Argyll Robertson Pupil Research Articles

Diagnosing Tabes Dorsalis in HIV-Negative Patients: Clinical Features, Neuroimaging, and Laboratory Insights in the Modern Antibiotic Era.

Tabes dorsalis is a late manifestation of neurosyphilis, characterized by progressive ataxia, lightning pains, loss of proprioception, and urinary incontinence. The absence of a definitive diagnostic standard and the non-specific clinical manifestations have led to a significant rate of misdiagnoses. Hospitalized patients with tabes dorsalis at Peking Union Medical College Hospital between January 2010 and December 2023 were reviewed. A total of 13 patients were included, with 10 males and 3 females. The median age was 50 years (range, 34-64). The most frequent initial symptoms were limb numbness (30.8%) and lightning pains (30.8%). Eleven patients (84.6%) received misdiagnoses prior to the final diagnosis. The most frequently observed physical sign was positive Romberg's sign (84.6%). Notably, Argyll Robertson pupil was presented in 7 subjects (53.8%). Serological tests revealed positive rapid plasma regain (RPR) and Treponema pallidum particle agglutination (TPPA) for all patients. All CSF samples were TPPA-reactive. Intramedullary hyperintensity on T2-weighted imaging of spinal MRI was found in 5 patients (38.5%). All patients received anti-syphilitic treatment, with effective treatment recorded in five cases. This study underscores the importance of neurological symptoms and signs in diagnosing tabes dorsalis. Individuals with progressive ataxia and positive Romberg's sign should be closely monitored for potential neurosyphilis. Integrating clinical features, laboratory tests, and neuroimaging could reduce misdiagnosis and expedite the initiation of anti-syphilitic therapy.

Teaching NeuroImage: Rapid Identification of Infectious Optic Neuritis by Next-Generation Sequencing.

A 52-year-old, HIV-negative woman presented with one year of bilateral painless central vision loss that worsened over 3 months. A medical examination revealed Argyll Robertson pupil (i.e., accommodates but does not react to light). Single-read next-generation sequencing (NGS) of the CSF identified 89 sequence reads corresponding to Treponema, elevated CSF protein, pleocytosis, negative antiaquaporin-4, antimyelin oligodendrocyte glycoprotein antibody levels, retinal nerve fiber layer thinning, and bilateral nerve sheath enhancement (Figures 1–2). The patient received penicillin and oral prednisolone, which improved her vision. Infectious causes of optic neuritis are complex (Table).1,2 NGS is an emerging method with the potential to rapidly identify atypical optic neuritis.

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.

Understanding Parinaud's Syndrome.

Parinaud’s syndrome involves dysfunction of the structures of the dorsal midbrain. We investigated the pathophysiology related to the signs and symptoms to better understand the symptoms of Parinaud’s syndrome: diplopia, blurred vision, visual field defects, ptosis, squint, and ataxia, and Parinaud’s main signs of upward gaze paralysis, upper eyelid retraction, convergence retraction nystagmus (CRN), and pseudo-Argyll Robertson pupils. In upward gaze palsy, three structures are disrupted: the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), interstitial nucleus of Cajal (iNC), and the posterior commissure. In CRN, there is a continuous discharge of the medial rectus muscle because of the lack of inhibition of supranuclear fibers. In Collier’s sign, the posterior commissure and the iNC are mainly involved. In the vicinity of the iNC, there are two essential groups of cells, the M-group cells and central caudal nuclear (CCN) group cells, which are important for vertical gaze, and eyelid control. Overstimulation of the M group of cells and increased firing rate of the CCN group causing eyelid retraction. External compression of the posterior commissure, and pretectal area causes pseudo-Argyll Robertson pupils. Pseudo-Argyll Robertson pupils constrict to accommodation and have a slight response to light (miosis) as opposed to Argyll Robertson pupils were there is no response to a light stimulus. In Parinaud’s syndrome patients conserve a slight response to light because an additional pathway to a pupillary light response that involves attention to a conscious bright/dark stimulus. Diplopia is mainly due to involvement of the trochlear nerve (IVth cranial nerve. Blurry vision is related to accommodation problems, while the visual field defects are a consequence of chronic papilledema that causes optic neuropathy. Ptosis in Parinaud’s syndrome is caused by damage to the oculomotor nerve, mainly the levator palpebrae portion. We did not find a reasonable explanation for squint. Finally, ataxia is caused by compression of the superior cerebellar peduncle.

The Third Eye Sees Double: Cohort Study of Clinical Presentation, Histology, Surgical Approaches, and Ophthalmic Outcomes in Pineal Region Germ Cell Tumors

Intracranial germ cell tumors (GCTs) predominantly occur in the adolescent and young adult population and are most frequently located at the pineal gland. Tumor masses in the pineal region may cause ophthalmic symptoms due to compression to the midbrain, frequently presenting with Parinaud syndrome and hydrocephalus due to aqueductal compression. We conducted a single-institution cohort study of primary, pineal region GCTs to characterize the clinical presentation, as well as associated ophthalmic and hydrocephalus outcomes. Fifty-six primary pineal GCTs were identified. Among the 40 isolated pineal region GCTs, 15 were germinomas while 25 were nongerminomatous GCTs. Among 43 cases of hydrocephalus, endoscopic third ventriculostomy was the primary treatment in 27 cases, which was successful in 23 but failed and required additional treatment for the rest. Pineal tumor mass was significantly larger in cases with hydrocephalus compared with those without, and the 20-mm diameter of the tumor was the crucial point for obstructive hydrocephalus. Ophthalmic symptoms were commonly observed at presentation, which included diplopia (74.3%), upward-gaze palsy (69.7%), and Argyll Robertson pupil (40%). These symptoms tended to remain, and the existence of these symptoms at presentation predicted the remaining symptoms in the follow-up. Intracranial GCTs presenting with ophthalmic abnormalities appear to be at increased risk of residual posttreatment symptoms, while second-look surgery presents a significant risk factor for the development of new deficits. Hydrocephalus often accompanies pineal region GCTs, and in most cases both cerebrospinal fluid diversion and tissue diagnosis can be successfully achieved via endoscopic third ventriculostomy.

Neurosyphilis With Psychosis as the Primary Presentation

Patients with neurosyphilis, which is now a rare disease because of the availability of antibiotics, can initially present with psychiatric symptoms instead of the more well-known physical findings, such as general paresis, tabes dorsalis, and Argyll Robertson pupils. A subset of patients with primarily psychiatric symptoms beginning later in life tend to be incorrectly diagnosed as having late-onset schizophrenia. This case report describes a 67-year-old female with psychiatric symptoms starting 8 years prior to presentation who was misdiagnosed with late-onset schizophrenia. Because her symptoms first appeared at the later age of 59, additional testing was performed to rule out a medical etiology. The patient was found to be positive for syphilis infection in the serum and cerebrospinal fluid. She displayed no other notable symptoms of syphilis aside from bizarre behaviors and paranoid delusions. This case demonstrates the importance of considering organic infectious diseases, such as syphilis, when psychosis initially presents at an older age.

Neurosyphilis, A True Chameleon of Neurology.

Background:Neurosyphilis (NS) is a rarely encountered scenario today. Manifestations are heterogeneous, and their characteristics have changed in the antibiotic era. A differential diagnosis of NS is not commonly thought of even with relevant clinical-radiological features, as it mimics many common neurological syndromes.Objectives:To study the manifestations of NS in the present era and the process of diagnosis.Method:The data of ten patients with NS was collected and analyzed. Their background data, clinical features, investigations, the process of reaching the diagnosis, management and outcomes were recorded.Observations and Results:The manifestations of NS in our cohort included six patients with cognitive decline/encephalopathy and one each with meningitis with cranial nerve palsies, cerebellar ataxia, myelitis and asymptomatic NS. The presence of Argyll Robertson pupil helped to clinch diagnosis in one patient. Treponemal tests were ordered in two patients only after alternative etiologies were looked at, to begin with, whereas in six patients treponemal test was requested as a part of standard workup for dementia/ataxia.Conclusions:NS dementia and behavior changes are mistaken for degenerative, vascular, nutritional causes, autoimmune encephalitis or prion disease. Meningitis has similarities with infective (tubercular), granulomatous (sarcoidosis, Wegener's), collagen vascular disease and neoplastic meningitis, and myelitis simulates demyelination or nutritional myelopathy (B12 deficiency). Rarely, NS can also present with cerebellar ataxia. Contemplate NS as one of the rare causes for such syndromes, and its early treatment produces good outcomes.

An unusual presentation of neurosyphilis with complicated pulmonary involvement in a patient without HIV infection

Background: Neurosyphilis could develop at any time in the course of syphilis; with an annual incidence of 0.7 per 100,000 men. Homosexual and HIV were risk factors. Here we report an unusual case of neurosyphilis in non-HIV patient with complicated pulmonary involvement. Case description: A fifty-six-year-old promiscuity, heterosexual man, active smoker presented with a three-month history of pruritic maculopapular rashes on his body associated with low-grade fever, and a two-week history of productive cough with dyspnea. On physical examination, he was tachypnea, with crackles on the base of the right lung. There was plaque hyperpigmentation on his malar area and multiple maculopapular, erythematous lesions on his trunk, extremities including palms of the hands, and scrotal area. No ulcer was found on his penis. Laboratory results revealed leukocytosis (19.9 × 103/μl), non-reactive HIV test, with high titer of serum VDRL (1/8) and TPHA (1/1280). Chest X-ray showed infiltrate on right perihilar area. Patient was diagnosed as pneumonia with secondary syphilis. The patient was treated with a single dose of benzathine penicillin G 2.4 million units intramuscular and azithromycin 500 mg tablet OD. During observation, he had altered mental status, generalized tonic seizure, high-grade fever with respiratory distress. He had Argyll Robertson pupil, left central facial and hypoglossal nerve paralysis, and positive meningeal signs, with normal brain CT scan result, non-reactive CSF-VDRL and TPHA, with high leucocyte (17 cells/μl) and protein (54 mg/dl). He was diagnosed neurosyphilis with hospital-acquired pneumonia and treated with ceftriaxone and vancomycin, 2 g OD and 750 mg OD intravenous, respectively. The patient showed no significant improvement and unfortunately, he progressed to death caused by multiple organ dysfunctions due to septic shock. Discussion: There is no single, highly sensitive and specific diagnostic test exists for neurosyphilis. The diagnosis of neurosyphilis is based on clinical findings and the results of serologic tests and CSF examination. The CSF-VDRL has sensitivity 30–70%, non-reactive test does not exclude neurosyphilis. Neurosyphilis in a patient without HIV infection could be diagnosed by a high WBC or protein in CSF with symptoms or signs of neurosyphilis even with non-reactive CSF-VDRL. Conclusion: Neurosyphilis could be considered even with a non-reactive CSF-VDRL result in non-HIV patient.

Location of the Ciliary Ganglion within the Orbit

The ciliary ganglion (CG) is a parasympathetic ganglion located in the orbit that controls pupil contraction, accommodation, ocular blood flow, intraocular pressure, and aqueous humor production. Micro and macro‐surgical lesions to the CG can affect nearby structures and lead to Adie’s Tonic Pupil or Argyll Robertson Pupil. This study was performed to better understand the CG location within the orbit. Few studies have analyzed the distance from the CG to neighboring structures with evident variation in the mean distance between the posterior globe (PG) and the CG, which can prove clinically significant in orbital floor surgical procedures. Besides direct clinical impact, this research would be beneficial in medical education by enabling a more accurate depiction of the CG in anatomical illustrations. Lastly, this is a novel study in that it measures the distance in relation to a relatively immobile structure, rather than to a more dynamic and variable neural or vascular structure.MethodsNine cadaver heads were bisected for a total of 18 samples, and two additional bisected half heads were used. The calvaria, brain, cranial fossa dura matter, frontal bone, and lesser wing of sphenoid bone were removed. Once orbital contents were visualized, dissection began by identifying the anterior and posterior ethmoidal nerves that run superior to the upper border of the medial rectus muscle. Blunt dissection was used to trace them back to the nasociliary nerve, an ophthalmic nerve division. The nasociliary nerve sends a sensory root to the CG. The oculomotor nerve (CN III) passes through the common tendinous ring, which was dissected open to allow better visualization of CN III inferior and superior divisions. The inferior division of CN III, which carries parasympathetic contribution to the CG, was dissected. The CG was confirmed by tracing the sensory nasociliary branch and the parasympathetic root from the inferior division of CN III to CG. Once identified, the CG was pinned in the center, in its natural position. The distance from the PG at the optic nerve juncture and the pinned CG was measured three separate times, removing and placing the pin in the center for each measurement. The three measurements average was used. The second measurement was from the posterior clinoid process (PCP) to the pinned ganglion, measured three separate times, and the average was used for each ganglion.ResultsThe average distance range between PG and CG was 8.95 – 24.63 mm, with the average of the 20 mean measurements being 17.853 mm. The average distance range between CG and PCP was 28.23 – 39.58 mm, with the average of the 20 mean measurements being 35.135 mm.ConclusionThe distance from the PG to the CG center was 17.85 mm, and from CG center to PCP was 35.135 mm. This varies from other studies that have reported the distance between the PG and CG to be 12 mm, 2–3 mm, and 15–20 mm. The CG is 2.9 mm lateral to the optic nerve and could be damaged during lateral orbiotomy procedures. In terms of anatomical education, illustrations in Netter and Gray’s differ in the location of the CG. These results support Gray’s proposition that the CG is further posterior relative to the posterior globe rather than being closer to the globe as shown in Netter’s atlas. Ours is a novel study to clarify the position of the CG within the orbit.

Neurosyphilis-associated movement disorder: A literature review

Syphilis is a well-known “great simulator/mimicker” of other diseases. Over the last decades, the clinical features of neurosyphilis have changed with an increasing percentage of atypical manifestations. In this context, movement disorders caused by neurosyphilis are rare and challenging to diagnose. This literature review aimed to evaluate the clinical epidemiological profile, pathological mechanisms, and historical features of neurosyphilis-associated movement disorders. Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 84 reports containing 168 cases who developed a movement disorder related to neurosyphilis were reported. The mean and the median reported ages were 40.50 (standard deviation [SD], 20.30) and 43 years (2.5–72.5 years). The predominant sex was male (79.16%). Argyll Robertson pupils were found in 54.90% of the individuals. The movement disorders reported were tremor, chorea, parkinsonism, ataxia, myoclonus, dystonia, athetosis, and ballism. In the literature, we have a large number of reports about movement disorder associated with neurosyphilis. But, in the majority of them, the individuals had the syphilitic diagnosis based on unspecific methods, electrodiagnostic studies were not performed, or penicillin therapy was unavailable. Also, we believe that any patient presenting with a movement disorder should have a thorough neurological examination of pupillary reflex, and if any abnormality is present, syphilitic laboratorial tests should be done.

All eyes on him: Argyll Robertson pupil in late syphilis

All eyes on him: Argyll Robertson pupil in late syphilis

A Novel Asp121Asn Mutation of Myelin Protein Zero Is Associated with Late-Onset Axonal Charcot-Marie-Tooth Disease, Hearing Loss and Pupil Abnormalities.

Myelin protein zero (MPZ) is a major component of compact myelin in peripheral nerves. Mutations in MPZ have been associated with different Charcot–Marie–Tooth disease (CMT) phenotypes (CMT1B, CMT2I/J, CMTDI), Dejerine–Sottas syndrome, and congenital hypomyelination neuropathy. Here, we report phenotypic variability in a four-generation Chinese family with the MPZ mutation Asp121Asn. Genetic testing was performed on nine family members and 200 controls. Clinical, electrophysiological and skeletal muscle MRI assessments were available for review in six family members. A novel heterozygous missense mutation, Asp121Asn, was observed in five affected members of the family. Unaffected relatives and 200 normal controls were without the mutation. Four of the affected members of the family displayed late-onset, predominantly axonal sensory and motor neuropathy, pupil abnormalities, and progressive sensorineural hearing loss. One young affected member presented with Argyll–Robertson pupils and diminished deep tendon reflexes in the lower limbs. The MPZ mutation Asp121Asn may be associated with late-onset axonal neuropathy, early onset hearing loss and pupil abnormalities. Our report expands the number and phenotypic spectrum of MPZ mutations.

Douglas Moray Cooper Lamb Argyll Robertson (1837-1909).

Douglas Moray Cooper Lamb Argyll Robertson (1837-1909).

Neurosyphilis Presenting Unilateral Oculomotor Nerve Palsy and Bilateral Pupil Involvement

Of the symptomatic disorders associated with neurosyphilis, the earliest manifestation is syphilitic meningitis. Approximately 5% of patients with secondary syphilis develop associated meningitis. Headaches, meningismus, cranial nerve palsies (chiefly, in descending order of frequency, VII, VIII, VI, and II. Here, we report a case of neurosyphilis presenting as unilateral oculomotor nerve palsy with bilateral pupil involvement (Argyll-Robertson pupil). A 43-year-old male presented with diplopia in both eyes at a neurology clinic 2 weeks before. He had right paralytic blepharoptosis, and both pupils were fixed and both pupils were not observed direct and indirect reflex and anisocoric. We observed Argyll Robertson pupil. He had 35 prisms of right exotropia, 2 prisms of right hypertropia at near and distance in the state of primary deviation and 60-prism right exotropia and 4- prism hypertropia in the state of secondary deviation. He had extraocular movement disorder in all gazes except abduction. We considered oculomotor nerve palsy associated with neurosyphilis based on the Argyll Robertson pupil. His orbit MRI suggested right oculomotor neuritis due to the presence of diffuse thickening of the right oculomotor nerve with enhancement. Finally, he was diagnosed with syphilis as a result of CSF protein 96.0, VDRL 7.5, and FTA-ABS (+) and was administered penicillin (4,000,000 units) and oral steroid (50 mg). One week after, his intraocular pressure was in the normal range. Extraocular movement examination findings were favorable as a result of 20-prism right exotropia at near and distance in the state of primary deviation and 35-prism right exotropia in the state of secondary deviation. He had extraocular movement disorder only in upper gaze. A diagnosis of neurosyphilis should be considered in patients with serologic evidence of syphilis and one or more of the following cerebrospinal fluid abnormalities; mononuclear pleocytosis, elevated protein, increased immunoglobulin G, or the presence of oligoclonal bands.

Eponyms in syphilis.

Eponym has originated from the Greek word "eponymos" meaning "giving name". It is a tribute to the pioneers in the field who have significantly contributed towards present understanding of the subject. Syphilis has amazed and plagued mankind since eternity. This disease is a great masquerade and can humble best of physicians with its varied presentations. Keen and immaculate observations of these workers have eased our understanding of many signs and phenomenon associated with this disease. This has led to evolution of number of eponyms, perhaps no other disease has as many eponyms associated with it, as does syphilis. Eponyms such as Kassowitz's law, Clutton's joints, Higoumenaki sign, Argyll-Robertson pupil etc. help in providing easy milieu for remembering. Besides paying tributes to stalwarts in the field, who dedicated their lives for this cause, they also facilitated our current understanding of the great masquerade.

WITHDRAWN: A third nerve palsy with an Argyll Robertson pupil

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Foster Kennedy Syndrome

Foster Kennedy Syndrome

MRI findings and early diagnosis of general paresis of the insane

The objective of this study was to improve the knowledge of the clinical and MRI presentation of general paresis of the insane (GPI) and achieve its early diagnosis. Fifteen patients with GPI were gathered. Their clinical data and brain MRI information were analyzed. The age range was 33–62 years (mean: 48·8 years). The disease lasted 34 days–28 months (mean: 10·87 months). Treponema pallidum hemagglutination assays (TPHAs) on the cerebrospinal fluid (CSF) and sera were positive. All patients were human immunodeficiency virus (HIV) negative and primarily showed progressive cognitive impairment, mostly accompanied with emotional disturbance and psychosis. The accompanying symptoms included epilepsy (n = 7), ataxia (n = 5), cerebral vascular disease (n = 3), and limbs tremor (n = 2). Typical Argyll Robertson's pupil was observed in two cases. A CSF examination showed elevated white blood cell (WBC) and protein level. Purely cerebral atrophy was found in three cases. Abnormal high signals were found in nine cases in different brain area, mainly in bilateral temporal, insular, and frontal lobes and hippocampus in T2-weighted and fluid-attenuated inversion recovery (FLAIR), which was accompanied by cerebral and/or hippocampus atrophy. Purely atrophy of bilateral or unilateral hippocampus was found in two cases. Cerebral infarction lesions were found in three cases. Contrary to the previous reports, the hippocampal atrophy and bilateral abnormal signals of hippocampus and temporal lobe in brain MRI were more common in cases with GPI. Abnormal signals were probably related to proliferation of glial cells rather than cytotoxic edema. The pathogenesis of the abnormal signals needs to be further explored. General paresis of the insane has a wide variety of central nervous system manifestations, either clinically or neuroradiologically. Identification of these presentations could be important for early diagnosis.

Neurosyphilis in a young patient presented as rapid cognitive decline: Case report

We present the case of a 38 year /INS;old man who was admitted for a rapid cognitive decline and headache. CT and MRI studies revealed a normal pressure hydrocephalus. He was assessed for surgery and a ventriculo-peritoneal shunt was realized. Neurologic examination revealed mild spastic tetraparesis, right Argyll-Robertson pupil, gait disturbance, severe cognitive decline with amnestic aphasia and asymmetric myoclonic jerks predominantly in the lower limbs. The CSF showed normal pressure, 12 lymphocytes/mm3, 0.55 g/L proteins, and positive TPHA test. Serum TPHA and VDRL were intense positive at small dilutions with negative HIV serology. EEG showed a theta rhythm with intermittent generalized triphasic discharges. Psychiatric and neuropsychological examinations showed a MMSE test of 12 with anterograde amnesia, nominal aphasia, and /INS;ideomotor apraxia. The final diagnosis was neurosyphilis with moderate–/INS;severe dementia and the patient received ceftriaxone 4 g /INS;intravenous daily. Mild improvement of the symptoms was observed, but the patient must be reassessed periodically.

The great pox

How many physicians have seen a patient with tabes dorsalis or an Argyll Robertson pupil? In the 1960s, they turned up in the MRCP examinations but it was always a surprise to see a new patient with neurosyphilis in the clinic. I remember the last one in whom I, working as a registrar in that era, made the diagnosis. He had worked for decades in West Africa and his ataxia and high-stepping gait, which he had attributed to old age, was quite distinctive. Some time before I saw him, I met a man with general paralysis of the insane (GPI). Indeed, I met several. My father used to take me, a schoolboy, to see his patients on the tropical diseases ward on Saturday mornings, presumably to give my mother respite. It was the early 1950s and penicillin was not widely available in the new NHS. This man was friendly and very talkative; he believed that he was a wireless and invited me to tune him in by turning knobs that he said were on his arm. He then produced an imitation of the home, light or third programmes. The story has a happy ending. He responded well and went home to his sweetie …