Multimodal imaging in early onset non-neovascular pigment epithelial detachments.

PURPOSE: To describe multimodal imaging of two cases of bilateral non-vascularized pigment epithelial detachments (PED) in young patients with a long-term follow-up. METHODS: A complete ophthalmological examination was performed at each follow-up visit including best corrected visual acuity (BCVA), intraocular pressure, slit lamp examination, spectral domain optical coherence tomography (SD-OCT), fluorescein and indocyanine green angiography, OCT angiography. RESULTS: Multimodal imaging of two women presenting avascular PED, aged 43 and 57, respectively, was described. In both patients, SD-OCT revealed a high central macular hyporeflective elevation corresponding with PED. Both patients showed a choroidal layer thicker than 420 µm. Fluorescein and indocyanine green angiography didn't show any choroidal neovascularization either at early or late frames. Cross-sectional and en face optical coherence tomography angiography (OCTA) didn't show any flow beneath the PED. During the follow up period one eye showed a retinal pigment epithelium tear and all eyes showed the presence of apical sub-retinal fluid and hyperreflective material on the top of the PED. None of the two patients showed any sign of atrophy during the follow-up period. CONCLUSION: The peculiar characteristics of the presented cases suggest that specific pathogenetic mechanisms, not necessarily related to age related macular degeneration, may play a key role in the development of these lesions. Whether early onset of such drusenoid PED is a specific entity resulting from a genetic deficit of lipid transporters in the RPE is unknown. Further genetic and metabolic studies should be conducted.

Ocrelizumab versus fingolimod after natalizumab cessation in multiple sclerosis: an observational study.

BACKGROUND: Exit strategy after natalizumab cessation in multiple sclerosis (MS) is a crucial point because the risk of disease reactivation is high during this period. The objective of this observational study was to compare ocrelizumab to fingolimod after natalizumab cessation in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: All RRMS patients starting fingolimod or ocrelizumab within 6 weeks after natalizumab cessation were included. The primary endpoint was the annualized relapse rate (ARR) at 1 year. RESULTS: We included 54 patients receiving fingolimod and 48 patients receiving ocrelizumab after natalizumab cessation. In multivariate analysis, ARR at 1 year was significantly lower in the ocrelizumab group than in the fingolimod group (0.12 ± 0.39 versus 0.41 ± 0.71, p = 0.026), i.e. a 70.7% lower relapse rate. The cumulative probability of relapses at 1 year was 31.5% (17/54 patients) with fingolimod and 10.4% (5/48 patients) with ocrelizumab, corresponding to a hazard ratio of 3.4 (95% confidence interval: 1.1-11, p = 0.04). CONCLUSIONS: Our results suggest ocrelizumab is potentially a better exit strategy than fingolimod after natalizumab cessation.

Glial Fibrillary Acidic Protein Autoimmunity: A French Cohort Study.

BACKGROUND AND OBJECTIVES: To report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies. METHODS: We retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers. RESULTS: We identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies. DISCUSSION: GFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.

Recurrent seizures of autoimmune origin: emerging phenotypes.

OBJECTIVE: Recurrent seizures of autoimmune origin (AEp) are one of the most frequent causes of recurrent seizures or suspected epilepsy of unknown cause. The aim of this study was to identify specific phenotypes corresponding to AEp. METHODS: We retrospectively reviewed features of patients with recurrent seizures of unknown cause and investigated for suspected AEp (January 2015-May 2018). Patients were separated in: (1) AEpAb+: AEp with positive autoantibodies; (2) AEpAb-: suspected AEp (inflammatory central nervous system (CNS) profile) without autoantibodies; (3) NAEp: epilepsy without CNS inflammation. RESULTS: Eighty-nine epileptic patients underwent a CSF antibody detection. From the remaining 57 epileptic patients (32 excluded for a differential diagnosis), 61.4% were considered as AEp. 21% were AEpAb+ (4 NMDAR, 2 GABAbR, 3 GAD-Ab, 2 LGi1, 1 CASPR2), 40.4% AEpAb-, and 38.6% NAE. AE (AEpAb+ and AEpAb-) was significantly associated with antibody prevalence in epilepsy (APE) score ≥ 4 (80%), encephalitic phase (71.4%), psychiatric involvement (64.7%), cognitive impairment (50%), and status epilepticus (41.2%). Within the group of 29 patients without encephalitic phase and with chronic epilepsy (NEPp), 34.5% were defined as AEp. 10.4% were AEpAb+ (2 GAD, 1 CASPR2) and 24.1% were AEpAb-. NEP AEp was associated with non-cerebral autoimmune disorders, short epileptic disease duration, and cognitive impairment. CONCLUSIONS: Autoimmune cause (AEp) should be assessed in patient suffering from recurrent seizures of unknown cause. Acute encephalitis is clearly the main AEp phenotype. AEp was also defined in more than one-third of chronic epilepsy patients (NEP) of unknown cause. Then, AEp may be combined with other autoimmune comorbidities, a shorter evolution of recurrent seizures, and cognitive impairment.

Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis.

Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities. Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity. Design, Setting, and Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020. Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms. Main Outcomes and Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes. Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01). Conclusions and Relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.

GAD65-Ab encephalitis and subtle focal status epilepticus.

AIMS: To delineate common epilepsy features associated with the presence of glutamic acid decarboxylase autoantibodies (GAD65-Ab). METHODS: Three consecutive cases of GAD65-Ab encephalitis patients, followed in our neurological department, were investigated with regards to clinical semiology and EEG. RESULTS: These patients presented new-onset subtle ictal clinical features. Patients 1 and 2 described prolonged and transitory feelings of "déjà vu - déjà vécu" and a "dreamy state". Patient 3 was admitted for subsequent transient aphasia events followed by paroxysmal behavioural disturbances. Epileptic origin of the symptoms was confirmed using either a standard EEG (observation of temporal status epilepticus in one case) or a prolonged EEG (focal epileptiform activity during an asymptomatic period for two patients). All patients suffered from clinical focal status epilepticus. Patients 1 and 2 presented with temporo-mesial seizures in agreement with the definition for limbic encephalitis, whereas Patient 3 presented with neocortical (lateral temporal and frontal lobe) seizures arguing for a non-limbic encephalitis. A high level of GAD65-Ab was found in cerebral spinal fluid, confirming a diagnosis of epilepsy associated with GAD65-Ab encephalitis. CONCLUSION: Encephalitis seems to be a frequent neurological syndrome associated with GAD65-Ab disorders. Epilepsy may be more frequent and severe than currently suggested, as ictal semiology may be subtle for these outpatients in whom standard EEG is commonly falsely reassuring. Subtle focal status epilepticus is a particular semiology of the GAD65-Ab encephalitis spectrum.

Parafoveal OCT Angiography Features in Diabetic Patients without Clinical Diabetic Retinopathy: A Qualitative and Quantitative Analysis.

PURPOSE: To evaluate the capacity of OCT angiography (OCTA) for detecting infraclinical lesions in parafoveal capillaries in diabetic patients without diabetic retinopathy (DR). METHODS: This prospective observational cross-sectional case-control study analyzed the superficial and deep capillary plexuses (SCP and DCP) on macular OCTA scans (3 × 3 mm) centered on the fovea. We compared 22 diabetic patients (34 eyes included) without DR diagnosis on color fundus photographs, with 22 age- and gender-matched nondiabetic controls (40 eyes included). Qualitative analysis concerned morphological ischemic capillary alterations. Quantitative analysis measured foveal avascular zone (FAZ) size, parafoveal capillary density, and enlargement coefficient of FAZ between SCP and DCP. RESULTS: Neither the qualitative nor quantitative parameters were significantly different between both groups. No microaneurysms or venous tortuosity was observed in any of the analyzed images. On the SCP, the mean FAZ area was 0.322 ± 0.125 mm2 in diabetic patients and 0.285 ± 0.150 mm2 in controls, P = 0.31. On the DCP, the mean FAZ area was 0.444 ± 0.153 mm2 in cases and 0.398 ± 0.138 mm2 in controls, P = 0.20. CONCLUSION: OCTA did not detect infraclinical qualitative or quantitative differences in parafoveal capillaries of diabetic patients without DR in comparison with nondiabetic controls.

Lymphocytic Meningitis in Patients with Sympathetic Ophthalmia.

PURPOSE: This study aimed at reporting lymphocytic meningitis in patients diagnosed with sympathetic ophthalmia (SO). METHODS: In this single-center retrospective observational case series, we reviewed cases diagnosed with SO. We analyzed the patients' inciting injuries, the characteristics of uveitis and the cerebrospinal fluid (CSF) analyses. RESULTS: Nine patients were diagnosed with SO and CSF analyses were available in all cases. Four cases had lymphocytic pleocytosis, 3 of which showed marked CSF inflammation with more than 300 lymphocytes/mm3. The inciting event in these 3 patients was a globe perforation injury, whereas 4 patients without meningitis had SO following a surgical intervention. CONCLUSIONS: In this case series of patients with SO, lymphocytic meningitis was a common finding. The prevalence of meningitis in patients with SO and its value for the diagnosis of the disease needs to be further studied.

Normative Data for Vascular Density in Superficial and Deep Capillary Plexuses of Healthy Adults Assessed by Optical Coherence Tomography Angiography.

PURPOSE: To establish a normative database for vascular density (VD) and foveal avascular zone (FAZ) at the superficial (SCP) and deep capillary plexus (DCP) in healthy subjects with optical coherence tomography (OCT) angiography. METHODS: The study was a retrospective chart review of healthy patients who had undergone OCT angiography imaging. A 3- × 3-mm area, centered on the fovea, was scanned for all the study eyes. The automated segmentation allowed separate analysis of the SCP, the DCP, and a comprehensive C-scan including both vascular layers. On the obtained images, VD and FAZ measurements were computed. Interobserver reproducibility and intraobserver repeatability were also assessed. RESULTS: A total of 135 eyes of 70 subjects (51% male) were analyzed. The mean age was 48.3 ± 17.5. We divided patients into group 1, from 20 to 39 years of age; group 2, from 40 to 59 years; and group 3, age 60 years or older. At the level of the SCP, mean VD and mean FAZ ± SD were, respectively, 52.58 ± 3.22% and 0.28 ± 0.1 mm2. At the level of the DCP, mean VD and mean FAZ were 57.87 ± 2.82% and 0.37 ± 0.12 mm2, respectively. The mean VD was significantly higher (P < 0.05) in DCP compared with SCP in all Early Treatment Diabetic Retinopathy Study (ETDRS) sectors and in all age groups. Vascular density was higher in women than in men after 60 years (P < 0.01). After adjustment on the signal strength index (SSI), the mean VD remained directly correlated with the age range and sex. The mean FAZ area was lower in group 3 (P < 0.05). Interobserver reproducibility was 0.78 to 0.99 in SCP and 0.67 to 0.92 in DCP, and intraobserver repeatability was 0.64 to 0.93 in SCP and 0.63 to 0.87 in DCP. CONCLUSIONS: Our study has provided, for the first time, age-related VD mapping data using OCT angiography in healthy subjects. The prototype software used in this study may help to improve the concept of VD grading with high inter- and intraexaminer repeatability and interexaminer reproducibility.