Disturbance of pupillary responses

The normal pupil always reacts to light (direct and consensual reactions) and to convergence.

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The causes of pupillary reflex disorders are:

1. Lesions of the optic nerve. The blind eye does not respond to direct light when illuminated in isolation and there is no consensual contraction of the sphincter of the other eye, but the blind eye responds with a consensual reaction if its third nerve is intact and if the other eye and its optic nerve are not damaged.
2. Lesions of the oculomotor nerve. When the third nerve is damaged, the direct and consensual reaction to light is absent on the affected side due to paralysis of the sphincter of the pupil, but the direct and consensual reaction remains intact on the opposite side.
3. Other reasons include:
   • Eddie's syndrome.
   • It is necessary to note a special type of pupillary disorders, when there is paralysis of pupillary reflexes with the absence of reactions to light, but preserved reaction to convergence. This pathology is described in various conditions: neurosyphilis, Eddie syndrome, diabetes mellitus, pinealoma, pathological regeneration after damage to the oculomotor nerve, encephalitis, multiple sclerosis, ophthalmic herpes, eye trauma, dystrophic myotonia, pandysautonomia (familial autonomic dysfunction Riley-Day syndrome), Fisher syndrome, type I HMSN (Charcot-Marie-Tooth disease).

Some pupillary phenomena in patients in coma

The shape, size, symmetry, and reaction of the pupils to light reflect the state of the oral parts of the brainstem and the functions of the third nerve in patients in coma. The reaction of the pupils to light is very sensitive to structural damage in this area of the brain, but at the same time very resistant to metabolic disorders. Disturbance of this reflex, especially when it is unilateral, is the most important sign that allows us to differentiate metabolic comas from comatose states caused by structural damage to the brain.

1. Small pupils that react well to light in an unconscious patient ("diencephalic pupils") usually indicate the metabolic nature of the coma.
2. The appearance of miosis and anhidrosis of the hemitype (Horner's syndrome), ipsilateral to brain damage, reflects involvement of the hypothalamus on that side and is often the first sign of incipient transtentorial herniation in supratentorial space-occupying processes causing coma.
3. Medium-sized pupils (5-6 mm) with spontaneous alpha-cillations of their size (hippus) become wider when pinched in the neck area (ciliospinal reflex). This phenomenon reflects damage to the midbrain tegmentum or pretectal areas.
4. A pronounced bilateral miosis (“pinpoint” pupils) with the inability to cause their reaction to light is characteristic of primary damage to the tegmentum of the pons (and cerebellum).
5. Horner's syndrome, ipsilateral to brain damage, may reflect a pathological process in the lateral parts of the pons, lateral part of the medulla oblongata and ventrolateral parts of the cervical spinal cord on the same side.
6. A sluggish pupillary response to light or its absence with a widely dilated pupil (7-8 mm) is due to the preservation of the sympathetic pathways (Hutchison's pupil). At the same time, the oval shape of the pupil is due to uneven paresis of the sphincter of the pupil, which leads to an eccentric antagonistic effect of the dilator of the pupil. This phenomenon indicates a peripheral lesion of the parasympathetic fibers going to the sphincter of the pupil as part of the third nerve.
7. Fixed pupils of medium width that do not react to light may be observed with direct damage to the midbrain (tumors, hemorrhages, infarctions). Damage to the oculomotor nerves between their nuclei causes ophthalmoplegia. Such paralysis of the third nerve is often bilateral, unlike their peripheral paralysis, which usually occurs on one side.

Impaired pupillary response

1. Simultaneous disturbance of pupillary response to light, convergence and accommodation is clinically manifested by mydriasis. In case of unilateral damage, reaction to light (direct and friendly) is not caused on the affected side. This immobility of pupils is called internal ophthalmoplegia. This reaction is caused by damage to parasympathetic pupillary innervation from the Yakubovich-Edinger-Westphal nucleus to its peripheral fibers in the eyeball. This type of pupillary response disturbance can be observed in meningitis, multiple sclerosis, alcoholism, neurosyphilis, cerebrovascular diseases, and craniocerebral trauma.
2. Disturbance of the consensual reaction to light is manifested by anisocoria, mydriasis on the diseased side. In the intact eye, the direct reaction is preserved and the consensual reaction is weakened. In the diseased eye, the direct reaction is absent, but the consensual reaction is preserved. The cause of such dissociation between the direct and consensual reactions of the pupil is damage to the retina or optic nerve before the crossing of the optic fibers.
3. Amaurotic pupillary immobility to light is found in bilateral blindness. In this case, both direct and consensual pupillary reactions to light are absent, but convergence and accommodation reactions are preserved. Amaurotic pupillary areflexia is caused by bilateral damage to the visual pathways from the retina to the primary visual centers inclusive. In cases of cortical blindness or damage to the central visual pathways on both sides, going from the lateral geniculate shaft and from the thalamus cushion to the occipital visual center, the reaction to light, direct and consensual, is completely preserved, since the afferent visual fibers end in the area of the anterior colliculus. Thus, this phenomenon (amaurotic immobility of the pupils) indicates a bilateral localization of the process in the visual pathways up to the primary visual centers, whereas bilateral blindness with the preservation of direct and consensual pupillary reactions always indicates damage to the visual pathways above these centers.
4. Hemiopic pupillary reaction consists in the fact that both pupils contract only when the functioning half of the retina is illuminated; when the fallen half of the retina is illuminated, the pupils do not contract. This pupillary reaction, both direct and consensual, is caused by damage to the optic tract or subcortical visual centers with the anterior colliculus, as well as crossed and uncrossed fibers in the chiasm region. Clinically, it is almost always combined with hemianopsia.
5. Asthenic pupillary reaction is expressed in rapid fatigue and even complete cessation of constriction with repeated light exposure. Such a reaction occurs in infectious, somatic, neurological diseases and intoxications.
6. The paradoxical reaction of the pupils is that when exposed to light, the pupils dilate, and in the dark they constrict. It is extremely rare, mainly in hysteria, and also sharply in tabes dorsalis, strokes.
7. With increased pupillary light reaction, the reaction to light is more vivid than normal. It is sometimes observed in mild concussions, psychoses, allergic diseases (Quincke's edema, bronchial asthma, urticaria).
8. The tonic pupillary reaction consists of an extremely slow dilation of the pupils after their constriction under light exposure. This reaction is caused by increased excitability of the parasympathetic pupillary efferent fibers and is observed mainly in alcoholism.
9. Myotonic pupillary response (pupillotonia), pupillary disorders of the Adie type can occur in diabetes mellitus, alcoholism, vitamin deficiencies, Guillain-Barré syndrome, peripheral autonomic dysfunction, rheumatoid arthritis.
10. Argyll Robertson type pupillary disorders. The clinical picture of Argyll Robertson syndrome, which is specific for syphilitic lesions of the nervous system, includes such signs as miosis, slight anisocoria, lack of reaction to light, pupil deformation, bilateral disorders, constant pupil sizes during the day, lack of effect from atropine, pilocarpine and cocaine. A similar picture of pupillary disorders can be observed in a number of diseases: diabetes mellitus, multiple sclerosis, alcoholism, cerebral hemorrhage, meningitis, Huntington's chorea, pineal gland adenoma, pathological regeneration after paralysis of the extraocular muscles, myotonic dystrophy, amyloidosis, Parinaud's syndrome, Munchmeyer's syndrome (vasculitis, which underlies interstitial muscle edema and subsequent proliferation of connective tissue and calcification), Denny-Brown sensory neuropathy (congenital absence of pain sensitivity, no reaction of the pupils to light, sweating, increased blood pressure and increased heart rate with severe pain stimuli), pandysautonomia, familial dysautonomia Riley-Day, Fisher syndrome (acute development of complete ophthalmoplegia and ataxia with decreased proprioceptive reflexes), Charcot-Marie disease - Here. In these situations, Argyll Robertson syndrome is called non-specific.
11. Premortem pupillary reactions. The examination of pupils in comatose states acquires great diagnostic and prognostic significance. In case of deep loss of consciousness, severe shock, comatose state, the pupillary reaction is absent or sharply reduced. Immediately before death, the pupils in most cases strongly constrict. If in a comatose state miosis gradually gives way to progressive mydriasis, and the pupillary reaction to light is absent, then these changes indicate the proximity of death.

The following are pupillary disorders associated with parasympathetic dysfunction.

1. The reaction to light and the pupil size under normal conditions depend on adequate light reception by at least one eye. In a completely blind eye, there is no direct reaction to light, but the pupil size remains the same as on the side of the intact eye. In the case of complete blindness in both eyes with damage in the area anterior to the lateral geniculate bodies, the pupils remain dilated, not reacting to light. If bilateral blindness is caused by destruction of the occipital lobe cortex, the pupillary light reflex is preserved. Thus, it is possible to encounter completely blind patients with normal pupillary reaction to light.

Lesions of the retina, optic nerve, chiasm, optic tract, retrobulbar neuritis in multiple sclerosis cause certain changes in the functions of the afferent system of the pupillary light reflex, which leads to a disruption of the pupillary reaction, known as the pupil of Marcus Gunn. Normally, the pupil reacts to bright light by quickly narrowing. Here, the reaction is slower, incomplete and so short that the pupil can immediately begin to dilate. The cause of the pathological reaction of the pupil is a decrease in the number of fibers providing the light reflex on the affected side.

2. Damage to one optic tract does not change the pupil size due to the remaining light reflex on the opposite side. In this situation, illumination of intact areas of the retina will produce a more pronounced pupillary response to light. This is called the Wernicke pupillary response. It is very difficult to induce such a response due to the dispersion of light in the eye.
3. Pathological processes in the midbrain (the area of the anterior colliculus) can affect the fibers of the pupil's reflex arc of light reaction that cross in the area of the cerebral aqueduct. The pupils are dilated and do not react to light. This is often combined with the absence or limitation of upward eye movements (vertical gaze paresis) and is called Parinaud's syndrome.
4. Argyll Robertson syndrome.
5. In case of complete damage of the III pair of cranial nerves, pupil dilation is observed due to the absence of parasympathetic influences and continuing sympathetic activity. In this case, signs of damage to the motor system of the eye, ptosis, deviation of the eyeball in the lower-lateral direction are detected. Causes of severe damage to the III pair can be aneurysm of the carotid artery, tentorial hernias, progressive processes, Tolosa-Hunt syndrome. In 5% of cases of diabetes mellitus, isolated damage to the III cranial nerve occurs, the pupil often remains intact.
6. Adie's syndrome (pupillotonia) is a degeneration of the nerve cells of the ciliary ganglion. There is a loss or weakening of the pupil's reaction to light with a preserved reaction to the installation of the gaze at a close distance. Characteristic features include unilaterality of the lesion, dilation of the pupil, and its deformation. The phenomenon of pupillotonia is that the pupil narrows very slowly during convergence and especially slowly (sometimes only for 2-3 minutes) returns to its original size after the end of convergence. The size of the pupil is inconstant and changes during the day. In addition, pupil dilation can be achieved by prolonged exposure of the patient to darkness. Increased sensitivity of the pupil to vegetotropic substances is noted (sharp dilation from atropine, sharp constriction from pilocarpine).

Such hypersensitivity of the sphincter to cholinergic agents is detected in 60-80% of cases. In 90% of patients with tonic pupils of Adie, tendon reflexes are weakened or absent. Such weakening of reflexes can be widespread, affecting the upper and lower extremities. In 50% of cases, bilateral symmetrical damage is observed. It is unclear why tendon reflexes are weakened in Adie syndrome. Hypotheses have been proposed about widespread polyneuropathy without sensory impairments, degeneration of spinal ganglia fibers, a specific form of myopathy, and a defect in neurotransmission at the level of spinal synapses. The average age of the disease is 32 years. It is more often observed in women. The most common complaint, in addition to anisocoria, is blurred vision at close range when examining closely located objects. In approximately 65% of cases, residual paresis of accommodation is noted in the affected eye. After several months, there is a pronounced tendency for the strength of accommodation to normalize. In 35% of patients, astigmatism can be provoked in the affected eye with each attempt to look at a close object. This is presumably due to segmental paralysis of the ciliary muscle. When examined with a slit lamp, some difference in the pupillary sphincter can be noted in 90% of affected eyes. This residual reaction is always a segmental contraction of the ciliary muscle.

Over the years, the pupil of the affected eye becomes narrowed. There is a strong tendency for the other eye to become narrowed after a few years, so that the anisocoria becomes less noticeable. Eventually, both pupils become small and react poorly to light.

It has recently been shown that the dissociation of pupillary response to light and accommodation, often observed in Adie syndrome, can only be explained by diffusion of acetylcholine from the ciliary muscle into the posterior chamber toward the denervated pupillary sphincter. It is likely that diffusion of acetylcholine into the aqueous humor contributes to the tension of iris movements in Adie syndrome, but it is also clear that the dissociation cannot be explained so simply.

The pronounced pupillary response to accommodation is most likely due to pathological regeneration of accommodation fibers in the sphincter of the pupil. The nerves of the iris have an amazing capacity for regeneration and reinnervation: the heart of a fetal rat transplanted into the anterior chamber of an adult eye will grow and contract at a normal rate, which can change depending on rhythmic stimulation of the retina. The nerves of the iris can grow into the transplanted heart and set the heart rate.

In most cases, Adie syndrome is an idiopathic disease, and its cause cannot be found. Secondarily, Adie syndrome can occur in various diseases (see above). Familial cases are extremely rare. Cases of combination of Adie syndrome with vegetative disorders, orthostatic hypotension, segmental hypohidrosis and hyperhidrosis, diarrhea, constipation, impotence, local vascular disorders have been described. Thus, Adie syndrome can act as a symptom at a certain stage of development of peripheral vegetative disorder, and sometimes can be its first manifestation.

Blunt trauma to the iris can cause rupture of the short ciliary branches in the sclera, which will clinically manifest as deformation of the pupils, their dilation and impaired (weakened) reaction to light. This is called posttraumatic iridoplegia.

The ciliary nerves may be affected by diphtheria, causing pupil dilation. This usually occurs in the 2nd or 3rd week of the disease and is often combined with soft palate paresis. Pupil dysfunction usually fully recovers.

Pupillary disorders associated with sympathetic dysfunction

Sympathetic tract damage at any level manifests itself as Horner's syndrome. Depending on the level of damage, the clinical picture of the syndrome can be complete or incomplete. Complete Horner's syndrome looks like this:

1. narrowing of the palpebral fissure. Cause: paralysis or paresis of the upper and lower tarsal muscles receiving sympathetic innervation;
2. miosis with normal pupillary response to light. Cause: paralysis or paresis of the muscle that dilates the pupil (dilator); intact parasympathetic pathways to the muscle that constricts the pupil;
3. enophthalmos. Cause: paralysis or paresis of the orbital muscle of the eye, which receives sympathetic innervation;
4. homolateral facial anhidrosis. Cause: disruption of the sympathetic innervation of the facial sweat glands;
5. hyperemia of the conjunctiva, vasodilation of the skin vessels of the corresponding half of the face. Cause: paralysis of the smooth muscles of the vessels of the eye and face, loss or insufficiency of sympathetic vasoconstrictor effects;
6. heterochromia of the iris. Cause: sympathetic insufficiency, which results in disruption of the migration of melanophores into the iris and choroid, leading to disruption of normal pigmentation at an early age (up to 2 years) or depigmentation in adults.

Symptoms of incomplete Horner's syndrome depend on the level of damage and the degree of involvement of the sympathetic structures.

Horner's syndrome may have a central origin (damage to the first neuron) or a peripheral origin (damage to the second and third neurons). Large studies of patients with this syndrome hospitalized in neurological departments have revealed its central origin in 63% of cases. Its connection with stroke has been established. In contrast, researchers observing outpatients in eye clinics have found the central nature of Horner's syndrome in only 3% of cases. In Russian neurology, it is generally accepted that Horner's syndrome most frequently occurs with peripheral damage to sympathetic fibers.

Congenital Horner's syndrome. Its most common cause is birth trauma. The immediate cause is damage to the cervical sympathetic chain, which may be combined with damage to the brachial plexus (most often its lower roots - Dejerine-Klumpke paralysis). Congenital Horner's syndrome is sometimes combined with facial hemiatrophy, with anomalies in the development of the intestine, cervical spine. Congenital Horner's syndrome can be suspected by ptosis or heterochromia of the iris. It also occurs in patients with cervical and mediastinal neuroblastoma. All newborns with Horner's syndrome are offered to undergo chest radiography and screening to determine the level of excretion of almond acid, which is elevated in this case.

The most characteristic feature of congenital Horner's syndrome is heterochromia of the iris. Melanophores migrate to the iris and choroid during embryonic development under the influence of the sympathetic nervous system, which is one of the factors influencing the formation of the pigment melanin, and thus determines the color of the iris. In the absence of sympathetic influences, the pigmentation of the iris may remain insufficient, its color will become light blue. Eye color is established several months after birth, and the final pigmentation of the iris is completed by the age of two years. Therefore, the phenomenon of heterochromia is observed mainly in congenital Horner's syndrome. Depigmentation after disruption of the sympathetic innervation of the eye in adults is extremely rare, although some well-documented cases have been described. These cases of depigmentation indicate that some kind of sympathetic influence on melanocytes continues in adults.

Horner's syndrome of central origin. Hemispherectomy or extensive infarction of one hemisphere can cause Horner's syndrome on that side. Sympathetic pathways in the brainstem along its entire length go next to the spinothalamic tract. As a result, Horner's syndrome of brainstem origin will be observed simultaneously with a violation of pain and temperature sensitivity on the opposite side. The causes of such a lesion can be multiple sclerosis, pontine glioma, brainstem encephalitis, hemorrhagic stroke, thrombosis of the posterior inferior cerebellar artery. In the last two cases, at the onset of vascular disorders, Horner's syndrome is observed together with severe dizziness and vomiting.

If, in addition to the sympathetic pathway, the nuclei of the V or IX, X pairs of cranial nerves are involved in the pathological process, analgesia, thermoesthesia of the face on the ipsilateral side, or dysphagia with paresis of the soft palate, pharyngeal muscles, and vocal cords will be noted, respectively.

Due to the more central location of the sympathetic pathway in the lateral columns of the spinal cord, the most common causes of damage are cervical syringomyelia, intramedullary spinal tumors (glioma, ependymoma). Clinically, this is manifested by decreased pain sensitivity in the arms, decreased or lost tendon and periosteal reflexes from the arms, and bilateral Horner's syndrome. In such cases, the first thing that attracts attention is ptosis on both sides. The pupils are narrow, symmetrical, with a normal reaction to light.

Horner's syndrome of peripheral origin. The lesion of the first thoracic root is the most common cause of Horner's syndrome. However, it should be noted right away that pathology of the intervertebral discs (hernias, osteochondrosis) rarely manifests itself as Horner's syndrome. The passage of the first thoracic root directly above the pleura of the apex of the lung causes its lesion in malignant diseases. Classic Pancoast syndrome (cancer of the apex of the lung) manifests itself as pain in the armpit, atrophy of the muscles (small) of the arm and Horner's syndrome on the same side. Other causes are neurofibroma of the root, additional cervical ribs, Dejerine-Klumpke paralysis, spontaneous pneumothorax, other diseases of the apex of the lung and pleura.

The sympathetic chain at the cervical level can be damaged as a result of surgical interventions on the larynx, thyroid gland, injuries in the neck area, tumors, especially metastases. Malignant diseases in the area of the jugular foramen at the base of the brain cause various combinations of Horner's syndrome with damage to the IX, X, XI and XII pairs of cranial nerves.

If the fibers of the internal carotid artery plexus are affected above the superior cervical ganglion, Horner's syndrome will be observed, but only without sweating disorders, since the sudomotor pathways to the face are part of the external carotid artery plexus. Conversely, sweating disorders without pupillary disorders will be observed when the fibers of the external carotid plexus are involved. It should be noted that a similar picture (anhidrosis without pupillary disorders) can be observed with damage to the sympathetic chain caudal to the stellate ganglion. This is explained by the fact that the sympathetic pathways to the pupil, passing through the sympathetic trunk, do not descend below the stellate ganglion, while the sudomotor fibers going to the sweat glands of the face leave the sympathetic trunk, starting from the superior cervical ganglion and ending with the superior thoracic sympathetic ganglia.

Trauma, inflammatory or blastomatous processes in the immediate vicinity of the trigeminal (Gasserian) ganglion, as well as syphilitic osteitis, carotid artery aneurysm, alcoholization of the trigeminal ganglion, herpes ophthalmicus are the most common causes of Raeder's syndrome: damage to the first branch of the trigeminal nerve in combination with Horner's syndrome. Sometimes damage to the cranial nerves of the IV, VI pairs is added.

Pourfur du Petit syndrome is a reverse Horner syndrome. In this case, mydriasis, exophthalmos and lagophthalmos are observed. Additional symptoms: increased intraocular pressure, changes in the vessels of the conjunctiva and retina. This syndrome occurs with local action of sympathomimetic agents, rarely with pathological processes in the neck area, when the sympathetic trunk is involved, as well as with irritation of the hypothalamus.

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Special forms of pupillary disorders

This group of syndromes includes cyclic oculomotor palsy, ophthalmoplegic migraine, benign episodic unilateral mydriasis, and tadpole pupil (intermittent segmental dilator spasm lasting several minutes and recurring several times a day).

Argyle-Robertson pupils

Argyle-Robertson pupils are small, unequal in size and irregularly shaped pupils with poor reaction to light in the dark and good reaction to accommodation with convergence (dissociated pupillary reaction). It is necessary to differentiate the Argyle-Robertson symptom (a relatively rare sign) and bilateral tonic pupils of Edie, which are more common.