Adie's Pupil: A Diagnostic Challenge for the Physician.

Adie's pupil, also called tonic pupil, is mainly seen in young women. Most patients have unilateral eye involvement. The pupil of the affected side is significantly larger than that on the healthy side. The direct and indirect light reflection from the pupil on the affected side disappears. The pupil on the affected side is sensitive to low concentrations of pilocarpine. The pathogeneses of Adie's pupil are complex, some of which are insidious and lack corresponding specific diseases. Through a literature review, we found that Adie's pupil is mainly associated with infectious diseases, most commonly syphilis, followed by immune diseases and paraneoplastic syndromes. The ophthalmological symptoms and pupil abnormalities can disappear after active treatment of the primary disease. Pilocarpine can be used to treat ophthalmologic symptoms, such as blurred vision, for which patients might visit an ophthalmologist or neurologist. It is essential for clinicians to improve their understanding of the disease to avoid misdiagnosis. Differential diagnosis between Adie's pupil, oculomotor nerve palsy, anticholinergic drug overdose, Argyll-Robertson pupil, and congenital mydriasis need to be identified by the physician. Here, the clinical manifestations, pathogenesis, relationship between Adie's pupil and diseases, and differential diagnosis of Adie's pupil are reviewed.

Dilute pilocarpine test for diagnosis of Adie's tonic pupil.

We have compared the diagnostic ability of different concentrations of 0.125% and 0.0625% dilute pilocarpine for detecting denervation supersensitivity in unilateral Adie's tonic pupil. This retrospective, observational, case-control study involved 117 subjects, consisting of 56 patients with unilateral Adie's tonic pupil and 61 controls with other causes of unilateral dilated pupils. Subjects underwent the dilute pilocarpine test with one of the two concentrations, 0.125% or 0.0625%. Pupillary light reflex was recorded with a dynamic pupillometer at baseline and at 30-40 min after instilling one of the two concentrations of dilute pilocarpine. Diagnostic accuracy of two different concentrations of the dilute pilocarpine test, 0.125% group versus 0.0625% group, were compared by area under the receiver operating characteristic curve (AUC). Diagnostic ability of the dilute pilocarpine test for detecting denervation supersensitivity in unilateral Adie's tonic pupil was significantly better in the 0.0625% group than in the 0.125% group (AUC = 0.954 vs. 0.840, respectively, P = 0.047). In the 0.0625% group, the change in maximal pupil diameter of ≥ 0.5 mm after topical pilocarpine instillation showed 100% sensitivity and 82.8% specificity for detecting Adie's tonic pupil. This study confirmed that pupillary constriction with 0.0625% pilocarpine is better than 0.125% pilocarpine for detecting denervation supersensitivity in Adie's tonic pupil. Digital pupillometry is a reliable method for assessing denervation supersensitivity in Adie's tonic pupil.

Progression of cardiovascular autonomic dysfunction in Holmes-Adie syndrome.

The Holmes-Adie Syndrome (HAS) is a disorder of unknown aetiology comprising unilateral or bilateral tonic pupils with near light dissociation and tendon areflexia. Although considered to be benign, troublesome symptoms may result from autonomic disturbances, affecting vasomotor, sudomotor and respiratory function. It is unclear if the autonomic manifestations of the disease remain stable or progress, as longitudinal studies with detailed autonomic assessments have not been described. The authors report four HAS patients studied at intervals over 16, 8, 4 and 2 years with cardiovascular autonomic tests (head-up tilt, isometric exercise, mental arithmetic, cutaneous cold, deep breathing, Valsalva manoeuvre and standing). In each, there was progression of cardiovascular autonomic deficits with time, accompanied by symptomatic worsening. These observations in HAS, for the first time, indicate progression of cardiovascular autonomic dysfunction of clinical significance. This has a number of implications, including those relating to aetiology and prognosis. The authors recommend regular clinical and laboratory follow-up, especially of cardiovascular autonomic function, in patients with HAS.

Holmes-Adie syndrome associated with high altitude pulmonary edema and low chemo-responsiveness to hypoxia.

A 63-year-old patient with Holmes-Adie syndrome presented an altered peripheral chemoreflex and suffered from high altitude pulmonary edema, suggesting an alteration of sensitive afferent fibers from the peripheral chemoreceptors. Chemo-responsiveness to hypoxia should be explored before any exposure to moderate altitude in Holmes-Adie patients.

Idiopathic unilateral hyperhidrosis with Holmes-Adie syndrome: case report.

Hyperhidrosis is a disease that is characterized by excessive sweating due to hyperactivation of eccrine sweat glands. It may be localized or generalized form. Holmes-Adie syndrome is an idiopathic disease with unilateral pupil dilatation and loss of deep tendon reflexes. We present a 37-year-old female patient diagnosed with unilateral hyperhidrosis coincident with Holmes-Adie syndrome because of this unusual presentation.

The Holmes-Adie plus syndrome.

A clinical syndrome of tonic pupil associated with tendon areflexia was first described by Holmes and Adie; autonomic neuropathy and peripheral neuropathy can be associated. The postulated mechanism of areflexia in Holmes-Adie syndrome is a synaptic disorder of the spinal reflex pathways. We report a case of a Holmes-Adie syndrome variant with hitherto unreported cranial neuropathy. A 41 year old woman developed insidious onset of sensory symptoms related to her left trigeminal and chorda tympani nerves over a few months. Physical examination showed generalised tendon areflexia and a left sided Adie's pupil. Imaging did not reveal any structural abnormality. Electrophysiological studies demonstrated an absent blink reflex on stimulating the left supraorbital and infraorbital nerves. These findings were suggestive of a dysfunction affecting the brain stem reflex arc. The pathophysiological process of Holmes-Adie syndrome may be more widespread than previously thought.

Neurophysiological evaluation of areflexia in Holmes-Adie syndrome.

PURPOSE: To evaluate ankle areflexia in Holmes-Adie syndrome (HAS). PATIENTS AND METHODS: Hoffmann (H) and Tendon (T) soleus reflexes, tonic vibration reflex (TVR), and polysynaptic extension reflex of soleus muscle (PERS) were evaluated in eight patients with idiopathic HAS. Motor (MNCV) and sensory (SNCV) nerve conduction velocities, compound motor-action potential (CMAP), and sensory action potential (SAP) were also determined in upper and lower limbs. RESULTS: Soleus T reflex was obtained in one out of eight patients, and H-reflex was found in none of the patients. TVR was recorded in four out of eight patients, and PERS in all of the patients. MNCV, SNCV, CMAP and SAP showed normal values in all patients. In six out of the eight patients a late response following the tibial nerve stimulation showed constant latency, amplitude and morphology, with no recovery cycle or vibration inhibition. CONCLUSION: In this study, the neurophysiological spinal reflex circuitry evaluations support the view that HAS ankles areflexia is due to a selective impairement of monosynaptic connections of Ia afferents. A normal nuclear excitability is suggested by polysynaptic activation of the soleus motor nucleus.

Chronic cough in the Holmes-Adie syndrome: association in five cases with autonomic dysfunction.

The Holmes-Adie syndrome consists of unilateral or bilateral tonic pupils with near light dissociation and tendon areflexia. It is associated with autonomic disturbances affecting sudomotor and vasomotor function. Five such patients are reported on who also had a troublesome chronic dry cough, which was of unknown aetiology and was resistant to a range of treatments. The cough may be related to involvement of afferent or efferent pathways in the vagus. Chronic cough may be an accompaniment in the Holmes-Adie syndrome, like other forms of autonomic dysfunction.

Comparison of cholinergic supersensitivity in third nerve palsy and Adie's syndrome.

OBJECTIVE: To determine whether the degree of cholinergic supersensitivity of the pupil differs in patients with preganglionic injury of the oculomotor nerve (third nerve palsy) compared with patients with postganglionic injury (Adie's pupil). METHODS: In this retrospective study, the authors first identified 11 patients with oculomotor nerve palsy and 11 patients with unilateral Adie's pupil who demonstrated supersensitive pupillary responses using dilute pilocarpine. The same methods for testing supersensitivity of the iris sphincter, and for defining its presence, had been used in both groups of patients. Pupil diameters of the affected and unaffected fellow eye were measured directly from self-developing photographs obtained before and 30 minutes after pilocarpine 0.1% was applied to both eyes. The amount of absolute constriction of the affected pupil, as well as the net constriction of the affected pupil (i.e., the amount of pilocarpine-induced constriction of the unaffected pupil subtracted from the amount of pilocarpine-induced constriction of the affected pupil), was compared between the two groups of patients using the Mann-Whitney test. RESULTS: No significant differences were identified in any of the comparisons. CONCLUSIONS: The degree of cholinergic supersensitivity of the iris sphincter appears to be similar regardless of whether the site of injury along the parasympathetic pathway of the oculomotor nerve is preganglionic or postganglionic.