Retinal changes associated with multivitamin deficiency before and after supplementation.

BACKGROUND: Nutritional visual defects are apparently uncommon nowadays in developed nations. Retinal change-related visual defects caused by hypovitaminoses may be underdiagnosed. AIM OF THE STUDY: To investigate the retinal structural and functional changes in a patient with multivitamin deficiency before and during vitamin supplementation. METHODS: A 51-year-old female had been on vegetarian diet as a child, and on restrict vegan diet during the last 2 years, developing severe bilateral deterioration of visual function and polyneuropathy. Blood test revealed low levels of vitamin A, B6 and D. The patient underwent examinations with optical coherence tomography (OCT), computerized visual field examination (VF), electroretinography (ERG), visual evoked potentials (VEP) and neurography before and after vitamin supplementation. RESULTS: Visual acuity (VA) was 20/1000 and VF examination showed central scotoma in both eyes. Color vision was significantly affected. Full-field ERG showed normal rod and cone function, but a clearly reduced central peak was registered in multifocal ERG (mf-ERG), indicating impaired fovea function. VEP showed delayed latency and low amplitude of P100 in both eyes. Neurography showed sensory polyneuropathy. OCT showed significant thinning of macular ganglion cell plus inner plexiform layer (GCIPL) with rapid progression. Retinal nerve fiber layer (RNFL) was preserved and normal, which is in contrast to neuroinflammatory conditions. After 2.5 years of multivitamin supplementation, the visual functions were improved. GCIPL thickness was stable without further deterioration. CONCLUSIONS: Multivitamin deficiency results in progressive thinning of GCIPL with severe visual deterioration. In contrast to neuroinflammation, RNFL is preserved and normal. Stabilized GCIPL during vitamin supplementation was associated with improved visual function. OCT provides a sensitive and objective measure for differential diagnosis, monitoring retinal change and response to therapy.

Retinal thinning and brain atrophy in early MS and CIS.

BACKGROUND: Optical coherence tomography (OCT) could be complementary to magnetic resonance imaging (MRI) of the brain in monitoring course of multiple sclerosis (MS) and clinically isolated syndrome (CIS). Thinning of neurons in ganglion cell-inner plexiform layer (GCIPL) measured by OCT is assumed to be associated with brain atrophy. OBJECTIVES: To evaluate association of GCIPL with brain parameters detected by quantitative MRI (qMRI) and MR-spectroscopy (MRS) in early MS and CIS. METHODS: Seventeen newly diagnosed MS and 18 CIS patients were prospectively included. The patients were assessed at baseline as well as at 1 year follow-up by OCT, qMRI and MRS. Brain parenchymal and myelin volumes (BPV, MYV respectively) and the corresponding fractions (BPF, MYF) were measured with qMRI. Metabolites including myo-inositol (myo-Ins) were measured in the normal-appearing white matter (NAWM) using MRS. T-tests and ANOVA were used to analyze group differences, and linear regression models to evaluate association of GCIPL with BPV, MYV and myo-Ins after correlation analysis. RESULTS: Disease activity reflected by lesions on MRI and presence of CSF oligoclonal IgG bands were more prominent in MS compared to CIS. GCIPL, BPV, MYV, BPF and MYF were reduced, while concentration of myo-Ins was increased in MS compared to CIS. Follow-up showed consistency of thinner GCIPL in MS compared to CIS. GCIPL thinning correlated with reduced BPV and MYV (P < .05 for both), but with increased myo-Ins (P < .01). CONCLUSIONS: Significant GCIPL thinning occurs in early MS and is associated with enhanced brain inflammation and atrophy.

Acute optic neuritis: retinal ganglion cell loss precedes retinal nerve fiber thinning.

Optic neuritis (ON) causes axonal loss as reflected by thinning of retinal nerve fiber layer (RNFL) and can be tracked by optical coherence tomography (OCT) about 6 months after ON onset, when swelling of optic nerve head (ONH) has vanished. Changes of macular ganglion cell layer (GCL) thickness provide another window to track the disease process in ON. GCL thinning over time in relation to RNFL change after ON remains elusive. Using OCT, we followed 4 patients with acute unilateral isolated ON for more than 9 months. A diagnosis of multiple sclerosis (MS) was established in all 4 patients. First follow-up was 2-3 weeks after ON onset, and thereafter every 2-3 months. RNFL swelling peaked during first month after acute ON, followed by rapidly reduced swelling (pseudoatrophy) during following 2 months, and thereafter successively vanished 6 months after ON onset. GCL thinning was observed 1-3 months after ON onset, i.e. already during optic disk swelling and before real RNFL thinning. The results imply that quantifying GCL thickness provides opportunities to monitor early axonal loss and ON-to-MS progression, and facilitates distinguishing real atrophy from pseudoatrophy of RNFL after acute ON.

Longitudinal Optical Coherence Tomography Measurement of Retinal Ganglion Cell and Nerve Fiber Layer to Assess Benign Course in Multiple Sclerosis.

A benign form of multiple sclerosis (BMS) is not easily diagnosed, but changes of the retinal ganglion cell layer-inner plexiform layer (GCL-IPL) and retinal nerve fiber layer (RNFL) may be sensitive to the disease. The aim of this study was to use optical coherence tomography (OCT) to investigate longitudinal changes of GCL-IPL and RNFL in BMS. Eighteen patients with BMS and 22 healthy control (HC) subjects were included, with a mean follow-up period of 32.1 months in BMS and 34.3 months in HC. Mean disease duration in BMS was 23.3 years, with 14 patients left untreated. Unilateral optic neuritis (ON) was found in eight patients. Non-ON eyes showed thinner GCL-IPL layer in the BMS group relative to HC (p < 0.001). The thinning rate of GCL-IPL in non-ON BMS, however, was -0.19 ± 0.15 µm/year vs. 0 ± 0.11 µm/year for HC (p = 0.573, age-adjusted). Thinning rate of RNFL in non-ON BMS was -0.2 ± 0.27 µm/year vs. -0.05 ± 0.3 µm/year for HC (p = 0.454, age adjusted). Conclusions: Thinning rate of the GCL-IPL and RNFL in BMS is similar to the healthy population but differs from the thinning rate in relapsing-remitting MS, presenting a non-invasive OCT-based criterion for assessing a benign course in multiple sclerosis.

The Importance of Optical Coherence Tomography in the Diagnosis of Atypical or Subclinical Optic Neuritis: A Case Series Study.

Background: Optic neuritis (ON) is an inflammatory condition of the optic nerve. ON is associated with development of demyelinating diseases of the central nervous system (CNS). CNS lesions visualized by magnetic resonance imaging (MRI) and the finding of oligoclonal IgG bands (OB) in the cerebrospinal fluid (CSF) are used to stratify the risk of MS after a "first" episode of ON. However, the diagnosis of ON in absence of typical clinical manifestations can be challenging. Methods and Materials: Here we present three cases with changes in the optic nerve and ganglion cell layer in the retina over the disease course. (1) A 34-year-old female with a history of migraine and hypertension had suspect amaurosis fugax (transient vision loss) in the right eye. This patient developed MS four years later. Optical coherence tomography (OCT) showed dynamic changes of the thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) over time. (2) A 29-year-old male with spastic hemiparesis and lesions in the spinal cord and brainstem. Six years later he showed bilateral subclinical ON identified using OCT, visual evoked potentials (VEP) and MRI. The patient fulfilled diagnosis criteria of seronegative neuromyelitis optica (NMO). (3) A 23-year-old female with overweight and headache had bilateral optic disc swelling. With OCT and lumbar puncture, idiopathic intracranial hypertension (IIH) was excluded. Further investigation showed positive antibody for myelin oligodendrocyte glycoprotein (MOG). Conclusions: These three cases illustrate the importance of using OCT to facilitate quick, objective and accurate diagnosis of atypical or subclinical ON, and thus proper therapy.

Inventory study of an early pandemic COVID-19 cohort in South-Eastern Sweden, focusing on neurological manifestations.

BACKGROUND: Neurological manifestations in patients with COVID-19 have been reported previously as outcomes of the infection. The purpose of current study was to investigate the occurrence of neurological signs and symptoms in COVID-19 patients, in the county of Östergötland in southeastern Sweden. METHODS: This is a retrospective, observational cohort study. Data were collected between March 2020 and June 2020. Information was extracted from medical records by a trained research assistant and physician and all data were validated by a senior neurologist. RESULTS: Seventy-four percent of patients developed at least one neurological symptom during the acute phase of the infection. Headache (43%) was the most common neurological symptom, followed by anosmia and/or ageusia (33%), confusion (28%), hallucinations (17%), dizziness (16%), sleep disorders in terms of insomnia and OSAS (Obstructive Sleep Apnea) (9%), myopathy and neuropathy (8%) and numbness and tingling (5%). Patients treated in the ICU had a higher male presentation (73%). Several risk factors in terms of co-morbidities, were identified. Hypertension (54.5%), depression and anxiety (51%), sleep disorders in terms of insomnia and OSAS (30%), cardiovascular morbidity (28%), autoimmune diseases (25%), chronic lung diseases (24%) and diabetes mellitus type 2 (23%) founded as possible risk factors. CONCLUSION: Neurological symptoms were found in the vast majority (74%) of the patients. Accordingly, attention to neurological, mental and sleep disturbances is warranted with involvement of neurological expertise, in order to avoid further complications and long-term neurological effect of COVID-19. Furthermore, risk factors for more severe COVID-19, in terms of possible co-morbidities that identified in this study should get appropriate attention to optimizing treatment strategies in COVID-19 patients.

Predictors of Early Neurological Deterioration and Functional Outcome in Acute Ischemic Stroke: The Importance of Large Artery Disease, Hyperglycemia and Inflammatory Blood Biomarkers.

Background: Early neurological deterioration (END) in acute ischemic stroke (AIS) can be associated with poor outcome. The aim of this study was to investigate the association between infarction subtypes, biomarkers and END, and to identify patients with risk of unfavorable functional outcome. Materials and Methods: This prospective study enrolled 101 patients with AIS. Neurological status was evaluated according to NIHSS at acute onset, on days 2, 3, and 90. END was defined as ≥2-point increase of NIHSS within 72 hours. Functional outcome was assessed using NIHSS and the modified Rankin Scale (mRS) at day 90. Results: END was observed in 20, 8%. Patients with large artery disease had higher risk of developing END compared with patients with cardioembolism or small vessel disease (p <0.01). Significant higher blood glucose level and leukocytes were observed in the END group. Patients with END had higher scores of mRS at day 90 (p <0.01). Levels of NSE, IL-6, hsCRP and NT-proBNP were higher in the patients with unfavorable compared with favorable functional outcome. Conclusion: Large artery disease, high blood glucose and leukocytes levels are associated with END. Elevated levels of blood markers NSE, IL-6, HsCRP and NT-proBNP indicate poor functional outcome at 90 days after AIS. These patients must be identified and be offered treatment immediately in order to improve the functional outcome after AIS.

OCT and VEP correlate to disability in secondary progressive multiple sclerosis.

BACKGROUND: The afferent visual pathway provides a unique opportunity to monitor clinical and subclinical optic neuritis and features of neuroaxonal degeneration in secondary progressive MS. OBJECTIVE: To investigate the usefulness of visual evoked potentials (VEP) and optical coherence tomography (OCT) in evaluating SPMS, and the association between these modalities and clinical course and lesion load on the magnetic resonance imaging (MRI) in patients with SPMS with or without a history of optic neuritis (ON). METHODS: SPMS patients (n = 27) underwent clinical assessment with Expanded Disability Status Scale (EDSS) grading, visual acuity, OCT, and VEP examination. MRI of the brain and spinal cord were evaluated. Ordinal scores of VEP and MRI findings were used in the statistical analyses. RESULTS: The ganglion cell and inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thickness correlated with VEP latency. VEP P100 score correlated with EDSS. Linear regression showed an association between GCIPL thickness and EDSS as well as VEP P100 latency and EDSS. The MRI analyses were negative. CONCLUSION: VEP latency and GCIPL thickness correlated with disability measured as EDSS in patients with SPMS and are useful in monitoring SPMS patients.

Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes.

BACKGROUND: Teriflunomide 14 mg (Aubagio®) is a once-daily, oral drug approved for the treatment of relapsing forms of multiple sclerosis (MS). While the efficacy and safety of teriflunomide have been thoroughly characterised across an extensive clinical program, we were interested in studying performance of the drug with respect to quality-of-life (QoL) outcomes in persons with MS in a real-world setting. METHODS: Teri-LIFE was a prospective, open label, non-interventional, observational, multi-centre study that enrolled 200 teriflunomide-treated patients from three Nordic countries. The primary outcome measure changes in patient-reported QoL over 24 months as measured by the Short Form-36 (SF-36) questionnaire. Secondary endpoints included clinical efficacy, fatigue, safety, treatment satisfaction (Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM-1.4)), treatment adherence, and health economic outcomes. Most assessments were made at baseline and then at 6-monthly intervals. RESULTS: Overall, changes in SF-36 scores from baseline to last visit indicated a stable QoL during treatment with teriflunomide for up to 24 months. Relapse activity decreased during the study compared to the pre-baseline period (p<0.001), patient-reported disability increased marginally, and no substantial change was seen in fatigue scores. The mean scores for TSQM domains increased nominally though not significantly from Month 6 to Month 24. The convenience and side effects TSQM domains recorded the highest median scores, indicating the acceptability of oral teriflunomide in this cohort. This was reflected in a generally high treatment adherence and decreased healthcare utilization during the study period. Some differences were seen between treatment-naïve and previously treated patients, likely reflecting different patient demographics and disease status at study entry, along with different treatment expectations. CONCLUSION: Teri-LIFE offers a reliable snapshot of QoL, efficacy, safety, and health economic outcomes in persons with relapsing MS treated with teriflunomide in routine clinical practice in Nordic countries The results were consistent with previous clinical trials and real-world studies.

Diagnosis and classification of optic neuritis.

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.

Optical Coherence Tomography Revealing Ganglion Cell Loss in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Although there may theoretically be a disturbance in the eye or the visual pathways due to abnormal cerebrospinal fluid (CSF) dynamics in idiopathic normal pressure hydrocephalus (iNPH), it has not been studied systemically. Optical coherence tomography (OCT) is a noninvasive, reproducible procedure for quantitative and qualitative analysis of retinal morphology. METHODS: OCT was used to study the eye fundus before and after a CSF tap test in patients with iNPH compared with healthy individuals (HIs). Twelve patients with iNPH (6 females and 6 males) with a median age of 76 years (64-84 years) and 21 HIs (11 females and 10 males) with a median age of 73 years (64-79 years) were included. The patients underwent neurological, cognitive, and physiotherapeutic evaluation. Brain magnetic resonance imaging, CSF tap test via lumbar puncture, and subsequently CSF analysis were performed. OCT was performed before and after CSF removal. HIs underwent OCT once. RESULTS: The patients had significantly reduced retinal ganglion cell layer thickness 71 µm (56-81 µm) compared with the HIs, 79.5 µm (72-90 µm) (P = 0.001), but no significant changes were observed before or after the CSF tap test. All patients improved in motor function in a 10-m walk test after the CSF tap test. The median CSF pressure was 15 and 1 cm H2O, respectively, before and after lumbar puncture with removal of median 43.5 mL CSF. CONCLUSIONS: This pilot study shows OCT findings that differ from HIs and implies a rational for becoming a valuable tool in the diagnosis of iNPH. Further studies are warranted to elucidate the pathology of the retina in iNPH.

Homonymous visual field defect and retinal thinning after occipital stroke.

INTRODUCTION: Stroke is the most common cause of homonymous visual field defects (VFD). About half of the stroke patients recover from VFD. However, relationship between VFD and retinal changes remains elusive. PURPOSE: To investigate the association between occurrence of VFD, changes of macular ganglion cell and inner plexiform layer (GCIPL) and its axon retinal nerve fiber layer (RNFL) detected with optical coherence tomography (OCT). PATIENTS AND METHODS: The study consists of retrospective review of medical records and follow-up examinations. Patients with acute occipital stroke were registered. VFD was identified with confrontation and/or perimetry tests at the onset. At follow-up, the patients were examined with visual field tests and OCT measurements. RESULTS: Thirty-six patients met the inclusion criteria. At onset, 26 patients (72%) had VFD. At follow-up >1 year after stroke, 13 patients (36%) had remaining VFD: 5 had homonymous hemianopia, 5 had homonymous quadrantanopia, and 3 had homonymous scotomas. Average thickness of GCIPL and RNFL were significantly reduced in each eye in patients with VFD compared to non-VFD (NVFD) (p < .01 for all comparisons). Thickness of superior and inferior RNFL quadrants was significantly reduced in VFD compared to NVFD (p < .01 for both). Among these 13 patients, 4 had characteristic homonymous quadrant-GCIPL thinning, 2 had characteristic homonymous hemi-GCIPL thinning, and 7 had diffuse GCIPL thinning. CONCLUSION: GCIPL and RNFL thinning were observed in the patients with VFD. GCIPL thinning appears in two forms: atypical diffuse thinning, or homonymous hemi-GCIPL thinning. Examining GCIPL and RNFL provides easy and reliable objective measures and is therefore proposed to be of predictive value on visual function.

OCT measurements of optic nerve head changes in idiopathic intracranial hypertension.

OBJECTIVE: Severity of papilledema and vision loss constitute a basis for therapeutic intervention in idiopathic intracranial hypertension (IIH), but both are often subjective and insensitive in guiding clinical management. The aim of this study was to identify reliable and sensitive measurements of optic nerve head (ONH) and macula, to provide objective guidance for prognostic evaluation and treatment in IIH. We analyzed potential of spectral domain optical coherence tomography (SD-OCT), to measure neuro-retinal rim thickness and area, optic cup-to-disc ratio (C/D) and cup volume of ONH which have not previously been reported in IIH. In parallel, thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell layer (GCL) together with inner plexiform layer (IPL) (GCL-IPL) were examined. RESULTS: All 7 enrolled IIH patients had increased neuro-retinal rim thickness (p<0.01 for both eyes) and rim area (p<0.05), decreased C/D (p<0.01) and optic cup volume (p<0.01) when compared to findings in 18 sex- and age-matched healthy controls (HC). In a longitudinal study, two IIH patients were followed repetitively by SD-OCT before and after measurement of intracranial pressure (ICP) and removal of cerebrospinal fluid (CSF) by lumbar puncture. Rim thickness and area, C/D and optic cup volume remained altered. RNFL thickness may change with very high ICP, but not immediately after CSF removal. GCL-IPL thickness was unchanged irrespective of ICP change or CSF removal. CONCLUSION: SD-OCT allows detection of ONH changes even in subtle IIH without papilledema and has potential for routine use in IIH.