Optic neuritis (ON) is a rare neurological complication of measles infection. Little is known about measles-associated retrobulbar ON. Here, we report a distinct patient with unilateral retrobulbar ON due to measles infection. A 26-year-old woman developed maculopapular rash and Koplik spots. On the following 3 days, she noticed blurred vision in the left eye. A Goldmann visual field test showed inferior nasal quadrantanopsia in the left eye. Visual acuity was 20/20 in OD and 20/100 in OS. Pupillary size was 2.0 mm in the right eye and 4.0 mm in the left eye. Light reflexes were slightly sluggish in the left eye. Ophthalmoscopy showed mild pallor of the left optic disc. Central critical flicker fusion frequency (CFF) was 40.7 Hz in the right eye and 10.1 Hz in the left eye (normal =29.0). Visual evoked potentials showed that P100 latencies were delayed on the left side (133 ms). Brain and spinal cord MRI was normal. Orbital MRI displayed abnormal enhancement in the left optic nerve. Serum and cerebrospinal fluid IgG titers of anti-measles antibodies were increased. Left measles-associated ON was diagnosed. Methylprednisolone pulse therapy followed by oral administration of prednisolone ameliorated visual acuity, visual field and CFF. The neuroophthalmic profile of our patient indicated that measles infection triggered isolated retrobulbar ON, leading to unusual visual deficits. Thus, physicians should pay more attention to variable patterns of measles-associated ON.
Measles virus; Optic nerve MRI; Quadrantanopsia; Retrobulbar optic neuritis
In a single-blind controlled clinical trial patients with optic neuritis caused by demyelination were given a single retrobulbar injection of triamcinolone. Though the treated group showed a trend towards more rapid recovery of vision than the controls, there was no significant difference in visual acuity, colour vision, or visual fields during the first six months after treatment. We conclude that routine use of corticosteroids is not justified in unilateral optic neuritis when vision in the other eye is good. Shortening the period of visual disability in bilateral disease or unilateral disease when vision in the other eye is poor, however, may be justifiable.
A patient with established retrobulbar neuritis and Uhthoff's phenomenon who claimed that his visual acuity improved after drinking beer was assessed by detailed quantitative psychophysical tests. Studies of electrophysiological responses and biochemical levels of blood serum before and after drinking on several occasions were also made. The results of tests of contrast sensitivity, spectral sensitivity, flicker sensitivity, and visually evoked potential confirmed his observation. Some mechanisms for this phenomenon are considered.
Aim. To show that high-dose corticosteroids may prevent visual loss in patients with optic neuritis (ON) treated at the prodromal, hyperacute, phase of retrobulbar pain. Method. Prospective case series: patients were recruited with a history of ON associated with pain. The patients were advised to report immediately to the investigators should the pain recur in either eye. Where possible, orbital magnetic resonance imaging (MRI) was performed to confirm a recurrence of ON and treatment with high-dose corticosteroids was commenced. Visual function and the patient's subjective account were monitored. Results. Eight patients (including cases of MS, CRION and NMO) presented in the hyperacute phase. MRI confirmed optic nerve inflammation in 5/5. Treatment was commenced immediately, and, in all cases, no visual loss ensued. Conclusion. MRI can be used to confirm acute optic neuritis prior to visual loss in the hyperacute phase. We suggest that treatment with high-dose corticosteroids may abort the attack and prevent loss of vision in patients with ON who are treated at the onset of pain. This has potential implications for the management of acute ON and also for our understanding of the pathogenesis and potential therapeutic targets in the neuroinflammatory conditions associated with ON.
To describe a case of retrobulbar optic neuritis that presented within 3 weeks of adalimumab treatment initiation.
This index case was evaluated with visual field testing, brain magnetic resonance imaging, lumbar puncture, and laboratory evaluation, and treated with intravenous methylprednisolone followed by a steroid taper.
Our patient made a full visual recovery, but was found to have extensive T2/FLAIR foci of hyperintensities that enhanced and had restricted diffusion on magnetic resonance imaging (MRI). Six months later, these demyelinating lesions still persisted and our patient was initiated on immunomodulatory treatment.
With the extensive burden of disease at presentation and persistence of lesions on follow-up MRI, this unusual case seems to suggest an unmasking of an underlying demyelinating process by adalimumab. The clinician should be mindful of this association and monitor for any manifestations and treat appropriately.
Tumor necrosis factor; Optic neuritis; Multiple sclerosis; Adalimumab
To report two cases of optic neuritis with onset less than 24 hours following measles-rubella (MR) vaccination.
Two teenage patients developed acute optic neuritis 6 to 7 hours after MR booster vaccination. The first patient demonstrated bilateral papillitis and severe visual loss but improved significantly with pulse intravenous steroid therapy with methylprednisolone 500 mg/day. The second patient had unilateral retrobulbar optic neuritis and demonstrated excellent visual recovery without intervention.
Acute optic neuritis is a rare complication of MR vaccination and may occur early after immunization.
A 27-year-old Thai male presented with progressive visual loss and a membrane-like floater in the
right eye that had persisted for 1 month. He had a history of eating raw foods, including snails.
His initial visual acuity was counting fingers at 1 ft and he had a relative afferent pupillary
defect. A movable larva with subretinal tracks was found in the subretinal space near a normal optic
disc. Visually evoked potentials showed delayed latency, which indicated secondary retrobulbar optic
neuritis. A diode laser was directly applied to the motile worm. The patient was subsequently
prescribed oral prednisolone and albendazole. After treatment, his visual acuity was slightly
improved at 2/60. Ocular manifestation is a very rare event resulting from parasitic infection. In
only 1.1% of angiostrongyliasis cases is an Angiostrongylus cantonensis
larva identified in the eye. Ocular angiostrongyliasis with optic neuritis may be secondary to
mechanical injury and/or inflammatory reactions. Steroid treatment is recommended, although most
patients have only slight visual improvement after treatment.
Angiostrongylus cantonensis; intraocular; ocular angiostrongyliasis; parasitic infection
Although optic neuritis (ON) is a defining feature of neuromyelitis optica (NMO), appropriate animal models of NMO ON are lacking. Most NMO patients are seropositive for immunoglobulin G autoantibodies (NMO-IgG) against the astrocyte water channel aquaporin-4 (AQP4).
Several approaches were tested to develop a robust, passive-transfer mouse model of NMO ON, including NMO-IgG and complement delivery by: (i) retrobulbar infusion; (ii) intravitreal injection; (iii) a single intracranial injection near the optic chiasm; and (iv) 3-days continuous intracranial infusion near the optic chiasm.
Little ON or retinal pathology was seen using approaches (i) to (iii). Using approach (iv), however, optic nerves showed characteristic NMO pathology, with loss of AQP4 and glial fibrillary acidic protein immunoreactivity, granulocyte and macrophage infiltration, deposition of activated complement, demyelination and axonal injury. Even more extensive pathology was created in mice lacking complement inhibitor protein CD59, or using a genetically modified NMO-IgG with enhanced complement effector function, including significant loss of retinal ganglion cells. In control studies, optic nerve pathology was absent in treated AQP4-deficient mice, or in wild-type mice receiving control (non-NMO) IgG and complement.
Passive transfer of NMO-IgG and complement by continuous infusion near the optic chiasm in mice is sufficient to produce ON with characteristic NMO pathology. The mouse model of NMO ON should be useful in further studies of NMO pathogenesis mechanisms and therapeutics.
NMO; Neuroinflammation; Mouse models; Aquaporin; Astrocyte
Microcystic macular edema (MME) and inner nuclear layer thickening (INL) were described in multiple sclerosis (MS) and neuromyelitis optica (NMO) patients using optical coherence tomography (OCT). The cause of these findings is currently unknown and a relation to inflammatory or degenerative processes in the optic nerve is discussed.
The aim of our study was to investigate whether INL thickening and MME are related to optic neuritis (ON) in various neuro-inflammatory disorders causingON: MS, NMO and chronic inflammatory optic neuropathy.
We retrospectively analyzed data from 216 MS patients, 39 patients with a clinically isolated syndrome, 20 NMO spectrum disorder patients, 9 patients with chronic inflammatory optic neuropathy and 121 healthy subjects. Intra-retinal layer segmentation was performed for the eyes of patients with unilateral ON. Scanning laser ophthalmoscopy (SLO) images were reviewed for characteristic ocular fundus changes.
Intra-retinal layer segmentation showed that eyes with a history of ON displayed MME independent INL thickening compared to contralateral eyes without previous ON. MME was detected in 22 eyes from 15 patients (5.3% of all screened patients), including 7 patients with bilateral edema. Of these, 21 had a prior history of ON (95%). The SLO images of all 22 MME-affected eyes showed crescent-shaped texture changes which were visible in the perifoveal region. A second grader who was blinded to the results of the OCT classified all SLO images for the presence of these characteristic fundus changes. All MME eyes were correctly classified (sensitivity = 100%) with high specificity (95.2%).
This study shows that both MME and INL thickening occur in various neuro-inflammatory disorders associated with ON. We also demonstrate that detection and analysis of MME by OCT is not limited to B-scans, but also possible using SLO images.
The effect of IgG immunoadsorption upon the course of chronic experimental allergic neuritis (EAN) is described. Miniature membrane plasma separators coupled with a Protein A (PA)-Sepharose immunoadsorbent column were used to perform upon conscious rabbits 5 IgG immunoadsorption treatments over 6 days. Quantitation of anti-myelin IgG and IgM by ELISA revealed that 55-65% of plasma IgG was removed per treatment. Rapid post-treatment antibody rebound was observed for anti-myelin IgG although no antibody overshoot above control levels could be observed. Anti-myelin IgM levels remained relatively unaffected by PA immunoadsorption. Comparisons of clinical scores between control and treatment animals showed that IgG immunoadsorption was significantly beneficial (day 1 post-treatment p less than 0.001; day 2 post-treatment p less than 0.05). However, rapid relapse was observed in all treatment animals such that by day 3 post-treatment no significant clinical difference between control and treatment groups could be observed. IgG immunoadsorption suppresses the clinical progression of chronic EAN in a manner similar to that seen with plasma exchange. This finding suggests that antibody modulates early disease pathogenesis.
Three patients with chronic renal failure treated by haemodialysis developed acute asymmetrical sensory and motor neuropathies when ultrafiltration was induced to treat oedema. The neuropathies were characteristic of acute mononeuritis multiplex rather than uraemic polyneuritis, and we give our reasons for believing that they were not caused by toxic uraemic metabolites but by an ischaemic process due to vasoconstriction resulting from ultrafiltration.
Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are neurodegenerative diseases with characteristic inflammatory demyelination in the central nervous system, including the optic nerve. Neuronal and axonal damage is considered to be the main cause of long-term disability in patients with MS. Neuronal loss, including retinal ganglion cell (RGC) apoptosis in eyes with optic neuritis (ON), also occurs in EAE. However, there is significant variability in the clinical course and level of neuronal damage in MS and EAE. The current studies examine the mechanisms and kinetics of RGC loss in C57/BL6 mice immunized with myelin oligodendrocyte glycoprotein to induce a chronic EAE disease. Clinical progression of EAE was scored daily and vision was assessed by optokinetic responses. At various time points, RGCs were counted and optic nerves were examined for inflammatory cell infiltration. Almost all EAE mice develop ON by day 15 post-immunization; however, RGC loss is delayed in these mice. No RGC loss is detected 25 days post-immunization, whereas RGC numbers in EAE mice significantly and progressively decrease compared to controls from 35 to 50 days post-immunization. The delayed time course of RGC loss is in stark contrast to that reported in relapsing EAE, as well as in rats with chronic EAE. Results suggest that different clinical disease courses of optic nerve inflammation may trigger distinct mechanisms of neuronal damage, or RGCs in different rodent strains may have variable resistance to neuronal degeneration.
optic neuritis; multiple sclerosis; EAE; RGC; neurodegeneration
A Chinese rhesus macaque infected with the pathogenic CCR5-tropic clade C simian-human immunodeficiency virus, SHIV-1157ipd3N4, had persistent viremia, depletion of CD4+ T cells to <200 cells/μl, opportunistic infections, coagulopathy and gradual development of bilateral blindness. MRI revealed marked thickening of both optic nerves. Histopathological evaluation showed diffuse cellular infiltration at necropsy, and a focus of infected cells. This is the first report of CNS pathology following chronic infection with an obligate R5 SHIV.
R5 SHIV; neuroAIDS; optic neuropathy
A 25-year-old housewife presented with a burning sensation over both legs for the past 15 months, and fever with weight loss for the past six months. She had noticed a lump in her left breast one month ago. Examination revealed hyperaesthesia and allodynia over the lower limbs. Nerve conduction studies confirmed the presence of sensory neuropathy. Nerve biopsy was suggestive of a chronic axonopathy. Subsequently sputum as well as aspirate from the breast lump tested positive for acid fast bacilli. Treatment with anti-tubercular therapy resulted in full recovery. Peripheral neuropathy is a unique and unusual presentation of tuberculosis.
peripheral neuropathy; disseminated tuberculosis; sensory polyneuropathy
Optic neuritis (ON) is defined as an inflammation of the optic nerve and provides a useful model for studying the effects of inflammatory demyelination of white matter. The aim of this study was to assess the diffusion changes in both the optic nerve and optic radiation in patients with acute and chronic ON using diffusion tensor (DT) MRI.
33 patients with idiopathic demyelinating optic neuritis (IDON) and 33 gender- and age-matched healthy controls were examined with DT-MRI and with T1 and T2 weighted MRI.
Compared with controls, both first-episode and recurrent patients with IDON in the acute stage showed significantly increased radial diffusivity (λ⊥) and decreased mean fractional anisotropy (FA) in the affected nerves. Reduced FA, increased λ⊥, mean diffusivity (MD) and axial diffusivity (λ∥) were determined in patients with subacute IDON. We found no significant difference in the directional diffusivity of optic radiation in patients whose disease had lasted less than 1 year compared with healthy controls. However, significant changes in the FA and λ⊥ of the optic radiation were detected in patients with disease duration of more than 1 year.
These results show the great potential and capacity of DT-MRI measures as useful biomarkers and indicators for the evaluation of myelin injury in the visual pathway.
Optic neuritis is associated with neurodegeneration leading to chronic impairment of visual functions.
This study investigated whether early treatment with interferon beta (IFN-β) slows retinal nerve fibre layer (RNFL) thinning in clinically isolated optic neuritis.
Twenty patients with optic neuritis and visual acuity decreased to ≤0.5 (decimal system) were included into this prospective, open-label, parallel group 4-month observation. After methylprednisolone pulse therapy, 10 patients received IFN-β from week 2 onwards. This group was compared to 10 patients free of any disease modifying treatment (DMT). The parameter of interest was change in RNFL thickness assessed at baseline and at weeks 4, 8, and 16. Changes in visual acuity, visual field, and visual evoked potentials (VEPs) served as additional outcome parameters.
RNFL thinning did not differ between the groups with a mean reduction of 9.80±2.80 µm in IFN-β-treated patients (±SD) vs. 12.44±5.79 µm in patients who did not receive DMT (baseline non-affected eye minus affected eye at week 16; p = 0.67, t-test, 95% confidence interval: −15.77 to 10.48). Parameters of visual function did not show any differences between the groups either.
In isolated optic neuritis, early IFN-β treatment did not influence RNFL thinning nor had it any effect on recovery of visual functions.
The authors present a case of optic neuritis in an adult patient who had been self-prescribing extraordinarily large dosages of chloramphenicol for chronic prostatitis over several years. The visual symptoms resolved upon cessation of the drug and prescription of B group vitamins. Chloramphenicol optic neuritis has not been described in the literature for over 20 years and previously predominantly in children with cystic fibrosis.
Pancreatic neuritis is a histopathological hallmark of pancreatic neuropathy and correlates to abdominal neuropathic pain sensation in pancreatic adenocarcinoma (PCa) and chronic pancreatitis (CP). However, inflammatory cell subtypes that compose pancreatic neuritis and their correlation to the neuropathic pain syndrome in PCa and CP are yet unknown.
Inflammatory cells within pancreatic neuritis lesions of patients with PCa (n = 20) and CP (n = 20) were immunolabeled and colorimetrically quantified with the pan-leukocyte marker CD45, with CD68 (macrophages), CD8 (cytotoxic T-lymphocytes), CD4 (T-helper cells), CD20 (B-lymphocytes), NCL-PC (plasma cells), neutrophil elastase, PRG2 (eosinophils), anti-mast cell (MC) tryptase and correlated to pain sensation. Perineural mast cell subtypes were analyzed by double immunolabeling with MC chymase. Expression and neural immunoreactivity of protease-activated receptor type 1 (PAR-1) and type 2 (PAR-2) were analyzed in PCa and CP and correlated to pain status of the patients.
In PCa and CP, nerves were predominantly infiltrated by cytotoxic T-lymphocytes (PCa: 35% of all perineural inflammatory cells, CP: 33%), macrophages (PCa: 39%, CP: 33%) and MC (PCa: 21%, CP: 27%). In both entities, neuropathic pain sensation was associated with a specific increase of perineural MC (PCa without pain: 14% vs. PCa with pain: 31%; CP without pain: 19% vs. CP with pain: 34%), not affecting the frequency of other inflammatory cell subtypes. The vast majority of these MC contained MC chymase. PAR-1 and PAR-2 expression did not correlate to the pain sensation of PCa and CP patients.
Pancreatic neuritis in PC and CP is composed of cytotoxic T-lymphocytes, macrophages and MC. The specific enrichment of MC around intrapancreatic nerves in neuropathic pain due to PCa and CP suggests the presence of MC-induced visceral hypersensitivity in the pancreas. Therefore, pancreatic and enteric neuropathies seem to share a similar type of neuro-immune interaction in the generation of visceral pain.
Takayasu arteritis (TA) is a chronic vasculitis that affects the aortic arch and its primary branches. Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Patients diagnosed with both TA and UC have rarely been reported. The pathogenesis of TA and UC is uncertain, but cell-mediated mechanisms play an important role in both diseases, and a genetic factor is thought to have an effect on the coincidence of these two diseases. We herein report a 38-year-old female with TA who had a history of UC with optic neuritis. We believe that this is the first case of the coexistence of TA and UC in Korea.
Takayasu arteritis; Colitis, ulcerative; Optic neuritis
To determine the clinical features, diagnosis and treatment of the primary Sjögren syndrome (SS) related optic neuritis.
The clinical data of 8 patients (12 eyes) with primary SS related optic neuritis were analyzed retrospectively.
Eight of 128 consecutive patients with optic neuritis resulted from varied causes fulfilled the diagnostic criteria for the primary SS. They presented initially with the signs and symptoms of non-specific optic neuritis, and 5 patients presenting without dryness showed a chronic inflammation of submandibular gland or parotid gland, and lymphocyte infiltration was demonstrated by labial gland biopsy in 2 patients. There were serum positive titers for anti-Sjögren syndrome A (SSA) in 7 patients and anti-Sjögren syndrome B (SSB) in 8 patients. Anti-aquaporin-4 (AQP4) antibody was negative in all the 8 patients. Both glucocorticoids and immunosuppressive agent were administered, and visual acuity elevated in 8 eyes (66.7%), 3 patients (37.5%) recurred in the follow-up.
Primary SS related optic neuritis is less common and easily misdiagnosed. The conventional therapies for optic neuritis could not control the recurrence.
optic neuritis; primary Sjögren's syndrome; anti-aquaporin-4
Systemic Sclerosis (SSc) is a connective tissue disorder which involves multiple systems in a chronic progressive manner. Micro–angiopathic haemolytic anaemia is a distinguished feature of “scleroderma renal crisis”, which is manifested by severe hypertension, a rapidly progressing renal dysfunction and hyperreninaemia and is seen in patients with an early, diffuse form of the disease. A nervous system involvement is rare, though entrapment neuropathies have been reported. Who presented with a sequential loss of vision in both eyes; due to retinal vasculitis in right eye and optic nerve demyelination in the left eye. She also had severe Coombs’ negative haemolytic anaemia in absence of any renal dysfunction or hypertension. Both the ophthalmologic and the haematologic manifestations are very rare and both responded well to oral prednisolone therapy.
Systemic sclerosis; Retinal vasculitis; Optic neuritis; Autoimmune haemolytic anaemia
Vestibular neuritis (VN) is commonly diagnosed by demonstration of unilateral vestibular failure, as unilateral loss of caloric response. As this test reflects the function of the superior part of the vestibular nerve only, cases of pure inferior nerve neuritis will be lost.
We describe three patients with symptoms suggestive of VN, but normal calorics. All 3 had unilateral loss of vestibular evoked myogenic potential. A slight, asymptomatic position dependent nystagmus, with the pathological ear down, was observed.
We believe that these patients suffer from pure inferior nerve vestibular neuritis.
Measles-virus-specific IgG was measured in the serum of 100 patients who had presented with optic neuritis (ON) during 1960-74. When reviewed 41 of them were found to have developed definite symptoms and signs of multiple sclerosis (MS), their serum containing significantly higher titres of the antibody than sera from either the rest of the patients or a group of normal healthy controls. In a few patients from whom cerebrospinal fluid (CSF) was obtained in the acute phase of ON, titres of measles IgG in the serum was higher in those in whom the antibody was detected in the CSF than the serum of patients without CSF antibody.