Tonic Pupil Research Articles

Ross Syndrome with Sweating Anomaly Associated with Sjögren Syndrome: An Infrared Thermo­graphic Case Study

Ross syndrome is a rare partial dysautonomic syndrome of unknown aetiology, characterized by a one-sided or bi-lateral anhidrosis associated with Holmes-Adie syndrome (defined by tonic pupil and hyporeflexia of deep tendons) (1). Since it was first described in 1958 (2), approxima-tely 50 cases have been described in the literature (3). Dermatologists may be confronted with this disorder of thermoregulation, which is often revealed by a segmental “compensatory” hyperhidrosis. We describe here a case of Ross syndrome associated with Sjogren syndrome (SS) and discuss the potential relationship between these two entities. Thermography imaging exploration with an in-frared camera performed in different ambient temperature settings allowed better definition of the thermoregulatory sweating abnormalities in our patient. Moreover, to our knowledge, this examination showed, for the first time, an unexpected body “thermal pattern”, which may be characteristic of Ross syndrome. CASe RepoRTWe present here a case of a 35-year-old woman with a 10-year medical history of localized hyperhidrosis. Her medical history revealed autoimmune thyroid disease and SS. The hyperhidrosis appeared at an ambient tem-perature of approximately 25–27°C and was localized on the left side of her lower back, extending belt-like towards the side and in the controlateral lower back on the right side, as well as on the nape of her neck and shoulders. The rest of the skin was anhidrotic. She was also heat intolerant, with lack of sweating, abnormal increase in body temperature and generalized fati-gability when exposed to high ambient temperatures (32–34°C). Both pupils showed a slow reaction to light and a normal constriction to a near target, and deep tendon jerks were absent without motor deficits (Holmes-Adie syndrome). There were no other signs of autonomic dysfunction. punch biopsies obtained from hyperhidrotic and hypohidrotic skin areas were normal. The skin direct immunofluorescence test was negative. Blood explorations showed an isolated presence of anti-SSA, anti-SSB antibodies and anti-thyroid antibodies. Serum ganglionic (AChR) antibody was negative. Oral and conjunctival Sicca were objectively confirmed by Schirmer’s test. Salivary gland biopsy revealed lympho-cytic infiltration in both periglandular and perivascular regions. All of these Sicca findings fulfilled the diag-nostic criteria for primary SS (4). Brain and spinal cord magnetic resonance imaging (MRI), as well as thoracic and abdominal computed tomography scan findings, were normal. Electrophysiological explorations of both hands and forearms showed an absence or collapse of the sympathetic skin responses. Nerve conduction study findings, EEG and cardiac tilt-test (reflecting the adren-ergic sympathetic and parasympathetic functions) were normal. Thermographic explorations with an infrared camera (A320, FLIRsystems, Inc., Issy Les Moulineaux, France) allowed for evaluating the body’s surface tem-perature at 22°C and after a 20 min exposure to 32°C ambient temperature (Fig. 1). This examination was significantly more efficient than the Minor Starch Test and clearly delimited the skin thermoregulation abnor-malities associated with Ross syndrome. Hyperhidrotic and anhidrotic areas were also clearly visualized as the lowest and highest estimated skin surface temperature. This examination showed large dermatomal-like pat-terns in hyperhidrotic areas (lower back and shoulder regions), but also detected unexpected smaller patch-

Ross syndrome: Unilateral hyperhidrosis, Adie's tonic pupils and diffuse areflexia

Ross syndrome is a rare disorder first described in 1958 with partial autonomic dysfunction. It has three basic components including unilateral or bilateral segmental anhidrosis, Adie's tonic pupils and areflexia or hyporeflexia of deep tendon reflexes. The most disturbing symptom in the patients is segmental compensatory hyperhidrosis and often the hypohidrosis or anhidrosis is not even noticed. While the pathogenesis of Ross syndrome is unclear, degenerative changes or damage to the peripheral autonomic nerve system or dorsal root ganglia have been suggested as possible causes. About 50 cases have been reported, usually by neurologists and ophthalmologists, and less often by dermatologists. We present a 26-year-old patient who displayed the classic triad of this syndrome, emphasizing that the presenting complaint may be hyperhidrosis and that multidisciplinary evaluation in neurology and ophthalmology is essential.

An Unusual Cause of Fulminant Guillain-Barré Syndrome: Angel's Trumpet

A 5-year-old previously healthy boy presented with typical findings of Guillain-Barré syndrome and unilateral tonic pupil. He was placed on mechanical ventilation for 35 days for respiratory failure. Plasmapheresis and two courses of intravenous immunoglobulin therapy were given to the patient, and he experienced stepwise recovery from his illness. This case of acute motor axonal neuropathy type Guillain-Barré syndrome is novel in that the cause was established as ingestion of a toxic solanaceous plant, angel's trumpet (Brugmansia suaveolens; syn. Datura suaveolens). Understanding the signs and symptoms of angel's trumpet toxicity can allow for early diagnosis and proper case management.

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.

Ciliary ganglioplegic migraine: Migraine-related prolonged mydriasis

Transient, unilateral mydriasis has been reported in migraine patients, and this has been regarded as a possible co-morbidity between migraine and Adie's tonic pupil. Mydriasis that outlasts the duration of migraine attacks is rare. Through an eight-year period we have studied all patients referred to our neurological clinic because of migraine attack with mydriasis. All the patients underwent thorough neurologic and ophthalmologic examinations including MRI of the brain and testing of the pupil response to ocular instillation of dilute pilocarpine (0.125%). Seven women and two men, with a mean age of 33.8 ± 12.3 years (range: 19-52) were included. The patients presented during one hemicranial migraine attack with an ipsilateral mydriasis that persisted for a mean of three months, while migraine headaches remained with their typical episodic course. In all the patients a cholinergic supersensitivity in the symptomatic pupil was demonstrated, thus pointing to a dysfunction of the ipsilateral ganglionic parasympathetic fibers. Synchronous co-localization of the features suggests a pathogenic link between the pupil dysfunction and migraine, rather than a simultaneous coexistence of two independent disorders. Likely explanations include a latent Adie's pupil that could have been triggered during a particular migraine attack; a ciliar ganglionic lesion/dysfunction produced by the migrainous process; an ophthalmoplegic migraine with selective parasympathycoparesis; or an episodic ciliar ganglionitis with migrainous features. Ciliary ganglioplegic migraine is proposed as a nominal term pointing to the possible anatomic source of the migrainous-related pupil dysfunction; the pathogenesis remains unknown.

The effect of controlled photopigment excitations on pupil aperture

In addition to rods and cones, the human retina contains melanopsin which has been identified recently in the body and dendrites of a few ganglion cells. The intrinsically photosensitive retinal ganglion cells (ipRGCs) are good candidates for controlling the tonic pupil aperture but their spectral sensitivity is close to those of rods and S-cones which are other candidates. Our study aims at identifying the stimulus for the pupil response when the luminance is constant and the spectrum of the light changes. A light booth was equipped with five types of coloured light emitting diodes (LEDs): Blue, Cyan, Green, Orange and Red. The intensity of each LED type could be adjusted to control the light spectrum. Illumination pairs were prepared ensuring the exclusive variation of excitation of one receptor type and silent substitution for others. Because the range of the possible controlled changes of excitation was narrow, we also prepared illumination pairs ensuring silent substitution for luminance rather than for L-cones and M-cones independently. Photographs of the observer's eyes were taken following one minute of adaptation to each illumination and the ratio of pupil to iris diameter was measured. No differential pupillary response was observed with a variation of rod, melanopsin or S-cone excitation alone. A differential pupillary response could only be obtained with a variation of the melanopsin stimulus of sufficient high contrast with or without a concurrent variation of rods.

Bilateral Holmes–Adie syndrome as an early manifestation of the HIV neuropathy

A 38-year-old HIV-1 infected woman affected with bilateral tonic pupils. Ophthalmologic examination confirmed Holmes-Adie syndrome (HAS), and peripheral distal polyneuropathy, orthostatic hypotension and leg hyperhidrosis were detected on further workup. The HAS can be either idiopathic or associated with neuropathy of various etiology (autoimmune, paraneoplastic and infectious). In our patient, the pupillotonia was the first and early symptom of hitherto unrecognized HIV neuropathy. HAS has been previously observed in association with syphilis, Lyme borreliosis, herpes simplex and parvovirus B19 infection. Our case is the first report of HAS in a case of HIV infection.

Friederich Nietzsche and the seduction of Occam’s razor

Friedrich Nietzsche developed dementia at the age of 44 years. It is generally assumed that the cause of his dementia was neurosyphilis or general pareisis of the insane (GPI). Others have proposed frontal-based meningioma as the underlying cause. We have reviewed Nietzsche's medical history and evaluated the evidence from the medical examinations he underwent by various physicians. We have viewed the possible diagnosis of GPI or meningioma in light of present neuro-ophthalmic understanding and found that Nietzsche did not have the neurological or neuro-ophthalmic symptoms consistent with a diagnosis of GPI. The anisocoria which was assumed to be Argyll Robertson pupil was present since he was six years of age. He did not have tongue tremor, lacked progressive motor features and lived at least 12 years following the onset of his neurological signs. Furthermore, the headaches that have been attributed to a frontal-based tumour were present since childhood and the pupil abnormality that has been interpreted as an "afferent pupillary defect" had the characteristics of an abnormality of the efferent pupillary innervation. None of the medical records or photographs suggest there was any ocular misalignment. We concluded that neither diagnosis of GPI nor frontal-based meningioma is convincing. It is likely that Nietzsche suffered from migraines, his blindness in his right eye was a consequence of high progressive myopia associated with retinal degeneration, his anisocoria explained by unilateral tonic pupil, and his dementia by an underlying psychiatric disease.

Bowel obstruction and urinary retention in a 22-year-old: Beware the tonic pupil

Bowel obstruction and urinary retention in a 22-year-old: Beware the tonic pupil

Early Dorsal Midbrain Syndrome Mimicking an Adie's Tonic Pupil

BackgroundWhile tonic pupils have been attributed to various diseases, including syphilis, herpes zoster, orbital trauma, temporal arteritis, endometriosis, and paraneoplastic syndromes, obstructive hydrocephalus has not been implicated.Case ReportA 36-year-old woman visited a neurology department with a 7-day history of throbbing headache and blurred vision in both eyes. She had early dorsal midbrain syndrome mimicking an Adie's tonic pupil, and cholinergic supersensitivity was demonstrated using topical 0.125% pilocarpine. Brain MRI revealed obstructive hydrocephalus at the level of the aqueduct of Sylvius, and her symptoms resolved 4 days after surgery.ConclusionsWe report a patient with early dorsal midbrain syndrome that was initially believed to represent a tonic pupil on the basis of pharmacologic testing. The findings in our patient suggested that early dorsal midbrain syndrome mimicking an Adie's tonic pupil can be caused by obstructive hydrocephalus compressing the Edinger-Westphal nucleus.

Bilateral Tonic Pupil Secondary to Migraine in a Child

Bilateral idiopathic tonic pupil is characterized by enlarged pupils, poor response to light and accommodation, strong and tonic response to near stimuli, vermiform movements of the iris on slit-lamp examination, and cholinergic supersensitivity. The authors present a case of a 10-year-old girl who was referred with abnormal pupils and complained of headaches. After ophthalmological and neurological examination, she was diagnosed as having migraine and secondary idiopathic bilateral tonic pupils. To the authors' knowledge, this is the first case of a child with bilateral Adie's pupil secondary to migraine to be reported.

Ross syndrome with ANA positivity: A clue to possible autoimmune origin and treatment with intravenous immunoglobulin

A 28-year-old serving soldier presented with patchy areas of absence of sweating and blurring of vision. On examination he was found to have segmental anhidrosis, right sided tonic pupil and absent ankle jerks. Investigations revealed ANA positivity with no other abnormalities. He was treated with Intravenous immunoglobulin. This case of Ross syndrome is reported for its rarity as well as a clue to its probable autoimmune origin and treatment option with intravenous immunoglobulins.

Neurosyphilis With Unilateral Optic Tract Lesion Causing Homonymous Hemianopia

Homonymous hemianopia is not a rare symptom. Many causative lesions and pathologies are known, although a unilateral optic tract lesion caused by syphilis is rare. A 56-year-old woman developed a congruous right homonymous hemianopia and bilateral tonic pupils with irregular shape. Brain T2-weighted and fluid attenuated inversion recovery magnetic resonance imaging (MRI) revealed a spindle-like high-intensity lesion in her left postchiasmal optic tract. The rim of this lesion enhanced with gadolinium without meningeal enhancement. Serum and cerebrospinal fluid venereal disease research laboratory tests were positive. Cerebrospinal fluid contained 71 white blood cells/microL (mononuclear cells = 97%) and 48 mg/dL of protein. The hemianopia disappeared after administration of benzylpenicillin. Neurosyphilis should be added to the list of differential diagnoses for an isolated optic tract lesion.

Residual and Persistent Adie's Pupil After Pediatric Ophthalmoplegic Migraine

We report on a 9-year-old girl diagnosed with ophthalmoplegic migraines who had been previously diagnosed, at age 7 years, with typical migraines with aura. After resolution of the third ophthalmoplegic migraine attack, the only evident residual clinical sign was Adie's pupil. During 24-month follow-up, at age 11 years, a neurologic examination produced completely normal results. However, Adie's pupil persisted. Adie's tonic pupil can be associated with extraocular diseases, which were all excluded in this patient. The mechanisms underlying tonic pupil are not fully understood. This is the first report, to the best of our knowledge, of an ophthalmoplegic migraine followed by persistent Adie's pupil. Possible pathogenic mechanisms are discussed.

Charcot–Marie–Tooth disease type 2J with MPZ Thr124Met mutation: clinico-electrophysiological and MRI study of a family

The purpose of the present study was to describe clinico-electrophysiological features and lower limb muscle MRI findings in a CMT2J pedigree due to MPZ Thr124Met mutation. We examined the proband, aged 56 years, and her affected daughter and son, aged 30 and 29 years. Disease severity in terms of ability to walk and run was established using a nine-point functional disability scale (FDS). We administered the CMT neuropathy score (CMTNS) based on patient's symptoms, neurologic examination and neurophysiologic testing. All three patients had non-symptomatic Adie's pupil. The proband and her son presented with late-onset lower limb sensorimotor neuropathy and pes cavus; the proband's daughter had no signs of polyneuropathy. FDS score was 4 in the proband, 2 in her son, and 0 (normal) in her daughter. In both symptomatic patients, electrophysiological study showed a pattern of length-dependent axonal neuropathy mainly involving lower limb nerves; this was normal in the other patient. CMTNS was 18 in the proband, 12 in her son, and 0 (normal) in her daughter. MRI of foot and leg musculature was normal in the proband's daughter, whereas the other two patients showed massive fatty atrophy of intrinsic foot musculature, extensive and diffuse fatty atrophy of leg muscles in the proband, and mild distally accentuated fatty infiltration of calf muscles in her son. Muscle edema, detected only in the proband's son, was present in 7 out of 22 (33%) of visualized leg muscles, whereas contrast enhancement occurred in 6 of them. The reported mutation may manifest with either isolated Adie's pupil or pupil abnormalities with late-onset sensorimotor length-dependent axonal polyneuropathy, though the presence of pes cavus might indicate an earlier onset. MRI examination helps to delineate an accurate extent of muscle involvement in the disease.

Neurological problems presenting to an ophthalmic casualty department

All patients presenting with neurological problems to an eye hospital casualty department over one year were prospectively studied. A total of 119 patients were identified. The most frequent diagnoses were retrobulbar neuritis (34; 28.5%), sixth cranial nerve palsy (22; 18.5%), third cranial nerve palsy (15; 12.6%) and Adie's tonic pupil (11; 9%). Cranial nerve palsies were most commonly due to diabetes or hypertension (16; 43.2%). Only one intracranial aneurysm was found. Symptoms included blurred vision (52; 43.7%), binocular diplopia (51; 42.8%), and eye pain (27; 22.7%). Fifty patients (42.0%) were referred by a general medical practitioner. Twenty-two (18.5%) were admitted to hospital. Forty-nine skull X-rays were requested and all were normal. Twenty-nine chest X-rays were requested. One (3.4%) showed an abnormality (carcinoma of the bronchus). Neurological patients present to ophthalmic casualty departments because of ophthalmic symptoms. Ophthalmic casualty officers are able to make working diagnoses and to direct patients appropriately. The use of investigations in the casualty department, however, is unlikely to be productive.

Bilateral internal ophthalmoplegia as an initial sole manifestation of Miller Fisher syndrome

Although there have been reports regarding the frequent involvement of the pupils in Miller Fisher syndrome (MFS) and related syndromes, internal ophthalmoplegia has not been described as the initial sole manifestation of typical MFS. Recently, we encountered a woman with MFS whose initial manifestation was blurred vision because of bilateral tonic pupils. Investigations, including brain imaging, cerebrospinal fluid examination and nerve conduction studies were normal except for elevated serum levels of immunoglobulin G anti-GQ1b antibody. During the disease, she subsequently developed bilateral sixth and seventh nerve palsies, gait ataxia, and areflexia. We treated her with intravenous immunoglobulin and she showed a stepwise recovery from her illness. This case suggests that bilateral internal ophthalmoplegia can be a preceding sole manifestation of typical MFS.

RESOLUTION OF MYDRIATIC PUPIL AFTER ANGIOPLASTY AND STENTING OF CERVICAL INTERNAL CAROTID ARTERY DISSECTION

A patient with cervical internal carotid artery (ICA) dissection presented with visual loss and a mydriatic pupil that resolved after angioplasty and stenting. A 49-year-old woman presented with a unilateral dilated tonic pupil and transient monocular visual loss and subsequently developed speech disturbance. Angiography revealed a left cervical ICA dissection with significant luminal narrowing. The ophthalmic artery filled retrograde through external carotid artery branches and reconstituted the supraclinoid ICA. Computed tomographic perfusion showed significant hypoperfusion of the left hemisphere. Magnetic resonance imaging showed punctate boundary zone infarcts. The patient experienced pressure-dependent left hemispheric transient ischemic attacks and pressure-dependent ocular findings despite anticoagulation. She underwent uncomplicated left ICA angioplasty and stenting. The flow through the ophthalmic artery became anterograde. The tonic pupil returned to symmetry with the contralateral pupil, and the patient's symptoms resolved completely. Cervical ICA dissection can manifest with a tonic mydriatic pupil. Treatment with angioplasty and stenting of the dissected segment can restore flow and resolve the pupillary abnormality. A pathophysiological mechanism for the mydriasis is proposed.

Hereditary motor and sensory neuropathy type 1 (HMSN1) associated with cranial neuropathy: an autopsy case report

A family with hereditary motor and sensory neuropathy type 1 (HMSN1) is reported. Three patients suffered only pupillary abnormality, two patients showed Adie's syndrome and peripheral neuropathy, and one had cranial neuropathy. Adie's syndrome and severe peripheral neuropathy. Autopsy of the latter revealed reduction of myelinated nerve fibers in the trigeminal, facial and hypoglossal nerves. There was extensive degeneration of the posterior column of the spinal cord. At the anterior horns, loss of motor neurons was observed, particularly at the lumbar level. The anterior and posterior roots showed loss of myelinated fibers. HMSN1 is only rarely associated with cranial neuropathy, and this is probably the first autopsy-proved case.

A new clinical sign in Holmes-Adie syndrome

A new clinical sign in Holmes-Adie syndrome