The 45th meeting of the Upper Midwest Neuro-Ophthalmology Group (UMNOG), hosted by University of Illinois at Chicago, took place on 21 July 2023, in Chicago, Illinois. John Chen, MD, PhD, Mayo Clinic, Rochester, Minnesota, and Collin McClelland, MD, University of Minnesota, Minnesota, co-organised the meeting. Fifty-one people attended the meeting in-person with 17 podium presentations.
To begin the meeting, Michael S Lee, MD, University of Minnesota, presented a case of a 67-year-old female who presented with binocular diplopia and right hemicranial pain. She was found to have a partial 3rd nerve palsy as well as reduced sensation in the right V1 and V2 distribution. Magnetic resonance imaging (MRI) of her head showed an enhancing lesion along the right orbital apex and right anterior cavernous sinus. She was started on oral prednisone but was lost to follow up. Six months later, she returned with a new right 6th nerve palsy and right V3 numbness despite being continued on high dose oral prednisone. A further MRI showed interval progression of the enhancing lesion. A cavernous sinus biopsy was performed, and 16S rDNA analysis, which is a culture-free method to identify bacteria, demonstrated Cutibacterium acnes. Her symptoms resolved with oral penicillin, suggesting C. acnes as the cause of her cavernous sinus syndrome. This case illustrated a primary intracranial infection with C. acnes in the absence of a prior neurosurgical intervention and highlighted the use of 16S rDNA analysis for identifying atypical infections.
Nanthaya Tisavipat, MD, Mayo Clinic, presented a multicentre, case–control study comparing characteristics of unilateral optic neuritis from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in older adults to age- and sex-matched non-arteritic ischaemic optic neuropathy (NAION) patients. MOGAD patients over the age of 45 presenting with their first attack of unilateral optic neuritis were included. Sixty-five patients were identified in each group. The median age at onset was 56 years, and 71% were female. Rates of diabetes mellitus, hypertension, and cardiovascular disease were similar between MOGAD and NAION patients, but dyslipidaemia, obstructive sleep apnoea, smoking, and crowded optic discs were more common among NAION patients. Vision worsening beyond 48 hours (46% versus 25%), preceding headache (47.7% versus 21.5%), eye pain (80% versus 21.5%), and increased pain on eye movement (80.5% versus 14.3%) were significantly more common in MOGAD patients. The degree of optic disc oedema and retinal nerve fibre layer (RNFL) thickness in MOGAD patients was less pronounced than in NAION patients (median 114 versus 208 μm; increase 25 versus 102 μm). Around one-third of each group had the other diagnosis (NAION vs optic neuritis) noted as a differential in the chart. Although MOGAD patients had more severe visual acuity loss at nadir (20/200 versus 20/40), recovery was better (20/25 versus 20/40). These findings suggest that in older adults, the presence of vascular comorbidities does not exclude MOGAD. Typical clinical features of MOGAD are important clues for further investigation, but there is some overlap between MOGAD and NAION cases.
Letitia Pirau, MD, University of Michigan, presented a case of a 74-year-old male who reported confusion, nausea, vomiting, and complete bilateral loss of vision at the conclusion of a right internal carotid stenting procedure. During the procedure, contrast dye was injected into the carotid and vertebral arteries. His visual acuity was no light perception in each eye, with normal pupillary reactions and no ocular structural abnormalities. Computed tomography (CT) angiography (CTA) of the head and neck was unremarkable. An electroencephalogram (EEG) showed non-convulsive status epilepticus (NCSE) in the occipital lobe without ictal behaviour. He was treated with intravenous (IV) fosphenytoin. An MRI disclosed subtle occipital T2 fluid attenuated inversion recovery (FLAIR) hyperintensities without restricted diffusion or contrast enhancement. The patient was diagnosed with contrast-induced encephalopathy (CIE), which can occur from vascular endothelial damage with contrast dye toxicity. Although this case clinically mimicked a stroke, the lack of diffusion-weighted high signal and normal apparent diffusion coefficient on MRI excluded acute cerebral infarction, contraindicating emergent thrombolysis. The patient’s visual acuity returned to baseline 48 hours after onset. This case highlighted that NCSE should be in the differential diagnosis for vision loss presenting with CIE and that an EEG should be considered to evaluate for NCSE.
Devon A. Cohen, MD, Cole Eye Institute-Cleveland Clinic Foundation, presented the narrative review of six patients who underwent venous sinus stenting (VSS) for fulminant idiopathic intracranial hypertension (IIH) that had been published in the literature. Dr Cohen then discussed three patients who underwent VSS for fulminant IIH at the Cole Eye Institute in 2023. All were women with mean BMI of 43.8 kg/m2, a mean onset to vision loss of 10 days, and opening pressures ranging from 33 to 48 cm of cerebrospinal fluid (CSF). All had bilateral transverse sinus stenosis on magnetic resonance venography. After unilateral VSS, two patients had improvement in symptoms and visual fields, and one patient was lost to follow-up. Although the sample size was limited, these cases suggested that VSS is at least noninferior to VP shunting. However, the audience discussed the need for antiplatelet therapy for 3 months after VSS, which could make it difficult to do another emergent procedure if VSS was not successful in the setting of fulminant IIH. The authors reinforced the need for future study to compare the treatment modalities in fulminant IIH.
Veeral Shah, MD, PhD., University of Cincinnati Children’s, discussed the results of a retrospective chart review examining the incidence of nystagmus, clinical characteristics, and visual outcomes in infants with intrauterine drug exposure (IUDE). Out of 2404 patients with IUDE, 118 (4.9%) were diagnosed with nystagmus. The average gestational age was 36.5 weeks, and 31.4% of these patients were born prematurely (<37 weeks). The most common drug of abuse was methadone (51.7%). Out of 75 patients who had neuroimaging, 42 (56%) patients had abnormal radiological findings. Ophthalmological sequelae of IUDE included strabismus (44%), refractive error (23.7%), optic nerve hypoplasia (9.3%), and abnormal retinal findings (9.3%). There was a high prevalence of exposure to opioids (71.2%) or therapeutic opioid alternatives (89.3%) in infants with IUDE and nystagmus. The study also highlighted the importance of neuroimaging in children with IUDE and nystagmus.
John J Chen, MD, PhD, Mayo Clinic, proposed a multicentre prospective randomised clinical trial to confirm the efficacy of early plasma exchange (PLEX) in optic neuritis. From a prior large retrospective study, poor visual outcomes in optic neuritis patients treated with PLEX were associated with increased age, worse visual acuity on presentation, and most importantly, time to PLEX, which was the only modifiable factor. In this proposed trial, patients would be divided into two groups: one group receiving IV methylprednisolone (IVMP) only and another group receiving PLEX in addition to IVMP. If there was no recovery on IVMP only, the patients could cross over to the PLEX group after 14 days. The visual outcomes and time to recovery would be documented. Although the study would not be double-blinded and the costs and potentially adverse effects of PLEX should be considered, the authors demonstrated the need for a clinical trial to study the efficacy of early PLEX. There was a lively discussion about the pros and cons of the proposed trial.
Mangay Thandampallayam, MD, University of Kentucky, presented a case of a 61-year-old female who was evaluated for right-sided ptosis, right orbital pain, and diplopia. She was found to have a pupil involving 3rd nerve palsy and bilateral 6th nerve palsies. Initial MRI of her brain and orbits was read as normal. Her erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level were mildly elevated, and corticosteroids were started with no improvement. A repeat MRI showed an enhancing lesion in the right cavernous sinus with concern for perineural spread and enhancement of the right oculomotor nerve. CTA of the head and neck was unremarkable. A lumbar puncture revealed a normal opening pressure and no evidence for infection, but CSF flow cytometry suggested B-cell lymphoma. MRI of her cervical, thoracic, and lumbar spine showed increased cervical lymphadenopathy. Due to acute liver injury, she underwent a liver biopsy, which showed lymphoma involvement. Positron emission tomography (PET) showed extensive hypermetabolic lymphadenopathy. She was ultimately diagnosed with a diffuse large B-cell lymphoma and was treated with rituximab, prednisone, and intrathecal methotrexate, but she died within 1 month of diagnosis. This case represented a rare infiltrative cavernous sinus syndrome with an aggressive diffuse large B-cell lymphoma.
Evan Jameyfield, MD, Washington University in St. Louis, presented a case series of four patients with fulminant papilloedema and comorbid nutritional deficiencies (folate, vitamin B12, and thiamine). Despite aggressive treatment and improvement in their papilloedema, or even with no recurrent papilloedema, these patients worsened. After nutritional deficiencies were identified and corrected with supplementation, the patients’ visual function stabilised. These cases emphasised the observation that patients with obesity or other risk factors for IIH may also be at increased risk for nutritional deficiencies. For those who initially present with papilloedema and visual loss, the authors recommended screening for nutritional deficiencies and initiating appropriate supplementation, which may improve visual outcome. The audience also discussed the importance for screening for concomitant anaemia, which has also been shown to be linked with IIH.
Meari Taguchi, MD, University of Michigan, presented a case of a 43-year-old man who came in with bilateral dilated and non-reactive pupils with impaired near vision. He had a fairly comitant esophoria and a subtle difficulty with tandem gait. Both pupils constricted with 1% pilocarpine. A few days later he presented with new double vision and worsening headache. Alternate cover testing revealed a small right hyperphoria and an incomitant esotropia. There was hyporeflexia and difficulties with tandem gait. MRI and a lumbar puncture showed no abnormalities. GQ1b returned positive with a titre of 1:800, confirming the diagnosis of Miller Fisher syndrome. He was treated with intravenous immunoglobulin, which improved his symptoms. This case described a rare initial manifestation of Miller Fisher syndrome presenting with internal ophthalmoplegia as the predominant clinical feature.
Jeremy Shapiro, BA, University of Michigan, presented a single-institution retrospective study of patients who were diagnosed with third nerve palsies secondary to intracranial aneurysms and had undergone interventions for the aneurysms. Recovery was categorised as ‘complete’, ‘non-disabling incomplete’, and ‘disabling incomplete’, based on medical record documentation and patient self-report telephone interviews. The questions were mostly centred on residual diplopia in primary gaze, a narrow zone of single binocular vision, and visual-obscuring ptosis. Among 33 patients, 13 (39%) had complete recovery, and 11 (33%) had ‘disabling incomplete’ recovery from diplopia or ptosis. Of the six patients who underwent ophthalmological interventions, disability was relieved in only two patients. Aneurysmal clipping was associated with a favourable outcome compared with other treatment modalities. With a novel method of assessing disability, this study showed that more than one-quarter of patients undergoing procedures for brain aneurysms had lingering disability from diplopia or ptosis despite later ophthalmological interventions.
Padmaja Sudhakar, MD, University of Kentucky, presented a case of 52-year-old man referred by his optometrist for bilateral optic disc elevation. He reported pulsatile tinnitus but no headaches or vision loss. He had a history of childhood-onset muscle weakness with bone abnormalities leading to a diagnosis of Camurati – Engelmann disease, an autosomal dominant disease caused by a TGFB1 gene mutation. He had had bilateral sensorineural hearing loss for 17 years and bilateral proptosis for 10 years. MRI revealed optic canal stenosis. Optical coherence tomography (OCT) showed thin RNFLs bilaterally. The patient was felt to have a chronic and stable optic neuropathy from optic canal stenosis. Neuro-ophthalmological manifestations of Camurati-Engelmann disease are rare but can result from cranial vault bone overgrowth. Vision loss may result from optic nerve compression at the optic canal, glaucoma, globe distortion, or increased intracranial pressure. Proptosis, hearing loss, facial palsies, and meningo-encephalomyelocoeles can occur. Severe cases may require surgery, such as skull base repair or cranial vault expansion.
Minjun Hur, MD, Mayo Clinic, presented a case series of two patients with bilateral papillitis without optic nerve enhancement on MRI. These patients were found to have inflammatory CSFs with increased leukocytes and total protein in addition to CSF IgLON5 positivity. Neither of these patients had sleep or gait abnormalities. Although various neurological manifestations have been described with anti-IgLON5 disease, such as sleep disorders, gait instability, dysphagia, cognitive decline, and a progressive supranuclear palsy-like syndrome, isolated optic neuropathy has not previously been reported. The authors suggested that these cases of isolated bilateral papillitis without significant neurological manifestations could be a potential phenotype of IgLON5 and that future work is required to confirm this phenotype of IgLON5 optic neuropathy.
John Mitchell, MD, Marshfield Clinic, presented a 63-year-old female with horizontal and vertical diplopia, nausea, and balance problems for 12 days. There was also a foreign body sensation in the left eye. Examination showed left ptosis, a right hypertropia worse on left head tilt, left miosis with anisocoria greater in the dark, and decreased temperature sensation in the right arm and leg. His left eye also had conjunctival injection and filamentary keratitis. Apraclonidine drop testing confirmed the diagnosis of a left Horner’s syndrome. MRI showed a brainstem stroke and the patient was diagnosed with a left lateral medullary syndrome (Wallenberg’s syndrome). Although the pattern of the hypertropia mimicked a 4th nerve palsy, the diplopia was felt to be caused by a skew deviation given the known involvement of the medulla. The cornea findings were consistent with neurotrophic keratitis from V1 dysfunction-related neurotrophic cornea. CTA or magnetic resonance angiography (MRA) of the neck was recommended to identify the aetiology of the stroke.
Sangeeta Khanna, MD, University of Michigan, discussed a case of 45-year-old man with acute painless right-eye vision loss. He had a history of hypertension and had undergone urgent surgery 2 weeks previously for acute type A aortic dissection. His visual acuity was hand motion in the right eye and 20/60 in the left eye with a left eye temporal visual field defect. Fundus examination showed scattered retinal haemorrhages from hypertensive retinopathy but normal optic discs. Orbital MRI demonstrated gadolinium enhancement within the optic chiasm and the right prechiasmatic optic nerve, and multiple punctate areas of restricted diffusion in the cerebral white matter. The optic chiasm and prechiasmal area have a complex vascular supply from both anterior and posterior circulations, so infarction rarely occurs. However, Dr Khanna discussed that the medical literature contains three previously reported cases of chiasmal infarction, including one after a cardiopulmonary bypass procedure. The proposed mechanism in this case was emboli after the dissection repair. This case demonstrated a rare cause of chiasmal enhancement from infarction causing a junctional scotoma.
Francisco R. Sanchez Moreno, MD, Neuro-ophthalmology of Texas, PLLC, shared a case of 34-year-old male with sudden right retrobulbar pain and right temporal headache, followed by sudden onset blurriness in the right eye peripheral vision 10 days later. Over the next 4 days, his vision worsened to 20/100 in the right eye, and fundus examination showed right optic disc oedema. He had leukocytosis and an elevated CRP level with a normal ESR. His CSF had a borderline protein level, but red blood cells were markedly elevated. He was negative for serum anti-human immunodeficiency virus, serum and CSF syphilis testing, and serum Bartonella henselae IgM and IgG. Although the brain MRI/MRA was reportedly normal, the patient was treated with 3 days of IVMP, which improved his vision to 20/40. Repeated examination before discharge revealed superior right optic disc oedema with juxtapapillary retinochoroiditis. There were no cells or macular exudates seen, but OCT showed signs of vitritis. His serum toxoplasma IgM returned positive and later converted to IgG, suggesting an uncommon presentation of papillitis from toxoplasmosis.
The last podium presentation was delivered by Aseem Sharma, MBBS, University of Michigan, on the reliability of orbital MRI for the diagnosis of bilateral optic neuritis. In this study, six masked readers, including trainees and neuroradiologists, were asked to review 80 fat saturated orbital FLAIR and gadolinium-enhanced MRIs (20 bilateral optic neuritis; 30 unilateral optic neuritis; 30 normal controls). Each optic nerve was rated for T2 prolongation and gadolinium enhancement on a scale of 1 (definitely normal) to 5 (definitely abnormal). Detection rates of T2 hyperintensity (82.7% versus 45.5%) and enhancement (78.9% versus 56.7%) were significantly higher in unilateral compared with bilateral optic neuritis. The sensitivity for bilateral optic neuritis detection was 29.5%, based on T2 hyperintensity and 47.5%, based on enhancement. Interobserver agreement for the detection of bilateral optic neuritis was also lower than unilateral optic neuritis among residents and fellows but not among neuroradiologists. These data demonstrated that interpretation of optic nerve signal abnormality is more difficult when both sides are involved.
Flea circus cases
The Flea Circus Cases had been brought back this year by request from attendees. Five cases were presented at the meeting.
Adeela M. Alizai, MD, Indiana Eye Institute, presented a 9-year-old boy with intermittent ptosis in the left eye. Serum anti-acetylcholine receptor antibodies were negative. MRI showed multiple intracranial masses, including bilateral vestibular schwannomas. He was diagnosed with neurofibromatosis type 2. Repeated MRIs showed tumour enlargement and multiple new central nervous system tumours over the following 2 years. The patient developed high-frequency sensorineural hearing loss, and choroidal and iris naevi. The main question was about management strategy. Potential enrolment in clinical trials for molecular targeted pharmacotherapy was suggested. The role of serial examination and imaging and the threshold for debulking surgery were discussed.
Nikita Saladi, MD, Medical College of Wisconsin, presented a 71-year-old woman with a history of multiple myeloma treated with a bone marrow transplant. She presented with acute vision loss in the right eye without pain on eye movement. Examination showed a superior altitudinal visual field defect and optic disc oedema in the right eye and a crowded optic disc in the left eye. The ESR and CRP level were elevated. Orbital MRI showed marked bilateral optic nerve sheath enhancement, which was more prominent towards the globes. The CSF was unremarkable. She was treated with IVMP and escalated to PLEX when her visual acuity dropped to light perception. Her right-eye vision recovered to 1/200 at 2 months. Giant cell arteritis (GCA), multiple myeloma infiltration, atypical NAION, medication adverse effects, and paraneoplastic or infectious process were on the differential diagnosis. Bilateral perineural enhancement has been reported in GCA and therefore the audience felt this may be the most likely diagnosis. Diagnostic investigations were discussed, and temporal artery biopsy was strongly suggested. Optic nerve sheath biopsy could also be considered if the temporal artery biopsies were negative and the optic nerve sheath enhancement persisted.
Lina Nagia, DO, Michigan State University Health Care, shared a 76-year-old woman who had binocular oblique diplopia and right-eye ptosis. Examination revealed abduction and adduction deficits, proptosis, and tortuous scleral vessel in the right eye. In MRI, there was a homogeneously enhancing soft tissue mass in the right orbit, encasing the globe. Right medial orbitotomy with mass biopsy was performed. A non-encapsulated, white firm mass was found, and pathology demonstrated inflammatory cells, fibrosis, and increased IgG4. She was diagnosed with IgG4-related disease, and the mass completely resolved with high-dose corticosteroids and rituximab.
Neena R. Cherayil, MD, Northwestern University, presented a 22-year-old male with subacute bilateral vision loss that started with central scotomas. His vision deteriorated during the first 3 months and became light perception in both eyes by 9 months after onset. Fundoscopic examination showed pale optic discs, and MRI showed dilated perioptic spaces, mild flattening of the globes, and markedly narrow optic canals. The internal acoustic canals were also narrow, but there appeared to be no bone abnormalities. There was gadolinium enhancement in the left optic nerve, which was only seen on one slice. His vision did not improve with IVMP. A mitochondrial panel for hereditary optic neuropathy was negative, so the questions posed were as follows: 1) should whole exome or whole genome sequencing be pursued?; and 2) would optic canal decompression improve his vision which had been stable for 6 months? The audience’s opinion steered towards obtaining further genetic testing before deciding on surgery.
Nayanika Challa, MD, University of Illinois College of Medicine, closed off the meeting with a 17-year-old girl with an enlarging blind spot in the left eye. She had had headaches, transient visual obscuration, and pulsatile tinnitus for 2–3 weeks. Examination revealed a visual acuity of 20/30 in the left eye with grade 3–4 optic disc oedema. MRI showed a homogeneously enhancing round mass involving the left optic nerve with no calcification on a CT scan. Her lumbar puncture opening pressure was 36 cmCSF, so she was treated with acetazolamide, which did not improve her vision. Given the unclear nature of the orbital mass, PET and gallium-68 (68Ga)-labelled dodecane tetraacetic acid-tyrosine-3-octreotate (DOTATATE) PET/CT were performed, which suggested an optic nerve glioma over an optic nerve sheath meningioma. Although she had stable visual acuity, the visual field defect progressed. Chemotherapy with carboplatin and vincristine and radiation therapy were recommended. The concern for neurodevelopmental delay from radiation was low since she was already a late adolescent. Optic nerve sheath fenestration was discouraged due to the distorted anatomy.