Bilateral Optic Neuritis Research Articles

A bilateral optic neuritis side effect of biological treatment with pembrolizumab in a patient with metastatic melanoma

Pembrolizumab is an anti-PD-1 humanized monoclonal antibody, standardized therapy for the treatment of metastatic melanoma, providing an overall survival benefit to patients; however, it may be associated with immune-related adverse effects (irAE). We describe the case of a patient with a history of metastatic melanoma undergoing treatment with pembrolizumab, who presented visual acuity deterioration due to inflammatory involvement of the optic nerves. There are few reported cases of an optic neuritis side effect of treatment with immune checkpoint inhibitors. The patient received high doses of steroids and plasmapheresis with improved light perception. This case highlights the need to recognize atypical processes, mediated by the immune system, associated with treatment with immune checkpoint inhibitors (ICI), including pembrolizumab.

Bilateral Optic Neuritis in a Child with Typhoid Fever – A Rare Case Report

Bilateral Optic Neuritis in a Child with Typhoid Fever – A Rare Case Report

Bilateral Optic Neuritis Associated with Central Nervous System Infection in an Adult

Bilateral Optic Neuritis Associated with Central Nervous System Infection in an Adult

Disease of the Year: COVID-19 and Its Neuro-ophthalmic Complications.

Disease of the Year: COVID-19 and Its Neuro-ophthalmic Complications.

Epidemiology of Pediatric NMOSD in Germany and Austria.

Background: Neuromyelitis optica spectrum disorders (NMOSD) are severe inflammatory demyelinating disorders of the central nervous system mainly characterized by recurrent episodes of uni- or bilateral optic neuritis (ON), transverse myelitis (TM) and brainstem syndromes (BS). The majority of adult patients has serum antibodies directed against the water channel protein aquaporin 4 (AQP4-abs). In pediatric patients, AQP4-abs are less, while antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) are more frequently detectable than in adults. Some children with NMOSD have neither AQP4- nor MOG-ab (double-seronegative).Objective: Evaluation of epidemiological data regarding incidence and prevalence of pediatric NMOSD in Germany and Austria.Methods: We recruited pediatric NMOSD patients between 1 March 2017 and 28 February 2019 with five different tools: (1) ESPED (Surveillance Unit for Rare Pediatric Disorders in Germany), (2) ESNEK (Surveillance for Rare Neurological Disorders during Childhood), (3) pediatric neurology working group within the Austrian Society of Pediatrics and Adolescent Medicine, (4) BIOMARKER Study and (5) NEMOS (Neuromyelitis optica Study Group). We requested data regarding clinical symptoms, antibody status, therapy regimen and response via a standardized questionnaire.Results: During the 2-year recruitment period, 46 (both incidental and prevalent) patients with a suspected diagnosis of NMOSD were brought to our attention. Twenty-two of these patients did not fulfill the inclusion criteria. Of the remaining 24 children, 22 had a median age at onset of 11 (range 3–17) years and 16/22 were female (72.7%) (no data in two patients). Sixteen of 24 patients were AQP4-ab positive (67%), 4/24 MOG-ab positive (16.7%), three children were double-seronegative and in one patient no antibody testing was done. We calculated an incidence rate of 0.022 per 100,000 person-years for Germany, while there was no incidental case in Austria during the recruitment period. The prevalence rate was 0.147 and 0.267 per 100,000 persons in Germany and Austria, respectively.Conclusion: Pediatric NMOSD, with and without associated antibodies, are very rare even considering the different limitations of our study. An unexpected finding was that a considerable proportion of patients was tested neither for AQP4- nor MOG-abs during diagnostic work-up, which should prompt to establish and disseminate appropriate guidelines.

High association of MOG-IgG antibodies in children with bilateral optic neuritis.

Bilateral optic neuritis (bilON) is a rare clinical presentation often thought to be associated with relapsing disorders such as neuromyelitis optica spectrum disorders (NMOSD) or multiple sclerosis (MS). To characterize the clinical, radiological phenotype and antibody status of children presenting with bilON. Retrospective multicenter study on children with bilON age <18 years with a first episode aquired demyelinating syndrome (ADS), cMRI, AQP4- and serum MOG-antibody status and follow-up data were collected. 30 patients (f:m=15:15, median age 8.0y) with bilON met the inclusion criteria. 22/30 (73%) were MOG-positive (median: 1:1280, range: 1:160-1:1520). No patient showed AQP4-abs. 4/30 patients (13%), all with high MOG-abs titers, had recurrent episodes. No patient developed MS. Improvement after IVMP was observed in most patients (26/30; 87%). Outcome was favorable with no sequelae in 22/30 patients. Serial MOG-abs titers tested in 15/22 patients decreased to a median of 1:160 (range: 0-1:640) over a period of 31 months (range: 2-141 months) in 14/15 (93%) patients. MR imaging showed a predominantly anterior affection of the visual system in seropositive patients with bilateral intraorbital lesions in 68% (15/22), compared to 25% in MOG-negative patients (2/8). Pediatric bilON is associated with high MOG-abs titers in combination with anterior involvement of the visual system. Despite severe loss of vision, the majority of patients shows distinct recovery after IVMP.

Isolated bilateral optic neuritis revealing a Lyme Disease : case report

Optic neuritis (ON) is an inflammation of the optic nerve and one of the most common manifestations of central nervous system involvement caused by various etiologies. Lyme optic neuritis is a rare ocular manifestation of Lyme Disease. We report a case of a 13-year-old male patient, previously healthy, with decreased central visual acuity on his both eyes . On examination, best-corrected visual acuity on both eyes was 0,3 LogMar. Anterior segment biomicroscopy showed no inflammatory signs and the intraocular pressure was normal. A fundus examination performed under mydriasis revealed a swollen optic disk on both eyes confirmed by fluorescein angiography. The cerebrospinal fluid examination and Lyme Disease blood findings were positive. The diagnosis of Lyme disease-related optic neuritis was made. Treated with Ceftriaxone and Doxicycline, there was a vision recovery. We can state that isolated bilateral optic neuritis is uncommon and exceptional especially in children during Lyme disease.

Use of ganglion cell layer analysis for diagnosing anti-glycoprotein neuromyelitis optica of oligodendrocyte myelin

The case concerns a 26-year-old patient with bilateral recurrent optic neuritis episodes in the context of suspected neuromyelitis optica. In the first outbreak, she had greatly impaired visual acuity of the left eye, as well as seeing ganglion cell layer damage in both eyes in the optic coherence tomography, with evidence of a possible extensive lesion in the optic chiasma. Likewise, MRI with contrast showed a great involvement of the left optic nerve that compromises the chiasma increasing the suspicion of a neuromyelitis origin. Althogh the anti-myelin oligodendrocyte glycoprotein (MOG) and anti-AQP4 (aquaporin-4) antibodies were negative at first, bilateral involvement of the ganglion cells suggested an extensive lesion that is more characteristic of seropositive anti-MOG neuromyelitis.

Uso del análisis de la capa de células ganglionares para el diagnóstico en la neuromielitis óptica anti-glucoproteína de la mielina del oligodendrocito

The case concerns a 26-year-old patient with bilateral recurrent optic neuritis episodes in the context of suspected neuromyelitis optica. In the first outbreak, she had greatly impaired visual acuity of the left eye, as well as seeing ganglion cell layer damage in both eyes in the optic coherence tomography, with evidence of a possible extensive lesion in the optic chiasma. Likewise, MRI with contrast showed a great involvement of the left optic nerve that compromises the chiasma increasing the suspicion of a neuromyelitis origin. Althogh the anti-myelin oligodendrocyte glycoprotein (MOG) and anti-AQP4 (aquaporin-4) antibodies were negative at first, bilateral involvement of the ganglion cells suggested an extensive lesion that is more characteristic of seropositive anti-MOG neuromyelitis.

Visual Outcome after Oral versus Intravenous Methylpredisolone Therapy for Bilateral Optic Neuritis in Adults

AbstractIntroduction: Bilateral optic neuritis in adults is rarer then unilateral optic neuritis. The purpose of this study was to know the clinical profile and to know the visual outcome of bilateral optic neuritis in adult patients after oral versus intravenous methylprednisolone therapy.Methods: A retrospective review of patients with bilateral optic neuritis referred to dr.Sardjito General Hospital, Yogyakarta from 2011-2014. The data consisted of bilateral optic neuritis, unassociated with other pathologic processes. There are two groups of patients: Group A taking oral methylprednisolone 1mg/kgBB and Group B received intravenous methylprednisolone (as ONTT guideline). Visual acuity, visual field with Goldmann Perimetry, RAPD (Relative Afferent Puppilary Defect), Ishihara test and direct ophthalmoscopy evaluation were recorded and analysed in both group at baseline, 1 week, 1 month and 3 months follow up. Results: Nineteen women and 9 men, with age range of 18-54 years old, had bilateral optic neuritis. The majority of the patients suffered from retrobulbar neuritis (43%), papilitis (39%) and neuroretinitis (18%). The average visual acuity before treatment in Group A was 0.22 ± 0.29 and in Group B had poorer average visual acuity 0.03±0.04 (p&gt;0.05). But the trend of visual recovery in Group B with visual acuity at baseline worsen, the recovery of visual acuity was faster and better at one week. After one month the visual acuity was comparable in both groups (p&gt;0.05).Conclusions: Visual improvement in early period of adult bilateral optic neuritis was similar after oral and intravenous methylprednisolone therapy.Keywords: Bilateral optic neuritis, methylprednisolone therapy, visual outcome

Trans-orbital sonography versus visual evoked potentials in acute demyelinating optic neuritis

Optic neuritis (ON) is an inflammatory demyelinating condition that causes acute - usually monocular - visual loss. It is highly associated with multiple sclerosis (MS). In general, ON is a clinical diagnosis based upon the history and examination findings. Objective: The aim was to assess the diagnostic accuracy of measuring optic nerve sheath diameter (ONSD) by ultrasound in acute optic neuritis. Methods: This is a prospective observational study with matched controls carried out on 25 patients and 25 controls. All patients presented with first attack of an acute demyelinating ON. Both patients and controls were submitted to clinical assessment, pattern and flash visual evoked potential and trans-orbital sonography (TOS) to measure the optic nerve sheath diameter (ONSD). Results: The ONSD was significantly thicker in patients with unilateral (0.6 ± 0.05 cm) and bilateral (0.6 ± 0.1 cm) optic neuritis compared to controls (0.52 ± 0.06 cm). P-value was < 0.001 and 0.04 respectively, with a cutoff value 0.57 cm. A significant negative correlation was found between the thickness of the ONSD and the visual acuity (r= −0.613, P-value <0.05). No correlation was found between the age of the patients and ONSD or between ONSD and latency of P-VEP. TOS showed 68% sensitivity and 88% specificity in diagnosing cases of ON. Conclusion: ONSD measured by TOS is a noninvasive, inexpensive bed-side test, which represent a supporting tool to confirm the clinical diagnosis of ON. Yet its sensitivity and specificity are lower than P-VEP.

A case of generalized myasthenia gravis with bilateral optic neuritis – A rare association

Myasthenia gravis (MG) is a relatively uncommon autoimmune disorder of neuromuscular junction characterized by fatigable muscle weakness, bulbar symptoms, and weakness of extraocular muscles with a significant diurnal variation. Among all other autoimmune disorders associated with optic neuritis, the association of MG with optic neuritis is very rare, with only a few cases have been reported till date. We present a rare case of 37 years old female who was admitted in November 2018 with generalized MG (seronegative) along with isolated bilateral optic neuritis, and the patient responded significantly to steroids, immunomodulators, and anticholinergics.

A Study of the Clinical Profile, Radiologic Features, and Therapeutic Outcomes in Neurosarcoidosis from Two Tertiary Care Centers in Southern India.

Sarcoidosis is an inflammatory granulomatous disease affecting multiple organ systems. Neurological manifestations are rare and seen in approximately 5% cases of sarcoidosis. They may commonly precede the diagnosis of sarcoidosis. Since there is paucity of Indian literature on this subject, we decided to review the clinical and radiological profile, laboratory abnormalities, treatment and long-term outcomes in our patients with neurosarcoidosis (NS). The study was done by retrospective review of medical records for all cases diagnosed as NS during the period Jan 2014-Jan 2018. These cases were classified as definite, probable, and possible NS, on the basis of established diagnostic parameters (Zajicek criteria). The follow-up record in these cases ranged from 6 months to 3 years, with special emphasis on monitoring the response to treatment and long-term disability. The cases showed varied clinical abnormalities and imaging findings. Cranial neuropathies and myelopathy were the most common clinical presentations. Optic neuritis was most common cranial neuropathy, followed by facial nerve palsy and lower cranial nerve palsies. Most common magnetic resonance imaging findings were T2 hyperintense parenchymal lesions and meningeal enhancement. There was strong correlation between baseline clinico radiological parameters and long-term outcomes, as evidenced by relatively poor prognosis seen in cases with bilateral optic neuritis, myelopathy and imaging evidence of hydrocephalus, or leptomeningitis. The diagnosis of NS requires a high degree of suspicion, coupled with exclusion of alternate diagnosis. It commonly precedes the onset of systemic sarcoidosis. Central nervous system involvement in sarcoidosis is associated with poor clinical outcomes.

Pigmentation of optic discs.

A 41-year-old female presented with perception of light in right eye and counting fingers vision in left eye since 6 months. She was a known case of autoimmune hepatitis and bilateral optic neuritis. Fundus examination revealed bilateral disc pallor with peripheral pigmentation of optic discs [Fig. 1a and b]. Optic disc pigmentation can occur in ocular abnormalities like optic disc hypoplasia, distended retinal vessels, iris transillumination defects, ptosis, nystagmus, and siderosis bulbi.[1234] Optic disc pigmentation after an episode of optic neuritis is rare. Optic disc pigmentation is a rare entity and ophthalmologists should rule out ocular and systemic associations.Figure 1: Fundus Photographs of right eye (a) and left eye (b) showing optic disc pigmentationDeclaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Beware of artifacts in orbital magnetic resonance imaging.

Orbital magnetic resonance imaging (MRI) is plagued by many artifacts, that sometimes closely mimic pathology.[1] We review the most common artifacts in clinical practice.[2] 2.1 Motion artifacts Optic neuritis is characterized by T2 hyperintensity of the optic nerves [Fig. 1a]. Similar changes can also be produced by motion artifacts [Fig. 1b], which are recognizable by the associated blurring of nerve outlines and ghosting [Fig. 1b and c]. Repeating the scan with the patient fixing the gaze removes these artifacts [Fig. 1d].Figure 1: (a) Bilateral optic neuritis, (b) Eye motion during scanning causes motion artifacts, (c) Motion also produces ghosting and blurring, (d) Repeat MRI of the patient in Figure 1b during eye fixation2.2 Partial volume artifacts Signal changes similar to optic neuritis [Fig. 2a] can occasionally be seen in normal optic nerves [Fig. 2b]. This occurs when the nerves are tortuous and the MR section includes adjacent fat, which artifactually increases signal in the nerve [Fig. 2c]. Fat suppressed sequences [Fig. 2d] are immune to this artifact.Figure 2: (a) Right optic neuritis, (b) Similar changes in both optic nerves produced by partial volume artifact, (c) Genesis of partial volume artifacts, (d) Fat saturated scan shows normal optic nervesSimilar phenomena can affect the extraocular muscles. Extraocular muscles are enlarged and show T2 hyperintensity in disorders such as orbital myositis [Fig. 3a] and thyroid ophthalmopathy. However, even normally, the lateral rectus muscles can appear bulky and hyperintense to rest of the muscles on coronal images [Fig. 3b]. Oblique orientation of lateral rectus muscles to the coronal plane makes them more susceptible to this phenomenon [Fig. 3c].Figure 3: (a) Orbital myositis, (b) Bulky, hyperintense lateral rectus muscles in a normal individual, (c) Obliquity of lateral rectus makes it more prone for partial volume artifact2.3 Susceptibility artifact Signal changes produced by disorders affecting the inferior rectus muscle, such as myositis [Fig. 4a] can occasionally be seen on fat saturated sequences, in individuals with metallic dental implants [Fig. 4b]. Disturbance of the magnetic field along the floor of the orbit by dental implants or air in the maxillary sinus interferes with fat saturation and creates a false appearance of edematous changes [Fig. 4c]. The artefact is recognizable as it extends beyond the muscle boundaries and is worst inferiorly. A similar artefact can be seen when the patient uses eye makeup (mascara) containing metallic iron particles.Figure 4: (a) Inferior rectus myositis, (b) Susceptibility artefact due to dental implants (*) causes hyperintensity of all tissues along the orbital floor, (c) Magnetic field disturbance by the metallic dental implant extends into the orbital floor (dotted line)2.4 Chemical shift artifact The appearance of tumor deposits along the optic nerve [Fig. 5a] can be seen even in normal individuals [Fig. 5b] as the so-called “Chemical shift artifact.” This artifact is typically seen at the interface between fluid and fat containing structures (such as optic nerve and retroorbital fat) as a band of dark signal intensity on one side (along the frequency encoding direction). This is caused by “mis-mapping” (shift) of the signal from retroorbital fat, in relation to the perioptic fluid [Fig. 5c]. Fat suppressed sequences [Fig. 5d] are immune to this artifact.Figure 5: (a) Leukemic deposits on left optic nerve, (b) Curvilinear bands of bright and dark signal along superior and inferior aspects of optic nerves in a normal individual, (c) Illustration of chemical shift artifact, (d) Fat saturated scan in the same individual shows normal optic nervesThis artifact is also seen at the margin of fat containing structures surrounded by fluid (e.g., silicone oil in the globe or intracranial lipomas) and fluid containing structures surrounded by fat (e.g., cysts or hemangiomas within the retroorbital fat). Presence of this artifact gives vital clues in the diagnosis of these conditions. 2.5 Financial support and sponsorship Nil. 2.6 Conflicts of interest There are no conflicts of interest.

Pediatric anti-N-methyl-D-aspartate receptor encephalitis and bilateral optic neuritis: An updated review

We present the case report of a 6-year-old girl with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis associated with bilateral optic neuritis. She initially presented with disturbing behaviors and gait impairments and was hospitalized in the context of meningoencephalitis, without agent isolation and with inconclusive laboratory tests. After discharge, she noted a loss of vision with impaired color sensation and returned to the emergency department. Her best-corrected visual acuity was 20/400 in both eyes, and fundoscopy revealed bilateral optic disc edema. She was hospitalized once again. Anti-NMDAR antibodies were detected in serum and cerebrospinal fluid. The patient was successfully treated with a pulse of methylprednisolone, followed by a tapering regimen of prednisolone. She recovered to 20/20 vision in the right eye and left eye. Our report highlights additional aspects of anti-NMDAR encephalitis in children and suggests that the disease could present atypical visual manifestations, which requires multidisciplinary approaches.

Atypical Multiple Sclerosis with Antibody to MOG

We report a case of a young female who had magnetic resonance imaging (MRI) brain lesions typical of multiple sclerosis (MS) with cerebrospinal fluid (CSF) oligoclonal bands (OCBs) and definite multiple sclerosis based on revised McDonald criteria; however, she also had atypical features of mild pleocytosis, brainstem and cerebellar peduncle involvement apart from opticospinal (OS) involvement. She also turned out to be positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibody; hence, she was diagnosed with atypical multiple sclerosis. This case highlights when to suspect atypical MS and its management approach. Typical MS cases are largely anti-MOG-negative. In a study of 50 Japanese cases, with anti-aquaporin 4 (AQP4)-immunoglobulin (IgG)-negative OSMS, just 2 were MOG-IgG-positive, but they had some features atypical for MS, such as bilateral optic neuritis, longitudinally extensive transverse myelitis, or moderate pleocytosis. In another study, antibodies to MOG were found in about 5% (5/104) of preselected adult patients with MS. Patients with MS with antibodies to MOG showed typical MS lesions on brain MRI with concomitant severe brainstem and spinal cord involvement and had a severe disease course with high relapse rates. In conclusion, any patient showing typical MS lesions on brain MRI with OCB present in CSF but has atypical features like mild pleocytosis with brainstem, cerebellar, or OS involvement should also be tested for autoantibodies to MOG, and if positive, then he/she would require aggressive treatment approach in the form of plasma exchange, if resistant to pulse steroid therapy, followed by either rituximab or natalizumab rather than trying other disease modifying therapies (DMTs).

Myelin Oligodendrocyte Glycoprotein (MOG) Antibody-Associated CNS Demyelination: Clinical Spectrum and Comparison with Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorder.

The clinical phenotypes of myelin oligodendrocyte glycoprotein (MOG) antibody disease, its disease course, and treatment are poorly understood and much work needs to be done towards this. To characterize the clinico-radiologic spectrum and treatment outcomes of MOG antibody disease and differentiate it from aquaporin-4 (AQP-4) antibody positive neuromyelitis optica spectrum disorders (NMO-SD). A single-center, observational study from Western India during 2017-2019, of 48 patients with either MOG antibody positive (21 patients) or AQP-4 antibody positive (27 patients) central nervous system demyelination. MOG antibody group had median age 32.2 years, no gender bias, median disease duration 40 months, relapses in 9 patients (43%), and median 2.5 (1-16) episodes per patient. Onset phenotypes included isolated bilateral optic neuritis (ON) (43%), isolated unilateral ON (19%), acute brainstem syndrome (19%), simultaneous ON with myelitis (9%), isolated myelitis (5%), and acute disseminated encephalomyelitis optic neuritis (ADEM-ON) (5%). Characteristic neuroimaging abnormalities were anterior segment longitudinally extensive ON, upper brainstem, and thoracic cord involvement (both short and long segment lesions). Most patients (86%) responded well to steroids, only 3/21 required rescue immunotherapy. In total, 6 out of 46 eyes affected developed permanent visual disability, while one patient had motor disability. The features differentiating MOG from AQP-4 antibody group were: no female predilection, preferential optic nerve involvement, characteristic neuroimaging abnormalities, and favorable therapeutic response and outcome. MOG disease commonly presents as severe ON, myelitis, acute brainstem syndrome, ADEM or their combinations. Early identification, treatment, and maintenance immunosuppression are necessary. It can easily be differentiated from NMO-SD using clinico-radiological features and therapeutic response.

Does area postrema syndrome occur in myelin oligodendrocyte glycoprotein-IgG-associated disorders (MOGAD)?

Myelin oligodendrocyte glycoprotein-IgG is a biomarker associated with CNS demyelinating diseases.1,2 MOGAD and aquaporin-4-IgG–positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD) have overlapping clinical features including optic neuritis and myelitis. However, there are several clinical and radiologic distinguishing features of MOGAD including lack of female predominance, higher incidence of acute disseminated encephalomyelitis (ADEM), higher proportion of bilateral optic neuritis, and T2-signal confined to gray matter and conus involvement in myelitis.1,3,4

Teaching NeuroImages: Substantia nigra T2 hyperintensities in a man with Leber hereditary optic neuropathy

A 29-year-old man with alcoholism presented with sudden progressive central visual loss in the right eye. Visual acuity was 20/300 (right) and 20/20 (left). Other findings included right relative afferent pupillary defect and bilateral hyperemic nonedematous optic discs concerning for OD retrobulbar optic neuritis. MRI head and orbit revealed symmetric T2 hyperintensities in the substantia nigra, without optic nerve hyperintensities (figure). Subsequently he lost vision in his left eye. Given that his maternal uncle developed bilateral optic neuritis in his 20s, genetic testing for Leber hereditary optic neuropathy was performed, finding a point mutation (m.11778G>A) in mitochondrially encoded NADH dehydrogenase 4. The unusual gray matter hyperintensities in this case favored a metabolic rather than demyelinating etiology.