Projections of the postero-medial lateral suprasylvian area (PMLS) to cortical area 20 in cats with special reference to pupillary constriction: a physiological and anatomical study.

Projections of the pupillo-constrictor area in the postero-medial lateral suprasylvian area (PMLS) to that in cortical area 20 was studied using electrophysiological and anatomical methods. Cats were injected with wheatgerm agglutinin-conjugated horseradish peroxidase in the latter area, which was located by intracortical stimulation. Retrogradely labeled cells were found in the PMLS pupillo-constrictor area. It was concluded that the pupillo-constrictor area in the PMLS has direct projections to that in area 20.

Testing pupillary autonomic function with a retinal camera.

A method for testing pupillary autonomic function with the Canon CR3-45NM retinal camera is described. Results agreed well with those obtained using the Polaroid CU5 closeup camera in 20 non-diabetic subjects and 29 diabetic patients (intrapair correlation coefficient = 0.97).

Vegetative imbalance in migraine. A dynamic TV pupillometric evaluation.

In this study we investigated the variations of pupillary diameter obtained in different experimental conditions (dark/light adaptation, light reflex, sural nerve stimulation) in a group of migraine patients with unilateral location of pain in almost all the attacks and in healthy controls by means of a TV pupillometric device. The data obtained seems to document the existence in migraine of unbalanced vegetative function ascribable either to a strong sympathetic activity or to a parasympathetic deficiency. Moreover, an involvement of central integrative pathways regulating pupil functioning cannot be excluded.

Electronic pupillometry in healthy controls. Response to sympathicomimetics.

The ocular sympathetic function was examined in 79 healthy volunteers (37 males and 42 females) by electronic pupillography. Pupillary diameters were first estimated under standard light conditions prior to drug application, these diameters being termed "basal values". Then, the pupils were stimulated pharmacologically by instillation of various sympathicomimetic drugs: tyramine tests were carried out in 42 individuals (24 females; 18 males), hydroxyamphetamine tests in 38 (22 females and 16 males), and phenylephrine tests in 43 individuals (23 females and 20 males). Generally, only a minor variation in the frequency of asymmetries was observed between sexes as well as between the various age groups, both when calculating the increase in pupillary diameter in millimeters, in per cent, and as the anisocoria index. In agreement with previous investigations, pupil size was found to diminish with age. The use of an age-matched control material is mandatory when comparing pupillographic recordings in patients in various categories, in the ordinary condition, as well as after topical drug administration.

Dysfunction of the sympathetic nervous system in cluster headache.

Ocular sympathetic function was studied in 13 cluster headache patients during and between attacks and several weeks or months after attacks had subsided. The pupillary response to tyramine eyedrops and facial sweating and flushing in response to body heating and to the taste of chilies were also investigated during remission. Pupillary dilatation lag on the symptomatic side persisted between bouts and correlated significantly with loss of thermoregulatory sweating in the lower part of the forehead. In six patients in remission, pupillary dilatation in response to tyramine eyedrops was impaired on the symptomatic side, whereas five patients showed no sign of ocular sympathetic deficit. These findings indicate that incomplete sympathetic deficit persisted on the symptomatic side in a subgroup of cluster headache patients during remission. In most of this subgroup the pattern of sympathetic deficit was consistent with impaired function of postganglionic cervical sympathetic fibres.

Pupil responsiveness in cluster headache: a dynamic TV pupillometric evaluation.

In this study the variations in pupil diameter induced by different stimuli (dark-light adaptation, light reflex, electric stimulation of the sural nerve) were investigated in episodic (in the active or remission phases) and in chronic cluster headache (CH) patients. Pupil size monitoring was performed with a monocular, infrared TV pupillometer, and sural nerve stimuli were applied after the pain threshold had been measured as the flexion reflex threshold of the biceps femoris muscle (RIII reflex). The results were compared with those obtained in patients with "peripheral" (third neuron) Horner's syndrome and in healthy sex- and age-matched controls. On the symptomatic side we found an impairment of pupil response to light flashes and nociceptive stimuli; similar findings were sometimes evident on the pain-free side, too. These results substantiate previous observations that in cluster headache a dysfunction of the integrative central nervous system pathways also exists intercritically and mostly bilaterally, involving both autonomic regulation and pain perception mechanisms.

Cluster headache: combined assessment with pupillometry and evaporimetry.

Twenty-nine patients with cluster headache have been examined with the pupillometer and the evaporimeter. Pupils were dilated by sympathicomimetic drugs instilled into the conjunctival sacs, and responses of the two sides were compared. Forehead sweating was stimulated by body heating and by pilocarpine injection, and sweat evaporation on the two sides was compared. Most patients demonstrated the known patterns of hyposecretion on heating, of pilocarpine supersensitivity, and of deficient pupillary dilatation on OH-amphetamine stimulation on the symptomatic side and a supersensitivity of this pupil to phenylephrine. There were deviations from the rule for all methods of testing. Sixteen patients demonstrated a typical supersensitivity response of the pupil and of the sweat glands on the symptomatic side. Six patients had no such response, and seven patients had a discrepancy between the pupillary and the sweat gland response to stimulation, supersensitivity being present in one system only. There was a high degree of concordance between the results of the various methods of examination.

Chronic paroxysmal hemicrania. XIII. The pupillometric pattern.

Pupillometric studies were carried out in eight patients with chronic paroxysmal hemicrania (CPH) and in age- and sex-matched controls in the basal condition and after instillation of 2% tyramine (CPH, n = 5; controls, n = 17), 1% OH-amphetamine (CPH, n = 6; controls, n = 12), and 1% phenylephrine (CPH, n = 6; controls, n = 17). The pupil on the symptomatic and non-symptomatic sides in CPH patients was significantly smaller in the basal condition than in controls, particularly on the symptomatic side. The mydriatic responses to pharmacologic stimulation were essentially similar on the symptomatic and non-symptomatic sides. An evaporimetric study of the forehead sweat glands, using the body heating and pilocarpine tests, was also carried out in these patients and in age- and sex-matched controls. "Early", "intermediate", and "late" measurements demonstrated symmetry of forehead sweating. The findings for both methods of examination thus contrast with those in cluster headache patients. Pupillometric and forehead sweating patterns therefore suggest differences in the pathogenesis of the two headache entities. These tests may be used to distinguish CPH and cluster headache clinically.

Respiratory fluctuations of the human pupil.

We simultaneously recorded respiration and pupil size in six normal subjects with an age range of 23-40 years (mean = 30.1), to study the relationship between the respiratory rhythm and changes in pupil size. In all subjects, respiratory fluctuations of the pupil (inspiratory mydriasis and expiratory miosis) were observed during normal spontaneous respirations. The amplitude of these pupillary changes was closely proportional to the tidal volume.

Opposite pupillary size effects in the cat and dog after microinjections of morphine, normorphine and clonidine in the Edinger-Westphal nucleus.

The Edinger-Westphal complex (EW) was explored as a possible site of action for the effects of morphine and clonidine to produce mydriasis in the cat and miosis in the dog. Morphine, normorphine and clonidine, dissolved in 0.5 microliter 0.9% NaCl, were injected via chronic indwelling cannulae into or near the EW of the restrained cat and dog. In the cat, all 3 drugs produced a dose-dependent mydriasis. Clonidine (3-30 nmol) was 1.7 times more potent than normorphine (3-30 nmol) and 9.6 times more potent than morphine (10-60 nmol). Normorphine was 5.5 times more potent than morphine. Significant miosis resulted from single doses of morphine (17.5 nmol), normorphine (15.5 nmol) and clonidine (19 nmol) injected in the EW of the dog. Injections sites closest to the EW yielded the greatest changes in pupillary diameter. Naloxone antagonized the pupillary effects of normorphine in the cat and dog but had no effect on clonidine mydriasis in one cat. It was concluded that the EW region is an important site of action for the effects of morphine and clonidine on pupil diameter in both species. However, the neurocircuitry and neurochemistry of the EW probably differ between the cat and dog.

The pupil cycle time in familial dysautonomia. Further evidence for denervation hypersensitivity.

The pupil cycle time (PCT) was prolonged in 11 subjects with familial dysautonomia. In the younger age group (10-19 years), mean PCT was 872 +/- 88 msec as compared to 15 normal age matched controls (728 +/- 88). In the 3 oldest patients (30-39 years) mean PCT was 980 +/- 133 msec as compared to 13 age matched normals (748 +/- 56). It is proposed that prolongation of PCT in familial dysautonomia may be due to functional denervation of the iris or that it is a result of a structural abnormality of its musculature and/or its neuromuscular junctions.

Pupillographic analysis of morphine action in the rabbit: role to the autonomic nervous system.

Pupillary response of albino rabbits were recorded using an infrared video pupillometer. The transient response to an i.v. injection of morphine (1-12 mg/kg) consists of three phases. Phase 1 is a brief mydriasis of 20 s duration. Phase 2 is a miosis that reaches a maximum within 2-4 min and is the only dose-related endpoint observed. Time-averaged pupil size is not decreased by morphine in a dose-related manner when measured 5 min after injection. Phase 3 is large amplitude fluctuation that reaches peak amplitude within 20 min and may last for several hours. Thus, dynamic pupillography reveals that the terms "miosis' and "mydriasis' may be insufficient to fully describe opiate-induced pupillary effects. All three phases are blocked by naloxone (0.1 mg/kg i.v.) and by topical pretreatment with scopolamine. These results are consistent with the theory that morphine alters pupil size by interaction with opiate receptors that are involved in the control of parasympathetic output to the iris.

Anisocoria with orbital floor fractures: worry and wait.

We present a new complication: transient pupillary dilatation in an eye that sustained a posterior orbital floor blow-out fracture. By reviewing the neural pathways involved with pupillary motor function, we surmise the causes of this complication to include trauma to the ciliary ganglion, short ciliary nerves, or the parasympathetic motor root. This type of injury has only recently been reported in the ophthalmologic literature, and has not, prior to this report, been included in the otolaryngologic literature.

Interaction of desipramine and amitriptyline with adrenergic mechanisms in the human iris in vivo.

Mydriatic responses of the pupil were evoked by locally instilled noradrenaline and methoxamine in eight healthy volunteers. The effects of three single oral doses (25 mg, 50 mg and 100 mg) of amitriptyline and desipramine were compared on the mydriatic responses. Both antidepressants potentiated the mydriasis evoked by noradrenaline; desipramine appeared to be approximately four times more potent than amitriptyline. Both antidepressants antagonised the mydriasis evoked by noradrenaline; desipramine appeared to be approximately four times more potent than amitriptyline. Both antidepressants antagonised the mydriasis evoked by methoxamine, amitriptyline being approximately twice as potent as desipramine. It is suggested that the potentiation of the response to noradrenaline may reflect the blockade of the uptake of noradrenaline into adrenergic nerve terminals, whereas the antagonism of the response to methoxamine may reflect the blockade of postsynaptic alpha-adrenoceptors by the antidepressants. It is argued that the interaction of the antidepressants with adrenergic mechanisms could explain why amitriptyline, a potent anticholinergic agent, causes no significant change in resting pupil diameter, while desipramine, a relatively weaker anticholinergic agent, produces a significant mydriasis.

A horseradish peroxidase study of the innervation of the internal structures of the eye. Evidence for a direct pathway.

The sources of innervation of the internal structures of the eye in monkey and rabbit were investigated by injecting horseradish peroxidase (HRP) intraocularly and monitoring its retrograde transport. HRP-labeled cells were found in the ciliary ganglia and in the midbrain throughout the dorsoventral extent of the midline of the oculomotor complex. The results suggest that a direct pathway exists from the midbrain, and it is argued that this pathway is for the control of accomodation. Either this pathway is direct, with no synapse interposed, or the postsynaptic neurons are near or in the intrinsic musculature. A third but not so likely possibility is that retrograde transsynaptic transport of HRP occurred across electrotonic synapses in the ciliary ganglion. These findings may challenge the commoly held view that the entire pathway for the control of the intrinsic musculature synapses in the ciliary ganglion. On the other hand, it may be that this direct path is a sensory system much like the mesencephalic nucleus of the trigeminal nerve.

Diagnosis of pupillary anomalies.

Lesions of the afferent, intercalated, efferent (parasympathetic), and cervical sympathetic arms of the pupillary pathway each tend to produce rather distinctive clinical signs. Sophisticated equipment generally is not needed to define the probable basis for anisocoria and/or disordered pupillary function. Diagnosis of the more common anomalies of the pupil usually can be made from observations obtained using only a penlight, occluder, slit lamp biomicroscope, and a few diagnostic pharmaceutical agents. This paper has been written as a guide to recognition of pupillary signs and as an aid to the practitioner who must differentiate among those that mandate immediate referral, those which require careful analysis on a less urgent basis, and those that can be regarded, for all practical purposes, as benign.

Responsiveness of the rabbit eye to adrenergic and cholinergic agonists after treatment with 6-hydroxydopamine or alpha-methyl-para-tyrosine: Part I--Pupillary changes.

The responses of rabbit pupils to graded doses of both adrenergic and cholinergic drugs after chemical sympathectomy with 6-hydroxydopamine have been examined. For comparison, similar data were obtained in rabbits treated chronically with the norepinephrine synthesis inhibitor, alpha-methyl-para-tyrosine. While quantitative differences were apparent, the effects of these 2 treatments were qualitatively similar. In both cases, a marked reduction in the responsiveness of the iris to cholinergic agonists accompanied the development of supersensitivity to adrenergic amines.

Cholinergic supersensitivity of the iris sphincter in Adie's tonic pupil.

In patients with unilateral Adie's syndrome, we compared the relative supersensitivity of the tonic pupil to methacholine hydrochloride (Mecholyl 2.5%) and pilocarpine 0.125%. We tested a large series of patients and photographed the pupils before and 30 minutes after the eyedrops. In a group of 36 patients, Mecholyl was positive in 64% of the tests; and in a group of 20 patients, pilocarpine 0.125% was positive in 80% of the tests. Eight patients who failed to show supersensitivity with Mecholyl were tested with pilocarpine and five of the eight were shown to be supersensitive. We concluded that pilocarpine, in this concentration is not only an adequate substitute for Mecholyl 2.5%, but is a more sensitive testing substance in unilateral cases, simply because it has a slightly stronger miotic action.