracerebral hemorrhage, 2 ischemic stroke, 2 traumatic spinal cord injury and 1 status epilepticus respectively. Neurological prodromes such as seizure, headache and focal neurological signs were significantly more frequent in patients with OHCA due to ABI (OR 5.34, p = 0.03; OR 12.90, p = 0.02; and OR 66.53, p < 0.01 respectively) while among non-neurological prodromes chest pain and dyspnea were significantly more frequent in patients with OHCA due to other causes (OR 14.5, p < 0.01; and OR 10.4, p = 0.02 respectively). Anisocoria was present in 19% of patients with OHCA due to ABI vs 2.7% due to other causes (OR 8.47, p < 0.01). In 90.5% of patients with ABI and in 53.1% of patients with other causes the first cardiac rhythm was non shockable (OR 8.1; p = 0.05). Multivariate logistic regression analysis revealed that older age, active smoking, post-traumatic OHCA, neurological prodromes, anisocoria at pupillary examination were independently associated with OHCA due to ABI. Patients with ABI showed a higher mortality compared with the other causes group (19 pts., 90.5% versus 167 pts., 64.5%; p = 0.015). Potential organ donors were more frequent among ABI than other causes group (10 pts., 47.6% vs 75 pts., 28.9%) however the difference did not reach the statistical significance (p = 0.07). CONCLUSIONS: ABI is the third cause of OHCA. Neurological prodromes, absence of chest pain and dyspnea before cardiac arrest, anisocoria and initial non-shockable rhythm might suggest a neurological etiology of the cardiac arrest. Patients with OHCA due to ABI has an unfavorable outcome, however, they could be candidate to organ donation.

The Prevalence of Physiological Anisocoria and its Clinical Significance - A Neurosurgical Perspective.

AIM: We aimed to estimate the prevalence of physiological anisocoria and also evaluate the accuracy of clinical assessment of anisocoria employed in routine bedside examination. MATERIALS AND METHODS: A total of 708 voluntary subjects between the ages of 20-69 years who had no history of ophthalmologic or neurological disease other than refractive error were included in the study. In a closed room with uniform ambient lighting, the subjects' pupils were examined clinically and the presence or absence of anisocoria was recorded. This was followed by photography of the subjects' pupils using a digital camera secured on a tripod at a fixed distance from the subject's face. A difference in pupillary size of 0.4 mm or more was considered anisocoria. RESULTS: Of the 708 subjects, 361 (51%) were males. The average pupillary diameter of the subjects was 4.99 mm. Ninety-seven (13.7%) had measured anisocoria on photography. Ninety-seven subjects (13.7%) also had anisocoria on clinical examination, however, only 45 of them had measured anisocoria. The clinical measurement of anisocoria, therefore, showed a specificity of 0.91 and a sensitivity of 0.46. With a prevalence of anisocoria of 13.7%, the positive predictive value was 0.46, and the negative predictive value was 0.91. CONCLUSIONS: The prevalence of physiological anisocoria was 13.7%, which is less than what has previously been reported. The sensitivity of clinical examination in detecting early anisocoria is poor. Patients at risk of developing uncal herniation may, therefore, benefit from routine bedside pupillary assessment with a portable device such as a pupillometer.

Pupil size and anisocoria in children measured by the plusoptiX photoscreener.

PURPOSE: To investigate pupil size and the incidence of anisocoria in children at a single community-based practice using the plusoptiX A04 and A09 photoscreeners (plusoptiX GmbH, Nuremberg, Germany). METHODS: The medical records of consecutive patients <1 to 17 years of age who had received a comprehensive ophthalmological examination that included photoscreening with the plusoptiX were retrospectively reviewed. Data collected included sizes of both pupils, age, sex, laterality, and magnitude of anisocoria. RESULTS: A total of 1,306 patient records were reviewed. Of these, 1,057 (80.9%) had 0-0.4 mm of anisocoria; 219 (16.8%), 0.5-0.9 mm; 20 (1.5%), 1.0-1.4 mm; and 10 (0.8%), ≥1.5 mm. Magnitude of anisocoria appears to increase with age (P = 0.0073). Pupil size and age were positively correlated (P < 0.0001), that is, older children had larger pupils. Average pupil size of children <1 year of age was 5.0 mm; of children ≥16 years of age, 6.1 mm. When sorted into age buckets of 0-3, 4-7, 8-11, 12-15, and 16-17, this increase becomes apparent. There is no significant relationship between pupil size and sex (P = 0.14). CONCLUSIONS: Our study of 1,306 children shows that pupil size increases through childhood, and that 19.1% of children in a clinical population have anisocoria >0.4 mm.

Incidence of pupillary involvement, course of anisocoria and ophthalmoplegia in diabetic oculomotor nerve palsy.

AIMS: To derive a reliable estimate of the frequency of pupillary involvement and to study the patterns and course of anisocoria in conjunction with ophthalmoplegia in diabetes-associated oculomotor nerve palsy. MATERIALS AND METHODS: In this prospective analytical study, standardized enrolment criteria were employed to identify 35 consecutive patients with diabetes-associated oculomotor nerve palsy who were subjected to a comprehensive ocular examination. Standardized methods were used to evaluate pupil size, shape, and reflexes. The degree of anisocoria, if present and the degree of ophthalmoplegia was recorded at each visit. RESULTS: Pupillary involvement was found to be present in 25.7% of the total number of subjects with diabetic oculomotor nerve palsy. The measure of anisocoria was < 2 mm, and pupil was variably reactive at least to some extent in all cases with pupillary involvement. Majority of patients in both the pupil-involved and pupil-spared group showed a regressive pattern of ophthalmoplegia. Ophthalmoplegia reversed much earlier and more significantly when compared to anisocoria. CONCLUSIONS: Pupillary involvement in diabetes-associated oculomotor nerve palsy occurs in about 1/4 th of all cases. Certain characteristics of the pupil help us to differentiate an ischemic insult from an aneurysmal injury to the 3 rd nerve. Ophthalmoplegia resolves much earlier than anisocoria in diabetic oculomotor nerve palsies.

Anisocoria cotidiana: epidemiología de la anisocoria en un centro de nivel secundario / Everyday anisocoria: anisocoria epidemiology in a secondary care setting

Objetivo: Determinar la importancia relativa de las distintas formas de anisocoria en un centro sanitario de nivel secundario. Métodos: Estudio prospectivo longitudinal, incluyendo todos los pacientes remitidos por este motivo a la consulta de Neuroftalmología del Hospital Universitario del Henares, Madrid, España, desde noviembre de 2008 hasta octubre de 2011. Se estudiaron las diferencias en el diámetro pupilar en condiciones de alta y baja luminosidad. Los pacientes fueron sometidos a una exploración oftalmológica completa, y a las pruebas de apraclonidina, cocaína, pilocarpina 0,125% y pilocarpina 2% en caso de considerarse necesario. Resultados: Treinta y dos casos de anisocoria fueron referidos durante estos 3 años. No se encontró asociación con la edad ni el sexo. Los diagnósticos fueron: pupila de Adie, 4 casos; síndrome de Horner, 5 casos; midriasis unilateral episódica benigna, 3 casos; causas locales, 4 casos; anisocoria fisiológica, 5 casos. A pesar de una completa historia clínica y exploración, la causa de la anisocoria no se pudo determinar en 11 casos. En 4 de estos casos el paciente padecía migrañas y en otros 4 consumía psicofármacos. En 3 casos ambos factores de riesgo estaban presentes. En un caso la anisocoria fue la pista inicial que llevó al diagnóstico de un paraganglioma cervical. Conclusiones: La anisocoria es un signo clínico que no traduce habitualmente enfermedad grave. Con nuestros protocolos, un número alto de los casos de anisocoria queda sin filiar. La migraña y los psicofármacos podrían estar asociados a estas formas de anisocoria(AU)

Objetive: To determine the relative importance of the different forms of anisocoria in a General Hospital. Methods: A prospective, longitudinal study was conducted including all patients referred for this reason to the Neuro-Ophthalmology Unit of the Henares University Hospital, Madrid (Spain), from November 2008 to October 2011. The differences in pupil diameter were studied under high and low luminosity. The patients were given a full ophthalmological examination, as well as performing the apraclonidine, cocaine, pilocarpine 0.125% and pilocarpine 2% tests, if they were considered necessary. Results: Thirty-two cases of anisocoria were referred during the three years of the study. No relationship was found with age or gender. The diagnostic results were: Adie's pupil, 4 cases; Horner syndrome, 5 cases; benign episodic unilateral mydriasis, 3 cases; local causes, 4 cases; physiological anisocoria, 5 cases. Despite a full clinical history and examination, the cause of the anisocoria could not be determined in 11 cases. In 4 of these cases, the patient suffered from migraines and in another 4 psychotropic drugs were taken. Both risk factors were present in 3 cases. In one case the anisocoria was the initial clue that led to the diagnosis of a cervical paraganglioma. Conclusions: Anisocoria is a clinical sign that does not usually signify a serious disease. With our protocols, a high number of anisocoria cases are still of unknown origin. Migraines and psychotropic drugs could be linked to these forms of anisocoria(AU)

[Everyday anisocoria: anisocoria epidemiology in a secondary care setting]. / Anisocoria cotidiana: epidemiología de la anisocoria en un centro de nivel secundario.

OBJECTIVE: [corrected] To determine the relative importance of the different forms of anisocoria in a General Hospital. METHODS: A prospective, longitudinal study was conducted including all patients referred for this reason to the Neuro-Ophthalmology Unit of the Henares University Hospital, Madrid (Spain), from November 2008 to October 2011. The differences in pupil diameter were studied under high and low luminosity. The patients were given a full ophthalmological examination, as well as performing the apraclonidine, cocaine, pilocarpine 0.125% and pilocarpine 2% tests, if they were considered necessary. RESULTS: Thirty-two cases of anisocoria were referred during the three years of the study. No relationship was found with age or gender. The diagnostic results were: Adie's pupil, 4 cases; Horner syndrome, 5 cases; benign episodic unilateral mydriasis, 3 cases; local causes, 4 cases; physiological anisocoria, 5 cases. Despite a full clinical history and examination, the cause of the anisocoria could not be determined in 11 cases. In 4 of these cases, the patient suffered from migraines and in another 4 psychotropic drugs were taken. Both risk factors were present in 3 cases. In one case the anisocoria was the initial clue that led to the diagnosis of a cervical paraganglioma. CONCLUSIONS: Anisocoria is a clinical sign that does not usually signify a serious disease. With our protocols, a high number of anisocoria cases are still of unknown origin. Migraines and psychotropic drugs could be linked to these forms of anisocoria.

Distribution of photopic pupil diameter in the Tehran eye study.

PURPOSE: To determine the photopic pupil diameter and its determinants in a sample derived from a population-based survey in Tehran. METHODS: In a cross-sectional study with a stratified random cluster sampling approach, 410 people age 14 years and over were selected from those residing in the first four municipality districts of Tehran after applying exclusion criteria, and 800 eyes (399 right eyes and 401 left eyes) were examined with the Orbscan II. The main outcome measure was the mean pupil diameter under photopic conditions, and possible correlations with potential determinants were evaluated through linear regression analyses. The design effect of a cluster sampling approach was observed and adjusted for. RESULTS: The mean age of the participants was 40.6 +/- 16.8 years and 38.8% were male. The mean photopic pupil diameter (PPD) was 3.70 mm (range 2.30 to 5.10; 95% confidence interval (CI) 3.62 to 3.78). The mean PPD was 3.67 mm (95% CI, 3.54 to 3.81) in men and 3.72 mm (95% CI, 3.63 to 3.81) in women (p = 0.481). There was a significant reduction of 0.021 mm in PPD per year of aging (r = -0.49, p < 0.001). There was also a significant inverse correlation between PPD and spherical equivalent (r = -0.12, p = 0.034), while there was 0.66-mm increase in PPD with every 1.0-mm increase in the anterior chamber depth (ACD) (p < 0.001). Anisocoria, defined as a pupil diameter difference more than 0.4 mm between two eyes, was observed in 12.2% of the study population. CONCLUSION: While the mean PPD measured with the Orbscan II was 3.70 mm in a sample derived from a population-based survey in Tehran, the scarcity of similar studies and reports concerning the pupil diameter measured with the Orbscan II makes it difficult to draw eligible comparisons. The pupil diameter has reverse correlations with age and spherical equivalent, a direct correlation with ACD, but is not correlated with gender.

Bilateral tonic pupils: Holmes Adie syndrome or generalised neuropathy?

AIM: To compare the pupil signs in patients with bilateral pupillotonia caused by Holmes-Adie syndrome or generalised peripheral neuropathy. METHODS: Infrared video pupillographic techniques were used to measure a number of pupil variables in patients with Holmes-Adie syndrome, generalised neuropathy (various aetiologies) and healthy age-matched control subjects. RESULTS: Regardless of aetiology, the patients generally had pupil signs typical of pupillotonia (small dark diameters, large light diameters, tonic near responses, attenuated light responses with light-near dissociation, and sector palsy). However, significant differences were found in the prevalence and magnitude of several pupil variables in the two patient groups. In particular, sector palsy and anisocoria exceeding 1 mm (in the light) were seen much more commonly in Holmes-Adie patients than patients with generalised neuropathy. The presence of both these pupil signs can be used to distinguish between these diagnoses with a sensitivity of 58% and a specificity of 90%. CONCLUSIONS: The tonic pupils of patients with Holmes-Adie syndrome are significantly different to those found in patients with generalised neuropathy; recognition of these differences may allow distinction between these diagnoses.

Alteraçöes oculares na doença de Chagas crônica: comprovaçäo na regiäo endêmica de Agua Comprida (MG) / Ocular alterations in chronic Chaga's disease: evidence at endemic Agua Comprida (MG) region

Objetivo: Comprovar na regiäo endêmica de Agua Comprida (MG) a maior incidência de anisocoria e menor pressäo intra-ocular (Po) em chagásicos anteriormente observados em outra regiäo endêmica da doença de Chagas (Mambaí, GO). Material e métodos: Em estudo prospectivo, mascarado e pareado quanto a idade, sexo e cor, foram analisados 190 pacientes (95 pares de chagásicos e näo-chagásicos). Em 84 pares, realizou-se estudo fotográfico da pupila para a determinaçäo do diâmetro pupilar e frequências de anisocoria (diferença>0,3 mm). Em 95 pares, foi estudada a pressäo intra-ocular entre chagásicos e näo-chagásicos. Resultados: No grupo chagásicos foram observados 25 casos de anisocoria (29,8 por cento) e nos näo-chagásicos, 10 ocorrências (11,9 por cento), diferença essa estatisticamente significante (p = 0,007). Näo houve diferenças estatisticamente significantes para o diâmetro pupilar entre os grupos tanto para OD quanto para OE. Os chagásicos mostraram uma Po média de 11,3 + ou - 2,5 mmHg em OD e de 11,3 + ou - 2,4 mmHg em OE e os näo chagásicos uma Po de 13,1 + ou - 2,6 e 13,1 + ou - 2,5 mmHg respectivamente, diferenças essas estatisticamente significantes entre chagásicos e näo-chagásicos tanto para OD quanto para OE (pOD=pOE<0,0001). Tais diferenças mantiveram-se quando a Po foi comparada quanto ao sexo (feminino p=0,002, masculino p=0,003). Conclusäo: Os resultados comprovam a maior frequência de anisocoria e menores valores de pressäo intra-ocular em pacientes portadores da forma crônica da doença de Chagas.

Effect of light on the prevalence of simple anisocoria.

PURPOSE: Because simple anisocoria is believed to decrease in bright light, the authors determined the prevalence of simple anisocoria under different lighting conditions. METHODS: The authors measured the pupil size of 104 healthy subjects with infrared videography at four clinically accessible light levels: darkness; darkness with a hand-held light shining from below; room light; and room light with the hand light shining from below. RESULTS: Of the 104 subjects, 40 (38%) were men and 64 (62%) were women. The ages ranged from 12 to 71 years (mean, 36.3 +/- 12.5 years). The mean decrease in pupillary diameter from darkness to the brightest condition was 1.89 mm. Based on the traditional definition of a pupillary diameter difference of 0.4 mm or greater, the prevalence of simple anisocoria decreased from 18% in darkness to 8% in room light with the hand-held light shining from below. The prevalence of anisocoria varied considerably when other definitions were used. Repeated measures analysis of variance showed that pupillary area difference decreased with brighter conditions (P = 0.026). However, the ratio of the pupillary areas did not change with brighter conditions (P = 0.666). CONCLUSIONS: The prevalence of simple anisocoria decreases with brighter conditions based on pupillary diameter difference. However, this decrease is not apparent when anisocoria is expressed as pupillary area ratio. Those clinicians who measure pupils will find that simple anisocoria decreases in bright light. However, with gross observation where perception of an anisocoria may be related more to the ratio of the pupillary areas, simple anisocoria may not seem to change much with brighter conditions.

Anisocoria na fase crônica da doença de chagas / Anisocoria in the chronic phase of Chagas' disease

Para verificar a freqüência de anisocoria em portadores da fase crônica da doença de Chagas foi feito estudo prospectivo e duplo cego. Foram submetidos a exame oftalmológico 131 pacientes com sorologia positiva para doença de Chagas e 138 indivíduos com sorologia negativa, da populaçao do município de Mambaí (GO), regiao endêmica de doença de Chagas. Para a avaliaçao da presença ou nao de anisocoria foi realizada a pupilometria com régua. Observamos a presença de anisocoria em 10(7,6 por cento) pacientes chagásicos e em 3(2,1 por cento) controles. O teste do qui-quadrado revelou que as diferenças detectadas foram estatisticamente significantes ao nível de 5 por cento. A doença de Chagas deve ser incluída entre as causas de anisocoria.

[Anisocoria in the chronic phase of Chagas' disease]. / Anisocoria na fase crônica da doença de Chagas.

To compare the frequency of anisocoria in patients with chronic Chagas' disease a prospective double-blind study was done in 131 patients with positive serology for Chagas' disease and 138 negative, at Mambaí (GO-Brazil), which is an endemic area for Chagas' disease. To detect anisocoria, pupillometry was done with a millimetric ruler. Anisocoria was seen in 10(7.6%) patients with Chagas' disease and in 3(2.1%) normal subjects. The chi-square test showed statistical significance at level of 5%. Chagas' disease must be included among the causes of anisocoria.

Normal pupil size and anisocoria in newborn infants.

The incidence of anisocoria in the newborn period is not well described. Additionally, the normal range of infant pupil size is not well defined. Eight-eight healthy newborns were evaluated. Pupil size and color were obtained from photographs. The mean (+/- SD) pupil size was 3.8 +/- 0.8 mm. There was no statistical difference between right and left eyes. A statistically significant difference in pupil size was found between blue and brown eyes. The incidence of anisocoria was found to be 21%. No difference was greater than 1.0 mm. The incidence of anisocoria was no different on the basis of eye color.