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The spectrum of autoimmune autonomic neuropathies.

We analyzed the clinical characteristics of 18 patients (13 female, 5 male) who had autoimmune autonomic neuropathy (AAN) and ganglionic acetylcholine receptor (AChR) autoantibodies. Mean age was 61.4 years (standard deviation, 12.0 years). Ten patients had subacute symptom onset, six with an antecedent event. Eight patients had chronic AAN, characterized by insidious symptom onset, without antecedent event, and gradual progression. A majority of patients with high antibody values (>1.00 nmol/L) had a combination of sicca complex (marked dry eyes and dry mouth), abnormal pupillary light response, upper gastrointestinal symptoms, and neurogenic bladder. Chronic AAN segregated into two subgroups. One subgroup (N = 4) had low antibody titer (0.09 +/- 0.01 nmol/L) and a paucity of cholinergic symptoms. It was indistinguishable from pure autonomic failure. The other subgroup (N = 4) had high antibody titer (11.6 +/- 2.08 nmol/L), sicca complex, abnormal pupils, and neurogenic bladder; three had severe upper gastrointestinal dysfunction. Higher antibody titers correlated with greater autonomic dysfunction and more frequent cholinergic dysautonomia. These observations expand the clinical spectrum of AAN to include chronic cases, some being indistinguishable from pure autonomic failure, and support the concept that ganglionic AChR antibodies are important diagnostically and pathophysiologically in acquired dysautonomia.

Adolescent↗

Changes in the pupillary light reflex of pigmented royal college of surgeons rats with Age.

We studied the latency and amplitude of the pupillary light reflex response of the Royal College of Surgeons rat from 10 to 52 weeks of age. The responses of these dystrophic rats were diminished compared to those of normal, non-dystrophic rats at all ages examined. This was most marked at the dimmest light intensity studied here and for the latency of dystrophic animals' responses. The latency deteriorated over the course of 52 weeks, although there was some evidence of improvement beyond 36 weeks of age. The amplitude of the dystrophic animals' responses also suggested some deterioration occurring up to 36 weeks of age, but with a substantial improvement beyond this time. In addition to these parameters, we also observed a break in the constriction phase of the pupillary light reflex that was unique to the dystrophic animals' responses. The frequency with which the anomaly occurred decreased in a light-dependent manner with age. The improvement of the pupillary light reflex at older ages, even when very few photoreceptors remain, may reflect compensatory events occurring in the inner retinal layers and/or in the central connections of the pupillary light reflex pathway. We suggest that the break in the constriction phase is a reflection of dual inputs driving the response, one of which is affected more by the degenerative events. This study provides baseline data on the effect of degeneration on function over time which can be used to evaluate the efficacy of repair strategies such as transplantation.

Aging↗

Misdirected regeneration of abducens nerve neurons into the parasympathetic pupillary pathway.

A 16-year-old girl suffered a severe head trauma with paralyses of the right oculomotor, trochlear, and abducens nerves. Three years later, only the abducens nerve had recovered. The pupil did not react to light or near. However, the diameter of the pupil correlated with horizontal gaze: with the gaze to the left, the diameter of the pupil was 8 mm, with the gaze straight ahead, 6 mm, and with the gaze to the right, 4 mm. With saccades to the right, the pupil started to constrict immediately and reached its smallest diameter after about 2 s. We conclude that the constriction of the pupil was due to misdirected regeneration of abducens nerve neurons into the parasympathetic pathway of the oculomotor nerve.

Abducens Nerve↗

Pupil abnormalities on the first postoperative day after cataract surgery.

Most, if not all, ophthalmologists strive to achieve a round pupil after cataract surgery with posterior chamber lens implantation. The presence of pupil abnormalities and iris modifications is cosmetically undesirable and may affect the quality of postoperative vision. The pupillary motility may be changed which will in turn affect both pupillary light reflexes and pupillary dilatation during fundus examination. In this paper, we prospectively studied 2 groups of patients who underwent uncomplicated cataract surgery with posterior chamber lens implantation; 100 patients who had planned extracapsular cataract extraction (ECCE), and 130 patients who underwent phacoemulsification. On the first postoperative day, we found a 16% rate of pupil abnormalities in the group which underwent ECCE surgery while only 5.3% of the phacoemulsification group had pupil abnormalities. There were different causes in which the two groups. The most common cause of pupil abnormality after ECCE was due to iris sphincter rupture, whereas the most common cause after phacoemulsification was due to iris trauma during phacoemulsification. These pupil abnormalities are the direct consequence of factors in surgery and we suggest ways to minimize the occurrence of such abnormalities in cataract surgery.

Cataract Extraction↗

Pseudoexfoliation syndrome with poorly dilating pupil: a light and electron microscopic study of the sphincter area.

BACKGROUND: The study was carried out to examine histological changes in the iris sphincter muscle and surrounding tissue in eyes with pseudoexfoliation syndrome (PXS). METHODS: Seventeen patients with PXS, 14 of them having capsular glaucoma, were enrolled into the study. Iris biopsies were obtained during extracapsular cataract extractions (ECCE) requiring sphincterotomies. Thirteen biopsy specimens underwent histological examination by light microscopy, and four were examined with the electron microscope. Three iris biopsies from cadaver eyes and one obtained during ECCE from a patient with a miotic pupil (no PXS) served as control specimens on light microscopy. Electron microscopic controls included three iris specimens from cadavers. RESULTS: In the light microscopic examination, blood vessel walls were stained with Congo Red in seven of the 13 PXS specimens. In three of these seven specimens the stromal tissue was extensively fibrotized, and in two specimens fibrosis was moderate. Distinct stromal fibrosis was also observed in one and moderate fibrosis in two PXS specimens negative for amyloid. The control specimens were not positive for Congo Red, but stromal tissue was moderately fibrotized in one specimen. Light microscopy did not reveal differences in muscle tissue between PXS and control specimens. Electron microscopically, however, the muscle tissue was fibrotic or disorganized in three PXS specimens and in one control specimen. Fibrils, similar to the fibrillar component of pseudoexfoliation material described in previous studies, were found in intimate association with the capillary basal lamina in all of the PXS specimens showing muscular fibrosis. CONCLUSIONS: These findings support the theory that PXS is associated with amyloid, and in some PXS eyes miosis is connected with degenerative changes both in the stromal tissue and in the muscular layer of the iris.

Adult↗

Differentiation of ischemic from non-ischemic central retinal vein occlusion during the early acute phase.

We investigated prospectively in 128 patients (140 eyes) the role of six routine clinical tests in the differentiation of ischemic central retinal vein occlusion (CRVO) from non-ischemic CRVO during its early acute phase. There were four functional tests [visual acuity, visual fields, relative afferent pupillary defect (RAPD), electroretinography (ERG)] and two morphologic tests (ophthalmoscopy and fluorescein fundus angiography). We found that none of the six tests had 100% sensitivity and specificity in such a differentiation during the early, acute phase, so that no one test can be considered a "gold standard"; however, combined information from all six is almost always reliable. Overall, the four functional tests proved far superior to the two morphologic tests in differentiating ischemic from non-ischemic CRVO:RAPD was most reliable in uniocular CRVO (with a normal fellow eye), followed closely by ERG in all cases; combined information from RAPD and ERG differentiated 97% of cases; perimetry was the next most reliable, followed by visual acuity. The two morphologic tests performed worst; fluorescein angiography provided either no information at all on retinal capillary nonperfusion (in at least one-third of the eyes during the early, acute phase) because of multiple limitations, or sometimes provided misleading information. Ophthalmoscopic appearance is the least reliable, most misleading parameter.

Acute Disease↗

Pupillary abnormalities due to sympathetic dysfunction in different forms of idiopathic headache.

Idiopathic vascular-type headache is frequently associated with pupillary alteration, which is often presumed to be due to malfunction of the sympathetic nervous system. In this review the anatomical and neurotransmitter basis of oculosympathetic function is briefly discussed along with some of the common pharmacological and physiological pupillary tests used in its assessment. The clinical and subclinical features of the pupil abnormalities are analysed in idiopathic headache, which includes migraine, tension headache, cluster headache, and chronic paroxysmal hemicrania. Possible mechanisms underlying these alterations are suggested. Among secondary headaches, carotid dissection and aneurysm have to be excluded when unilateral headache is associated with a persistent ipsilateral oculosympathetic deficit. From the literature, specific responses to pupillary tests apparently are present in idiopathic headache. Pupillary tests may differentiate between the subtypes of idiopathic headache. The investigation of pupillary dysfunction may provide information on the physiopathological basis of headache.

Headache↗

Portable infrared pupillometry using Pupilscan: relation to somatic and autonomic nerve function in diabetes mellitus.

The relationship between dynamic pupillary function and peripheral nerve function was studied in 85 randomly-selected diabetic patients and 67 age-matched normals using a portable infrared pupillometer (Pupilscan Version 5). Seven measurements were chosen to represent different components of the pupillary constriction-redilatation curve after a standardized light stimulus. Constriction latency was significantly prolonged in diabetic patients (p = 0.05), as was time to 63% redilatation (p = 0.001). Thermal thresholds at the feet weakly correlated with relative reflex amplitude (warm: r = -0.22, p = 0.05; cool: r = -0.23, p = 0.05), but vibration perception thresholds were more strongly associated with constriction and redilatation velocity (r = -0.42, p = 0.001; r = -0.28, p = 0.03). Among the cardiovascular autonomic function tests, only respiratory R-R variation correlated with constriction velocity (r = 0.47, p < 0.001), and Valsalva ratio with redilatation velocity (r = 0.25, p = 0.04), but postural systolic blood pressure change was also correlated with reflex amplitude and latency time (r = -0.42, p < 0.001; r = 0.41, p = 0.001). There were no significant associations with three measures of sweating function in the feet. Pupil measurements were abnormal in 4-11% of diabetic patients, while other neurological tests were abnormal in 8-35%, consistent with the length-dependence of diabetic neuropathy. Median coefficients of variation were 2.0-7.2% in diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Electroretinography in central retinal vein occlusion. Correlation of electroretinographic changes with pupillary abnormalities.

In 149 eyes with central retinal vein occlusion (CRVO), we prospectively investigated the role of routine, clinical electroretinography (ERG) in differentiating ischemic (60 eyes) from nonischemic CRVO (89 eyes). Single-flash photopic and scotopic ERGs were recorded. Data for the amplitudes and implicit times of a- and b-waves and for the b-/a-wave amplitude ratio were analyzed in detail. The study revealed that the best ERG parameter (for both photopic and scotopic ERG) for differentiating ischemic from nonischemic CRVO was a subnormal b-wave amplitude (reduced to less than or equal to 60% or by greater than or equal to 1 SD from the normal mean value, or less than or equal to 64%-69% of that in the fellow normal eye), with a sensitivity of 80%-90% and a specificity of 70%-80%. ERG findings were correlated with the relative afferent pupillary defect (RAPD). An RAPD of greater than or equal to 0.7 log units showed a sensitivity of 88% and a specificity of 90% in differentiating ischemic from nonischemic CRVO. ERG and RAPD findings showed a good correlation. The combined ERG and RAPD tests could differentiate 97%-100% of ischemic from nonischemic CRVO cases, with a specificity of about 70%.

Aged↗

Naloxone induces miosis in normal subjects.

In a placebo-controlled trial, pupillary constriction was measured in healthy non-addicted subjects and in opiate addicts by using static computer-assisted pupillometry. In contrast to earlier reports, a clear-cut pupillary constriction was observed in healthy persons after a single intravenous injection of 0.4 mg naloxone. No significant changes of pupillary size were recorded in the same subjects after the administration of a placebo. In methadone-maintained subjects, the IV administration of 0.4 mg naloxone caused a significant pupillary dilatation. From these data it can be concluded that naloxone seems to have a central pharmacological action not only in opiate addicts, but also in healthy persons. This is demonstrable by studying the miotic response.

Adult↗

Opioid physical dependence development in humans: effect of time between agonist pretreatments.

We examined the effect of morphine pretreatment spacing on intensity of subsequent precipitated withdrawal response to test the hypothesis that withdrawal intensity would be inversely related to pretreatment spacing. Subjects were ten nondependent male volunteers who reported using opioids an average of 2.5 times per week. Three IM morphine injections (each 18 mg/70 kg) were administered during each of four experimental conditions. The experimental conditions involved spacing injections at 12-, 24-, 48- or 72-h intervals. Naloxone (10 mg/70 kg IM) was administered 24 h after the last morphine exposure. A comparison condition was included in which a naloxone challenge was given at 24 h following a single IM morphine pretreatment (18 mg/70 kg). Subject rated measures of symptoms and observer-rated measures of signs indicated that withdrawal intensity was inversely related to the morphine spacing interval and in particular that intensity of withdrawal precipitated after three pretreatments spaced at 12-h intervals was greater than that precipitated after a single morphine pretreatment. Physiological data supported a more intense withdrawal response in the 12-h spacing condition and provided evidence of overshoot on blood pressure and skin temperature measures. These findings are pertinent to the transition between acute and chronic physical dependence; they suggest that there is a temporal window during which repeated opioid administrations result in escalation of physical dependence but that dependence levels after widely spaced multiple exposures may be no greater than after a single exposure.

Adult↗

Opioid physical dependence development: effects of single versus repeated morphine pretreatments and of subjects' opioid exposure history.

In acute dependence, signs and symptoms of opioid withdrawal are precipitated when an opioid antagonist (naloxone) is administered following acute (e.g. single dose) pretreatment with a mu agonist. This study examined the influence of amount of previous opioid exposure, both immediate and remote, on intensity of precipitated withdrawal effects in an acute dependence model. Two groups of subjects, opioid abusers (n = 20) and nonabusers (n = 20), received either one 15 mg/70 kg IM morphine pretreatment or two such pretreatments spaced 24 h apart. Naloxone challenge (30 mg/70 kg) followed 4.33 h after the second pretreatment. There were clear effects of morphine pretreatment condition (single versus repeated 15 mg) on the intensity of precipitated withdrawal responses elicited by naloxone. More intense effects were seen after the repeated pretreatment, suggesting that physical dependence escalates with repeated opioid exposures spaced at appropriate intervals. Subjects with an opioid abuse history reported greater liking of agonist drug effects than did nonabusers, whereas nonabusers reported more sedating effects. However, an opioid abuse history did not influence the intensity of precipitated withdrawal symptoms and signs. The latter finding suggests that a previous opioid exposure history does not dramatically modulate initial stages of physical dependence development during subsequent opioid exposure episodes.

Adult↗

[Cardiovascular and pupillary autonomic and somatosensory neuropathy in chronic diseases with autoimmune phenomena. A comparative study of patients with Crohn disease, ulcerative colitis, systemic lupus erythematosus, progressive systemic sclerosis and type I diabetes mellitus].

BACKGROUND: During the last years, examination of autonomic nervous function and of autonomic neuropathy has attracted attention not only in diabetes mellitus research but also in other areas of internal medicine. However, patients with various chronic diseases with autoimmune phenomenons have never been investigated in a comparative study with standardized examination techniques. Hence, the aim of the study was to examine the prevalence and the severity of autonomic neuropathy in patients with the following chronic diseases. PATIENTS AND METHODS: We investigated 28 patients with Crohn's disease (CD: age: 32.4 +/- 2.0 y), 17 patients with ulcerative colitis (UC: 39.7 +/- 3.6 y), 39 patients with systemic lupus erythematosus (SLE: 34.9 +/- 2.0 y), 38 patients with progressive systemic sclerosis (pSS; 51.5 +/- 2.4 y) and 65 patients with insulin-dependent diabetes mellitus (IDDM: 35.5 +/- 1.6 y). Cardiovascular autonomic (cANP), pupillary autonomic (pANP), and sensorimotor (ssNP) neuropathy were assessed by standardized techniques. RESULTS: Prevalence rates for cANP, pANP and ssNP were found to be 0%, 19%, and 7% in CD, 6%, 25%, and 18% in UC, 5%, 29%, and 10% in SLE, 11%, 16%, and 32% in pSS, and 26%, 66%, and 29% in IDDM, respectively. CONCLUSION: The study demonstrated patients with IDDM to have the highest prevalence rates of cANP and pANP. Patients with other chronic diseases, particularly SLE, pSS and UC, had high prevalence rates of pANP. This may be due to alterations of structures of the central nervous system in these patients. cANP was rare in patients with inflammatory bowel disease and ssNP was found very often in patients with pSS, probably due to local fibrotic lesions. The various disease groups differ in the pattern and severity of autonomic and sensorimotor neuropathy, which indicates that different structures and neuropathogenic mechanisms may be involved.

Adult↗

[Impairment of safety in navigation caused by alcohol: pupillography and measurement of pupil movements].

OBJECTIVE: To evaluate data in an interdisciplinary project (ophthalmology, forensic medicine, internal medicine, psychology,and nautical science) in order to identify critical blood alcohol limits in sea navigation. METHODS: A sea traffic simulator was employed for realistic nautical demands on 21 professional experienced skippers under sober and alcoholized conditions (target blood alcohol concentration: 1.0 per thousand ). After simulated navigation, pupil light reflex, spontaneous pupil movements,nystagmus,and saccades were evaluated by pupillography. Modification of the pupillograph enabled us also to measure optokinetic nystagmus. RESULTS: Evaluation of the pupil light reflex revealed obvious changes in the extent of relative contraction and in redilatation time under the influence of alcohol. Diminished vigilance could be observed in all of the skippers when optokinetic nystagmus was tested. CONCLUSION: The pupillograph represents a suitable device for measuring functions of the visual and vegetative systems. Thus, the impact of these functions on nautical capability can be demonstrated. If further investigations such as ophthalmological, medical, psychological, and nautical evaluations are taken into account, it could be determined that blood alcohol levels of 1.0 per thousand may exclude safe navigation.

Accidents↗

[Measurement of scotopic pupils: comparison of scotic pupil measurements using a colvard pupilometer and the slitlamp green light test].

PURPOSE: The aim of the study was to compare the accuracy and the reproducibility of scotopic pupil measurements using two different methods. PATIENTS AND METHODS: We developed a simple test to measure scotopic pupil diameters using a narrow slit of light through a green filter of the Haag-Streit slitlamp. A total of 100 eyes from 50 refractive surgery candidates were prospectively examined by 2 independent investigators using both the Colvard pupilometer (Oasis/USA) and Sekundo's slitlamp green light test. Results were compared using all pairwise multiple comparison procedures (Student-Newman-Keuls method, SigmaStat/Jandel Scientific). The mean age of the patients was 36.3 years with a male:female ratio of 16:34. The colour of the iris was considered blue for 36 individuals and brown for the remainder. RESULTS: Reproducibility: the right eye mean pupil diameter using Sekundo's method was 6.4 mm (+/-0.9) measured by both the first (Slit 1R) and the second (Slit 2R) investigator. The left eye mean pupil diameter was 6.5 mm (+/-1) (Slit 1L) and 6.35 mm (+/-1) (Slit 2L), respectively. The following measurements were obtained with the Colvard pupillometer: (Colv1R)=6.25+/-0.85 mm, (Colv2R)=5.99+/-1 mm, (Colv1L)=6.15+/-0.91 mm, (Colv2L)=6.05+/-0.9 mm. There were no statistically significant differences between the two investigators within the same method of examination. Comparability:The data of both investigators were combined to form 4 groups: (Slit R)=6.4+/-0.96 mm, (Slit L)=6.4+/-1 mm, (Colv R)=6.05+/-0.9 mm, (Colv L)=6.1+/-0.93 mm. There was a significant difference ( p=0.024) between the two methods for both right and left eyes. Particularly for large pupils, the slitlamp green light measurements were significantly higher (up to 0.35 mm) than those with Colvard's device. CONCLUSIONS: The slitlamp green light test provides similar reproducibility for the measurement of the scotopic pupil diameter as the commercially available Colvard pupilometer.

Adult↗

[Cataract surgery in narrow pupil and postoperative fibrin reaction, especially after sphincterectomy].

BACKGROUND: Since increased intraoperative iris irritation can lead to increased postoperative inflammation, we are interested in postoperative reactions to several varied surgical procedures. We performed pupil stretching, iridotomy with iris suture, and partial sphincterectomy. MATERIALS AND METHODS: From January 1995 to January 1996, 100 patients (103 eyes) with narrow pupils underwent cataract surgery. In 13 eyes a iridotomy and iris suture were performed, in 28 eyes a partial sphincterectomy. In 62 eyes there was no surgical intervention after pupil stretching. Postoperative examinations were carried out in the early postoperative phase (up to 5 days postoperative) as well as 4 weeks after surgery. Fibrin reaction was classified according to 3 grades, (1) faint fibrinous threads, (II) fibrinous net, and (III) membranous fibrin exsudation. RESULTS: In the group without additional surgery there was a fibrinous reaction of grade I and II in 11 eyes. This complication occurred after iridotomy and iris suture in four cases and after sphincterectomy in four cases. While the intensity of fibrinous reaction was comparable in the first two groups, the fibrinous reaction after sphincterectomy was more intensive in one eye (grade III). However, response to intensive local antiphlogistic therapy was good. Frequency of fibrinous reaction in the three groups was statistically not significant. It should be pointed out that there was a partial restoration of pupil movements through sphincterectomy: mean pupil diameter was 4 mm, and 2.5 mm under exposure to light. Three patients had no pupillary reaction at all. CONCLUSIONS: Partial sphincterectomy facilities intraoperative manipulations of cataract surgery. Postoperative inflammatory reaction is rare and was very responsive to medical treatment. The reconstruction of pupillary movement is part of full visual function and, last but not least a round pupil is aesthetically more desirable.

Aged↗

[Partial sphincterectomy in cataract surgery. Clinical and patho-histologic results].

BACKGROUND: We perform partial sphincterectomy during cataract surgery in cases with very small pupil (< 3 mm). We assume that the small pupil is mainly due to a fibrosis ring of the sphincter muscle. PATIENTS: In 35 patients we performed the complete ophthalmological routine checkup. The pupil diameter was analysed by perimeter: a base value, with light, and in pharmaceutical mydriasis. Moreover 15 preparations were analysed histologically. RESULTS: Average pupil diameter was: base value 3.76 mm, with light 3.24 mm, in pharmaceutical mydriasis 4.84 mm. The showed pathohistological examination that in all excisions a part of the sphincter muscle was verifiable. We found fibrosis of different grades in various locations. CONCLUSION: In most cases functional pupil movement can be verified after operation. In an intended partial sphincterectomy part of the sphincter muscle can be excised. The different pupil diameter is due to the different degree of fibrosis of the sphincter muscle.

Adult↗