Acute and long-term consequences of exposure to organophosphate nerve agents in humans.

Nerve agents are organophosphate (OP) compounds and among the most powerful poisons known to man. A terrorist attack on civilian or military populations causing mass casualties is a real threat. The OP nerve agents include soman, sarin, cyclosarin, tabun, and VX. The major mechanism of acute toxicity is the irreversible inhibition of acetylcholinesterase. Acetylcholinesterase inhibition results in the accumulation of excessive acetylcholine levels in synapses, leading to progression of toxic signs including hypersecretions, tremors, status epilepticus, respiratory distress, and death. Miosis and rhinorrhea are the most common clinical findings in those individuals acutely exposed to OP nerve agents. Prolonged seizures are responsible for the neuropathology. The brain region that shows the most severe damage is the amygdala, followed by the piriform cortex, hippocampus, cortex, thalamus, and caudate/putamen. Current medical countermeasures are only modestly effective in attenuating the seizures and neuropathology. Anticonvulsants such as benzodiazepines decrease seizure activity and improve outcome, but their efficacy depends upon the administration time after exposure to the nerve agent. Administration of benzodiazepines may increase the risk for seizure recurrence. Recent studies document long-term neurologic and behavior deficits, and technological advances demonstrate structural brain changes on magnetic resonance imaging.

Cervicothoracic epidural hematoma in a toddler with miosis, ptosis, nonspecific symptoms, and no history of major trauma: case report.

INTRODUCTION: Spinal epidural hematomas are uncommon in children. The diagnosis can be elusive as most cases present without a history of trauma, while symptoms can be atypical. CASE REPORT: We encountered a 35-month-old male presenting with nonspecific symptoms and no history of trauma. He later developed unilateral miosis and ptosis; MRI discovered a subacute cervicothoracic epidural which was promptly evacuated. The patient made an excellent recovery. COCLUSIONS: We emphasize the frequent absence of identifiable trauma and the importance of thorough imaging when this entity is suspected. Miosis and ptosis, likely representing a partial Horner syndrome, is an extremely rare presentation, this being one of the only reported cases.

Pin-point pupils with drowsiness as a presentation of Hashimoto's encephalopathy mimicking pontine infarction.

PURPOSE: Hashimoto's encephalopathy (HE) is an autoimmune-mediated encephalopathy with various manifestations. Pupil size change has never been previously reported as a presentation of HE. CASE REPORT: A 65-year-old woman without previous known thyroid disease presented with acute onset of drowsiness and blurred vision. Neurologically, she was drowsy and had bilateral pinpoint-sized pupils without a light reflex, which probably indicated a bilateral pontine lesion. Brain MRI showed two tiny infarctions at the left midbrain and left thalamus, but did not show a pontine lesion, and demonstrated patent vertebral/basilar arteries. Electroencephalography showed intermittent diffuse slowing. She had an elevated protein level (123 mg/dl) in cerebrospinal fluid without pleocytosis. Of note, she had elevated serum levels of anti-TG antibody (282 IU/mL) and anti-TPO antibody (117 IU/mL). Her symptoms improved spontaneously including gradually normalization of her pupil size in 3 days and clear consciousness in 6 days; therefore, corticosteroid was not administered. CONCLUSION: This case illustrates that physicians should be aware of the treatable condition of HE as a possible diagnosis in patients with bilateral pinpoint pupils and drowsiness but without corresponding MRI lesions.

Conjunctival flap in manual sutureless small-incision cataract surgery: a necessity or dogmatic.

To compare the surgical outcomes of manual sutureless small-incision extracapsular cataract surgery (MSICS) with versus without a conjunctival flap for the treatment of cataracts. Prospective, randomized comparison of 220 consecutive patients with visually significant cataracts. Tertiary level eye clinic. 220 consecutive patients with cataracts. Patients assigned randomly to receive either SICS with a conjunctival flap or without one. Operative time, surgical complications, surgically induced astigmatism. Both surgical techniques achieved comparable surgical outcomes with comparable complication rates. The operative time was markedly less in group without flap (mean duration of 7.67 ± 1.45 min) than in group with flap (mean duration of 11.46 ± 1.69 min) (p value <0.001). In the group without a flap intraoperative pupillary miosis was significantly greater (p value 0.039) and on postoperative day 1, there were greater patients with a subconjunctival bleed involving greater than one quadrant of the bulbar conjunctiva (p value <0.0001). Also, post operative conjunctival retraction and consequent wound exposure was also significantly higher in this group (p value 0.026). However, the rate of other serious complications like any postop hyphaema, conjunctival bleb formation, iris prolapse, tunnel stability, shallow anterior chamber, post operative uveitis, malpositioned IOL, retinal detachment, cystoid macular edema, endophthalmitis were comparable in both. Both MSICS with and without a conjunctival flap achieved good surgical outcomes with comparable complication rates. But flapless MSICS is significantly faster. However it may be associated with higher intraoperative miosis and greater postoperative wound exposure.

Ptosis and Miosis Associated with Fibrosing Mediastinitis.

BACKGROUND Fibrosing mediastinitis is a rarely seen, progressive disease. It results from an excessive fibrotic reaction in the mediastinum. We describe a presentation of fibrosing mediastinitis that, to our knowledge, has never been seen before. CASE REPORT A 30-year-old female Colombian flight attendant presented with a right eyelid droop. Examination revealed partial right-sided ptosis and miosis but no anhidrosis. An ill-defined firm swelling was palpable at the root of the neck. Chest radiography revealed a widened mediastinum, and computerized tomography (CT) showed a right paratracheal mass without calcification extending to the thoracic inlet, encasing multiple blood vessels. All basic blood tests, magnetic resonance imaging of the head, and ultrasound Doppler of the neck vessels were normal. History and work up for infections including fungal diseases, granulomatous diseases, vasculitis, and autoimmune diseases were negative. Positron emission tomography (PET) showed significant FDG uptake in the mediastinum. Mediastinal biopsy was histologically consistent with fibrosing mediastinitis. All relevant immunohistochemistry and microbiological studies were negative. Subsequently, the patient developed signs of superior vena cava compression; this was managed by balloon angioplasty, which resulted in improvement of symptoms. However, over time, her symptoms worsened progressively, resulting in a left-sided ptosis and radiological progression of the mass on CT. She received treatment with rituximab and concomitant steroids, which yielded excellent results: the treatment led to both resolution of her symptoms and regression of the mass and its metabolic activity on PET scan. CONCLUSIONS Fibrosing mediastinitis can present with an incomplete Horner's syndrome. Treatment with rituximab and steroids shows promising results in select cases of metabolically active idiopathic fibrosing mediastinitis.

Elevated customary alcohol consumption attenuates opioid effects.

BACKGROUND: Regular alcohol consumption is on the rise among older adults and has the potential of altering the subjective experience of pain and response to pain medications. This study examined the cognitive, analgesic and side effect response to oxycodone in middle age and older adults with elevated levels of customary alcohol consumption in a human laboratory setting. METHODS: After refraining from alcohol for one day, eligible participants underwent baseline assessment cognition and side effects by means of questionnaires that were repeated at three time points (90 min, 5 and 8 h) following administration of a 10 mg oral dose of oxycodone. Response to pain stimulus (Cold Pressor Test (CPT)), pupil size, and plasma oxycodone were also measured. RESULTS: One hundred twenty-eight adults (age 35-85) completed the study day. Compared to those with lower customary alcohol consumption, participants with elevated alcohol consumption showed attenuated opioid-induced pupil constriction and cognitive decline on objective measures of working memory, sustained attention, inhibitory control, coordination on a simulated driving task, and subjective dysphoric effects with enhanced subjective euphoric effects. Oxycodone pharmacokinetics, pain tolerance to CPT, and Berg balance were impacted comparably between alcohol consumption groups. Women endorsed greater negative drug effects, whereas men endorsed positive drug effects. CONCLUSION: Independent of subject's age, elevated customary alcohol consumption attenuates opioid central effects (i.e., pupil miosis, impaired cognition) and gender influences subjective drug effects. Clinicians should consider alcohol consumption and gender when prescribing opioid medications.

[Investigation of acute poisoning event caused by carbofuran].

Objective: To analyze the epidemiological characteristics and response process of an acute poisoning event caused by carbofuran in buttered tea and provide scientific evidence for the investigation of similar events in the future. Methods: Field epidemiological survey, animal experiments and laboratory tests were conducted for an acute poisoning event occurred in Suopo township of Danba county of Sichuan province in 2018. Descriptive epidemiological method was used to analyze the epidemiological characteristics of the acute poisoning event. Results: A total of 26 poisoning cases occurred in 3 villages. The total attack rate was 41.27%. No death cases were reported. The 26 cases occurred in a few minutes after drinking buttered tea, the main symptoms were vomit, dizziness, miosis and nausea. A dog showed the same symptoms after drinking a sample of buttered tea. Carbofuran was detected in buttered tea, vomitus and zanba samples. Conclusions: The acute poisoning was caused by carbofuran in buttered tea, the transmission mode was point source spread. Effective epidemiological investigation and simple animal experiment can provide evidence for the rapid sample detection and clinical treatment of cases in emergency response. Timely case treatment and strict poisoning source control are the key measures to reduce casualty and prevent the spread of poisoning.

Factors influencing pupil behaviour during femtosecond laser assisted cataract surgery.

AIM: Femtosecond laser assisted cataract surgery is associated with pupillary constriction. This study aims to look at patient and surgical factors predisposing to abnormal pupil behaviour during FLACS. METHODS: This prospective observational study included all patients undergoing FLACS in the Princess of Wales Hospital, Bridgend, UK between February and June 2017. Pupils were measured at three time points; immediately before and after laser pre-treatment, and at the start of surgery. Pupil behaviour during surgery was noted in descriptive terms, patient demographic, co-morbidities, eye measurements, suction on time, shifting time and laser energy levels were recorded. RESULTS: Seventy-three eyes were included. Average patient age was 74.84 ±â€¯9.1 years. Mean horizontal pupil sizes immediately before and after femto pre-treatment were 7.87 ±â€¯0.87 mm and 7.7 ±â€¯0.89 mm respectively (P < 0.0005). Mean horizontal pupil size at the start of surgery was 6.83 ±â€¯1.43 mm (P < 0.0005). Short capsulotomy-pupil distance (P = 0.01), shallower anterior chamber (P = 0.0012), smaller pre-operative pupil size (P = 0.045) and longer suction on time (P = 0.0019) were significantly associated with intra-operative miosis during FLACS. Sustained mydriasis was observed in eyes in whom topical diclofenac was used within 2 h of surgery. CONCLUSIONS: FLACS can result in significant pupil miosis. Eyes particularly at risk are ones with smaller pre-operative pupils and shallower anterior chambers and those subjected to longer suction on time. Well-timed NSAIDs application could be protective against this phenomenon.

Spinal Subarachnoid Hemorrhage Induced Intractable Miotic Pupil. A Reminder of Ciliospinal Sympathetic Center Ischemia Based Miosis: An Experimental Study.

AIM: To examine ischemic neurodegeneration of the ciliospinal center on permanent miosis following subarachnoid hemorrhage (SAH). MATERIAL AND METHODS: Nineteen rabbits were examined in this study. The animals were divided into three groups, as control (GI, n=5), sham (GII, n=5) and study group (GIII, n=9). Pupil diameters were measured after giving 0.5 mL physiological saline for sham and autologous arterial blood for the study group into the cervico-thoracic subarachnoid space. After three weeks of follow up, the cervico-thoracic cord and bilateral superior cervical sympathetic ganglia were removed. The pupil diameter values were compared with degenerated neuron volumes of sympathetic ganglia and degenerated neuron densities of thoracic sympathetic nuclei which were studied by stereological methods. RESULTS: The mean pupil diameter was 5180 ± 370 µm and the mean degenerated neuron density of the ciliospinal center was 4 ± 1/mm3 in animals of the control group (GI). These values were 9850 ± 610 εm, 10 ± 3/mm3 in sham (GII), and 7.010 ± 440 εm and 98 ± 21/mm3 in the study (GIII) groups. There was an inverse relationship between degenerated neuron density of the ciliospinal nuclei and pupil diameters. CONCLUSION: We showed and reported for the first time that ciliospinal sympathetic center ischemia-induced neurodegeneration may have been responsible for permanent miosis following SAH.

Efficacy of preoperative nonsteroidal anti-inflammatory drug and the re-dilation technique in minimizing miosis after femtosecond laser in cataract surgery.

PURPOSE: To assess the efficacy of using a nonste-roidal anti-inflammatory drug preoperatively and of applying the re-dilation technique when necessary to minimize pupil size variation when comparing the degree of mydriasis before femtosecond laser pretreatment with that at the beginning of phacoemulsification. METHODS: This retrospective study included patients who underwent cataract surgery using the LenSx (Alcon Laboratories, Inc., Fort Worth, TX). Our routine dilating regimen with flurbiprofen, tropicamide, and phenylephrine was used. The re-dilation technique was applied on eyes that manifested with a pupillary diameter that was smaller than the programmed capsulotomy diameter after laser pretreatment. The technique consists of overcoming pupillary contraction by instilling tropicamide and phenylephrine before phacoemulsification. Pupil size was assessed before femtosecond laser application and at the beginning of phacoemulsification. RESULTS: Seventy-five eyes (70 patients) were included. Nine (12%) eyes underwent the re-dilation technique. There was no significant difference in mean pupillary diameter and mean pupillary area between the two studied surgical time points (p=0.412 and 0.437, respectively). The overall pupillary area constriction was 2.4 mm2. Immediately before opening the wounds for phacoemulsification, none of the eyes presented with a pupillary diameter <5 mm, and 61 (85.3%) eyes had a pupillary diameter >6 mm. CONCLUSION: Preoperative administration of nonsteroidal anti-inflammatory drug and the re-dilation technique resulted in no significant pupil size variation in eyes that were pretreated with the femtosecond laser, when comparing the measurements made before the laser application and at the beginning of phacoemulsification. This approach can avoid the need to proceed with cataract extraction with a constricted pupil.

Benign Raeder syndrome evolving into indomethacin-responsive hemicranial headache.

Benign Raeder syndrome is characterized by a self-limiting unilateral continuous headache associated with ipsilateral ptosis, miosis, and frequently, facial hypohydrosis. Hemicrania continua is a chronic, strictly unilateral continuous headache associated with ipsilateral cranial autonomic symptoms. We report a 50-year-old man who presented with benign Raeder syndrome, which evolved into an indomethacin-responsive hemicranial headache that resembled hemicrania continua.

Reversible chest tube horner syndrome.

A 54-year-old woman who underwent chest tube placement after a lung biopsy was found on the first postoperative day to have ipsilateral ptosis and miosis, suggesting a Horner syndrome. A chest CT scan showed that the tip of the chest tube was apposed to the stellate ganglion. Repositioning of the chest tube later on the first postoperative day led to complete reversal of the Horner syndrome within 24 hours. We propose that the Horner syndrome arose as a result of pressure on the stellate ganglion, which interrupted neural conduction but did not sever the sympathetic pathway ("neurapraxia"). Whether prompt repositioning of the chest tube was critical in reversing the Horner syndrome is uncertain.

[Clinical research of intraoperative floppy iris syndrome during operation].

Intraoperative floppy iris syndrome (IFIS) has been recently identified as a new small pupil syndrome during phacoemulsification. This syndrome is characterized by three intraoperative features: a flaccid iris stroma that undulates and bellows in response to intraocular fluid currents; a propensity for the floppy iris stroma to prolapse toward the tip of phacoemulsification and side-port incisions despite proper wound construction; and progressive intraoperative pupil constriction despite standard preventive preoperative pharmacologic measures designed to prevent this. It is now mostly considered that IFIS is associated with the use of tamsolusin, a highly selective alpha-1A receptor antagonist for the treatment of benign prostatic hypertrophy. It is recommended that a careful history of the use of alpha-1 blocking agents be taken before cataract surgery to anticipate the occurrence of IFIS. A combination of strategies could decrease the complications of IFIS. These procedures include preoperative use of atropine, intracameral injection of dilute phenylephrine or epinephrine, the use of super-cohesive ophthalmic viscosurgical devices, lower phacoemulsification vacuum and aspiration settings and various iris hooks or pupil dilators.

Efficacy of 0.015% intracameral epinephrine for significant miosis induced by photodisruption during femtosecond laser-assisted cataract surgery.

Despite the various advantages of femtosecond laser-assisted cataract surgery (FLACS), pupillary constriction during laser photodisruption is considered one of the most unfavorable events. This study aimed to investigate the efficacy of intracameral 0.015% epinephrine injection for miosis after laser pretreatment during FLACS.A total of 82 patients who underwent FLACS for age-related cataracts were investigated in this retrospective study. The epinephrine group included patients who received intracameral epinephrine injection for miosis after femtosecond laser pretreatment, while the no-epinephrine group included the patients who underwent FLACS without intracameral epinephrine due to minimal miosis. Quantitative pupil area measurements were performed through the analysis of captured images extracted from surgical videos of both femtosecond laser pretreatment and phacoemulsification.Laser photodisruption induced miosis in both groups, although the degree of miosis was greater in the epinephrine group (4.65 ±â€Š0.87 mm) than in the no-epinephrine group (6.30 ±â€Š0.65 mm; P < .001). The intracameral epinephrine injection significantly increased the pupil diameter from 4.65 ±â€Š0.87 to 5.49 ±â€Š0.76 mm (21.61 ±â€Š22.68%; P < .001) and the pupil area from 70.28 ±â€Š24.46 to 96.49 ±â€Š25.24 mm (52.89 ±â€Š63.54%; P < .001). After additional viscomydriasis, there was no difference between groups in pupil diameter (epinephrine vs no-epinephrine group; 6.10 ±â€Š0.77 vs 6.39 ±â€Š0.65 mm; P = .073).A single intracameral injection of 0.015% epinephrine provided immediate and appropriate redilation of pupil in patients with significant miosis after femtosecond laser photodisruption. Intracameral epinephrine is a simple and practical option for pupil redilation in case of miosis during FLACS.

Arousal and the pupil: why diazepam-induced sedation is not accompanied by miosis.

RATIONALE: There is a close relationship between arousal and pupil diameter, decrease in the level of arousal being accompanied by constriction of the pupil (miosis), probably reflecting the attenuation of sympathetic outflow as sedation sets in. Paradoxically, sedation induced by benzodiazepines is not accompanied by miosis. OBJECTIVE: The objective of this study was to examine the hypothesis that diazepam may attenuate both the sympathetic and the opposing parasympathetic outflow to the iris, which may mask the miosis. Dapiprazole (sympatholytic) and tropicamide (parasympatholytic) were applied topically, together with the cold pressor test (CPT), to manipulate the sympathetic/parasympathetic balance. MATERIALS AND METHODS: Sixteen healthy male volunteers participated in four weekly sessions according to a balanced double-blind protocol. Diazepam 10 mg (two sessions) and placebo (two sessions), associated with either 0.01% tropicamide or 0.5% dapiprazole eyedrops, were administered orally. Pupil diameter, light and darkness reflexes and pupillary sleepiness waves were recorded with infrared video pupillometry, alertness was measured by critical flicker fusion frequency (CFFF) and visual analogue scales (VAS), blood pressure and heart rate by conventional methods. CPT was applied after post-treatment testing. Data were analysed by analysis of variance, with multiple comparisons. RESULTS: Diazepam caused sedation (reduction in VAS alertness scores and CFFF, increase in sleepiness waves), dapiprazole had a sympatholytic and tropicamide a parasympatholytic effect on the pupil. Diazepam had no effect on pupil diameter and reflexes or their modifications by the antagonists. CPT increased pupil diameter, blood pressure and heart rate, and the increase only in systolic blood pressure was attenuated by diazepam. CONCLUSIONS: Diazepam-induced sedation is not accompanied by any change in either the sympathetic or parasympathetic influence on the iris.

Phenylephrine and pilocarpine eye drop test for dementia with Lewy bodies and Alzheimer's disease.

Pupillary response test using dilute phenylephrine, a sympathetic agonist, and dilute pilocarpine, a cholinergic agonist, were performed in 24 patients with dementia with Lewy bodies (DLB), 40 patients with Alzheimer's disease (AD), and 23 normal elderly subjects. The mydriatic response to 0.5% phenylephrine was significantly greater in the DLB group than in the AD and control groups. The mydriatic change correlated inversely with the reduction in cardiac 123I-metaiodobenzylguanidine uptake. In contrast, miotic response to 0.0625% pilocarpine was significantly greater in the DLB and AD groups than in the control group. The pupil assay using combined phenylephrine and pilocarpine eye drop test may be useful in the detection of patients with DLB and AD and in distinguishing between them.

Spasm of the near reflex in a patient with multiple sclerosis.

A 33-year-old woman with a history of relapsing-remitting multiple sclerosis presented with complaints of episodic horizontal diplopia and blurred vision over the past two months. The patient gave a past history of similar episodes of diplopia that had occurred with previous clinical relapses of her multiple sclerosis. On eye movement examination, the patient exhibited intermittent spasms of convergence coupled with miosis. On upward gaze, the convergence and miosis became more marked. An auto-refraction revealed variable measurements in both eyes, consistent with accommodative spasms. A cycloplegic auto-refraction revealed significantly lower myopia present in both eyes than the initial pre-cycloplegic auto-refraction with minimal variability in readings. Symptomatic relief was achieved by cycloplegia and spectacle correction.

The pupillary response in traumatic brain injury: a guide for trauma nurses.

Trarumatic brain injuries (TBIs) affect more than 1.4 million Americans annually. Trauma nurses caring for these patients routinely perform serial neurologic assessments, including pupillary examinations. While trauma nurses are likely familiar with basic components of the pupillary examination, some confusion about more specific aspects of the examination and the physiologic basis of the pupillary response may still remain, particularly as it pertains to patients with TBI. Therefore, the purpose of this article is to identify the key components of a pupillary examination and its associated physiologic response. A case study is provided to illustrate the application of this information among patients with TBI.

Choroideremia: melanopsin-mediated postillumination pupil relaxation is abnormally slow.

PURPOSE: To investigate the rod-cone and melanopsin pupillary light response (PLR) pathways in choroideremia. METHODS: Eight patients with choroideremia and 18 healthy age-matched controls underwent chromatic pupillometry by applying blue (463 nm) and red light (643 nm) at 100 lux intensity to the right eye while recording pupil diameters. Absolute baseline pupil size (mm), normalized maximal pupil constriction and the early and late postillumination pupillary dilation, from 0 to 10 seconds and 10 to 30 seconds after the end of illumination, respectively, were determined. Postillumination responses to blue light were considered to be primarily driven by melanopsin activation of the intrinsic photosensitive retinal ganglion cells. RESULTS: Baseline pupil diameters were comparable in patients with choroideremia and control subjects (p = 0.48). The maximum pupil constriction in patients with choroideremia was severely weakened in red light but only mildly weakened in blue light (p < 0.05). Postillumination dilation of the pupil was normal after red illumination but extremely protracted after blue illumination. Also, in contrast to healthy subjects, no abrupt change in the dilation curve was seen in the patients after the end of blue illumination, the early-phase dilation being completely abolished (p < 0.01). CONCLUSION: Rod-cone-driven pupil responses were decreased as expected in an outer retinal degeneration, and near-normal pupil constriction in blue light supports that the melanopsin system is normal. In contrast, the lack of brisk early-phase dilation after blue illumination in choroideremia is remarkable and may be interpreted to mean that the absence of photoreceptor inhibition promotes a tonic contraction of the pupil.