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.

[Clinical presentations of Ross syndrome have changed in their lateralities following the anteriotemporal lobectomy for refractory focal epilepsy].

We describe a 60-year-old woman with medically refractory left mesial temporal lobe epilepsy accompanied by Ross syndrome. The patient had a partial triad of Ross syndrome with hypohydrosis only on her right side (contralateral to the epileptic seizure focus), Adie's tonic pupil on the right, and areflexia while her seizures used to be medically refractory. However, her hypohidrosis and Adie's tonic pupil have completely changed in terms of laterality following nearly complete seizure freedom resutling from left temporal lobectomy. This unique change in laterality in Ross syndrome is most likely caused by remote effects of the near-absent epileptic acitivity, and it also may contribute to understanding the pathophysiological mechanism of Ross syndrome.

Absent cardiac and muscle sympathetic nerve activities involvement in Ross syndrome: A follow-up study.

PURPOSE: Ross syndrome (RS) is characterized by selective involvement of post-ganglionic skin sympathetic nerve fibres. We report a follow-up study in 4 patients to clarify whether in RS autonomic dysfunction spreads affecting also cardiovascular system. METHODS: The patients underwent cardiovascular reflexes (CVR) and microneurography recording of muscle sympathetic nerve activity (MSNA) for a follow-up mean period of 5years. RESULTS: CVR and MSNA were normal at baseline and unchanged over the follow-up. CONCLUSIONS: Cardiovascular autonomic system is spared in RS differently from skin autonomic activity dysfunction which progress over time. However, before drawing any definite conclusion, a large cohort of patients needs to be studied.

Muscle and skin sympathetic activities in Ross syndrome.

OBJECTIVES: Ross syndrome (RS) is a rare degenerative disorder characterized by tonic pupil, areflexia and anhydrosis. The underlying lesion affects postganglionic skin sympathetic nerve fibers whereas the postganglionic muscle sympathetic branch is thought to be spared. Microneurography explores both skin and muscle peripheral sympathetic branches and it does not usually detect peripheral sympathetic outflow in either branch in chronic autonomic failure syndromes. The aim of this study was to record sympathetic activity by microneurography for the first time in RS patients to confirm the selective involvement of skin sympathetic nerve activity (SSNA) with spared muscle sympathetic nerve activity (MSNA). METHODS: We studied seven patients (49 ± 14 years, four males) with a typical clinical picture and skin biopsy findings. Patients underwent cardiovascular reflexes and microneurography from the peroneal nerve (anhydrotic skin) to record MSNA, SSNA and the corresponding organ effector responses (skin sympathetic response-SSR and skin vasomotor response-SVR) in the same innervation field. The absence of sympathetic bursts was established after exploring at least three different corresponding nerve fascicles. Twenty age-matched healthy subjects served as controls. RESULTS: RS patients complained of diffuse anhydrosis and they showed tonic pupil and areflexia. Cardiovascular reflexes were normal. All patients displayed absent SSNA, SSR and SVR whereas MSNA was always recorded showing normal characteristics. CONCLUSION: Microneurographic study of sympathetic activity from affected skin confirmed the selective involvement of skin sympathetic activity with spared muscle sympathetic activity and it may represent the neurophysiological hallmark of the disease. SIGNIFICANCE: Microneurography together with clinical and skin biopsy findings may contribute to RS diagnosis. Our data also suggest that autonomic damage in RS does not involve cardiovascular activity.

[Pupillary disorders - diagnosis, diseases, consequences]. / Pupillenstörungen - Diagnostik, Erkrankungen, Konsequenz.

Examination of the pupil offers an objective evaluation of visual function as well as the vegetative pathways to the eye. Essential information is gathered within a short time. This makes pupillary inspection a valuable part of the routine ophthalmological, neurological and general medical examinations. Due to the proximity of pupillary pathways to various anatomic structures, pupillary dysfunction can be caused by a variety of disorders, some of which may be life threatening. The ophthalmologist plays a key role in detecting pupillary disorders and in directing further investigations. Therefore, one should have a good knowledge of the diagnostic significance of pupillary function and dysfunction.

[Unilateral dilated light-unresponsive pupil in Guillain Barré syndrome]. / Dilateret og lysstiv pupil ved Guillain-Barrés syndrom.

We report a case of Guillain Barré syndrome presenting with a unilateral internal ophthalmoplegia and unilateral minor sensory impairment, followed by respiratory failure, missing reflexes, tetraparesis and bilateral facial weakness. All symptoms responded to immunoglobulin. The diagnosis was confirmed by cerebrospinal fluid analysis and electroneurography. This case was especially unusual because the pupil abnormality was unilateral and appeared prior to motor impairment.

Mydriatic pupil in giant cell arteritis.

A mydriatic pupil has been infrequently reported as a manifestation of giant cell arteritis. We report a patient with acute, evolving pupil dilation who was diagnosed with biopsy-proven giant cell arteritis. We document the time course for the development of pupillary near-light dissociation and denervation hypersensitivity. We discuss the possible mechanisms leading to mydriasis, including 1) parasympathetic dysfunction due to ischemia of the ciliary ganglion and post-ganglionic parasympathetic fibers and 2) direct iris ischemia. Repeated episodes of pupil dilation in this patient suggested ongoing microvascular insufficiency.

Ross syndrome associated with cytomegalovirus infection.

We report a 40-year-old woman who developed Ross syndrome (impairment of sweating and thermoregulation, tonic pupils, and hyporeflexia) associated with cytomegalovirus (CMV) infection. Her serum CMV IgM and IgG antibody titer levels were elevated. Along with clinical improvement, a gradual decrease of her elevated CMV IgM antibody titer level was seen with a continued increase in her CMV IgG antibody titer level. The CMV IgM antibody titer was also positive in the cerebrospinal fluid.

Isolated generalised anhidrosis induced by postganglionic sympathetic skin nerve fibre degeneration: an incomplete Ross syndrome?

Ross syndrome is characterised by tonic pupil, areflexia and anhidrosis, and the underlying lesion affects postganglionic skin sympathetic nerve fibres. We describe a 51-year-old man who had complained of anhidrosis since adolescence, at which time this problem was limited to the lower arms. The thermoregulatory sweating test disclosed generalised anhidrosis (GA) except for two small skin areas that were located in the right palm and left neck. Immunofluorescence analysis disclosed no cholinergic sudomotor fibres around the sweat glands of non-sweating skin areas, which were evident although sparse and deranged in the sweating site. In our patient, GA was induced by degeneration of postganglionic sympathetic skin nerve fibres, as found in Ross syndrome, although his clinical picture was incomplete as it lacked tonic pupil and areflexia. Isolated GA induced by degeneration of postganglionic sympathetic nerve fibers, directly evaluated by skin biopsy, has not previously been described.

Reversible tonic pupils.

A 36-year-old man with a remote history of Hodgkin lymphoma and a recent history of non-Hodgkin lymphoma (NHL) developed tonic pupils and absent deep tendon reflexes in the lower extremities. One year later, pupils were normal except for slight iris segmental contraction to light. Over the next 2 years, the patient remained asymptomatic, and pupils remained unchanged. The NHL went into remission, and no other neurologic manifestations appeared. This is the first report of reversible tonic pupils. They may have a pathogenesis different from that typically seen in irreversible tonic pupils.

The dilated pupil: an update.

The dilated pupil can present a significant challenge to the clinician. Although in most cases a complete history and physical examination is sufficient to make an accurate diagnosis, selected patients will require further investigation, including pharmacologic testing and neuroimaging. This review outlines the physiology, clinical features, and diagnostic approach to the most important causes of the dilated pupil. Particular attention is given to recent publications on this topic.

Bilateral tonic pupils: Holmes Adie syndrome or generalised neuropathy?

AIM: To compare the pupil signs in patients with bilateral pupillotonia caused by Holmes-Adie syndrome or generalised peripheral neuropathy. METHODS: Infrared video pupillographic techniques were used to measure a number of pupil variables in patients with Holmes-Adie syndrome, generalised neuropathy (various aetiologies) and healthy age-matched control subjects. RESULTS: Regardless of aetiology, the patients generally had pupil signs typical of pupillotonia (small dark diameters, large light diameters, tonic near responses, attenuated light responses with light-near dissociation, and sector palsy). However, significant differences were found in the prevalence and magnitude of several pupil variables in the two patient groups. In particular, sector palsy and anisocoria exceeding 1 mm (in the light) were seen much more commonly in Holmes-Adie patients than patients with generalised neuropathy. The presence of both these pupil signs can be used to distinguish between these diagnoses with a sensitivity of 58% and a specificity of 90%. CONCLUSIONS: The tonic pupils of patients with Holmes-Adie syndrome are significantly different to those found in patients with generalised neuropathy; recognition of these differences may allow distinction between these diagnoses.

Ross syndrome: a rare or a misknown disorder of thermoregulation? A skin innervation study on 12 subjects.

Ross syndrome is described as a rare disorder of sweating associated with areflexia and tonic pupil. Since Ross's first description in 1958, approximately 40 cases have been described. We assessed the involvement of cutaneous innervation in 12 subjects with Ross syndrome using quantitative sensory testing, sweating assessment and immunohistochemical study of anhidrotic and hyperhidrotic skin. This evaluation was repeated over time in 4 out of 12 subjects. In addition, we enrolled four subjects with Holmes-Adie syndrome (areflexia and tonic pupil) to investigate similarities between the two conditions. We found in Ross patients a complex and progressive involvement of cutaneous sensory and autonomic innervation underlying the impairment of heat production and heat dissipation through both loss of sweating and loss of cutaneous blood flow regulation. In Holmes-Adie subjects we found a mild impairment of sweating without thermoregulatory problems. The persistence of a sudomotor vasoactive intestinal peptide-immunoreactive (VIP-ir) innervation, although deranged and poor, definitely differentiated Holmes-Adie from Ross patients. Ross syndrome is a progressive and complex disorder of thermoregulation difficult to differentiate from the probably pathogenetically related Holmes-Adie syndrome. Sweating assessment and skin biopsy are suitable tools to define a boundary between them. Owing to the large number of Ross patients observed in only 5 years, and to the long and complex medical history of most of them, doubts arise on the effective rarity of this condition, and we warn family doctors and other specialists, besides neurologists, to become aware of this complex disorder.

Adie's pupils in paraneoplastic ganglionopathy with ANNA-1.

Autonomic disturbances are common in patients with paraneoplastic syndromes associated with type-1 antineuronal nuclear autoantibodies (ANNA-1), although pupillary disturbances are infrequent. The authors describe a patient with ANNA-1 associated paraneoplastic sensory neuronopathy and bilateral Adie's pupils.

Ross syndrome, an entity included within the spectrum of partial disautonomic syndromes.

Ross syndrome is a degenerative peripheral nervous system disorder defined by the following triad: unilateral or bilateral segmental anhidrosis, hyporeflexia of deep tendon reflexes and Adie's tonic pupils. The most disturbing symptom is segmental compensatory hyperhidrosis. It has only occasionally been reported in the dermatological literature. We present a 35-year-old woman with chronic hepatitis C who developed the characteristic triad of Ross syndrome within 1 month. The patient was otherwise healthy except for an aneurysm of the left medium brain artery not responsible for the syndrome.

Neuro-ophthalmologic and electroretinographic findings in pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome).

PURPOSE: The onset of pantothenate kinase-associated neurodegeneration (PKAN) occurs in the first and second decade of life and a pigmentary retinal degeneration is a feature of the disorder. Since the neuro-ophthalmologic and electroretinographic (ERG) features have never been well delineated, we describe them in 16 patients with PKAN. DESIGN: Observational case series. METHODS: Sixteen patients with genetic and neuroimaging-confirmed PKAN were examined. Ten underwent neuro-ophthalmologic examination and all had ERGs. RESULTS: Of the 10 who underwent neuro-ophthalmologic examination, all showed saccadic pursuits and eight showed hypometric or slowed vertical saccades. Seven of eight had inability to suppress the vestibulo-ocular reflex; two patients could not cooperate. Two had square wave jerks and four had poor convergence. Vertical optokinetic responses were abnormal in five, and two patients had blepharospasm. Eight patients had sectoral iris paralysis and partial loss of the pupillary ruff consistent with Adie's pupils in both eyes. Only four of 10 examined patients showed a pigmentary retinopathy, but 11 of 16 had abnormal ERGs ranging from mild cone abnormalities to severe rod-cone dysfunction. No patient had optic atrophy. The PANK2 mutations of all of the patients were heterogeneous. CONCLUSIONS: Adie's-like pupils, abnormal vertical saccades, and saccadic pursuits were very common. These findings suggest that mid-brain degeneration occurs in PKAN more frequently than previously thought. ERG abnormalities were present in approximately 70% and no patient had optic atrophy. Although genotype-ocular phenotype correlations could not be established, allelic differences probably contributed to the variable clinical expression of retinopathy and other clinical characteristics in these patients.