Prospective longitudinal study on prognostic factors of visual recovery and structural change after a first episode of optic neuritis.

BACKGROUND AND PURPOSE: This study was undertaken to determine the role of optical coherence tomography (OCT) in predicting the final visual and structural outcome, and to evaluate the correlation between functional eye outcome and retinal changes, in patients with a first episode of optic neuritis (ON). METHODS: In this prospective study, consecutive adult patients with acute ON underwent ophthalmological evaluation at baseline and at 1 and 12 months, including OCT measurements of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell and inner plexiform layer, and inner nuclear layer thicknesses; high- and low-contrast visual acuity; visual field assessment; and baseline brain magnetic resonance imaging. Univariate and multivariate linear regressions were used to assess predictive factors of outcome. Correlations between 12-month visual function and retinal structure were estimated by Spearman coefficients. Two groups of patients were analyzed, with or without multiple sclerosis (MS). RESULTS: Among 116 patients, 79 (68.1%) had MS, and 37 (31.9%) had ON not related to MS (including 19 idiopathic [i.e., isolated] ON, and 13 and five with myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies, respectively). We found no independent predictive factor of visual and retinal outcome. Analysis of the relationship between the visual field test (mean deviation) and pRNFL thickness demonstrated a threshold of 75.4 µm and 66.4 µm, below which the mean deviation was worse, for patients with MS (p = 0.007) and without MS (p < 0.001), respectively. CONCLUSIONS: We found that inner retinal layer measurements during the first month are not predictive of final outcome. The critical threshold of axonal integrity, below which visual function is damaged, is different between patients with and without MS.

A Clinico-Radiological Study of Cerebral Amyloid Angiopathy-Related Inflammation.

OBJECTIVE: To describe the clinico-radiological features and long-term prognosis in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri). METHODS: Twenty-eight CAA-ri patients were recruited retrospectively from 6 neurological centers. We recorded the clinico-radiological and biological data, at baseline and during follow-up. Baseline characteristics associated with relapse risk and prognosis were assessed. RESULTS: Five patients had pathologically confirmed CAA-ri whereas 23 had probable (n = 21) or possible (n = 2) CAA-ri. The mean age was 72 years; main clinical symptoms included confusion (54%), hemiparesis (36%), and aphasia (29%). Cerebral MRI disclosed a brain parenchymal lesion (89%), which was usually multifocal (82%) and bilateral (89%). It was associated with gadolinium enhancement (84%), small ischemic lesions (39%), cortical superficial siderosis (CSS; 50%), and a high number of microbleeds (mean 240 ± 277). An isolated leptomeningeal involvement was observed in 3 patients with pathological confirmation. Despite a favorable initial evolution after treatment, we observed a 42% risk of relapse, mostly within the first year (83%). After a mean follow-up of 2 years, 29% died and 25% had a marked disability. Disseminated CSS was associated with death. CONCLUSION: Despite an apparently favorable initial evolution, CAA-ri is characterized by a poor prognosis. Diagnostic criteria should consider patients with isolated leptomeningeal involvement.

Cerebral Amyloid Angiopathy-Related Inflammation and Biopsy-Positive Primary Angiitis of the CNS: A Comparative Study.

BACKGROUND AND OBJECTIVES: Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS. METHODS: Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk. RESULTS: This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, p < 0.001), acute subarachnoid hemorrhage (15% vs 2%, p = 0.02), cortical superficial siderosis (27% vs 4%, p < 0.001), ≥1 lobar microbleed (94% vs 26%, p < 0.001), past intracerebral hemorrhage (17% vs 4%, p = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, p < 0.01), and leptomeningeal enhancement (70% vs 27%, p < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, p < 0.01), motor deficits (56% vs 36%, p = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, p < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS (p = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, p = 0.04). CONCLUSION: Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.

Hemophagocytic Lymphohistiocytosis Gene Mutations in Adult Patients Presenting With CLIPPERS-Like Syndrome.

OBJECTIVE: To determine whether adult cases of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) may be related to familial hemophagocytic lymphohistiocytosis (HLH) causes, we have screened patients with adult-onset CLIPPERS for mutations in primary HLH-associated genes. METHODS: In our cohort of 36 patients fulfilling the criteria for probable or definite CLIPPERS according to the CLIPPERS-2017 criteria, we conducted a first study on 12 patients who consented to genetic testing. In these 12 patients, systemic HLH criteria were searched, and genetic analysis of 8 genes involved in primary HLH was performed. RESULTS: Four definite and 8 probable CLIPPERS were enrolled (n = 12). Mutations involved in HLH were identified in 2 definite and 2 probable CLIPPERS (4/12). Three of them had biallelic PRF1 mutations with reduced perforin expression in natural killer cells. The remaining patient had biallelic UNC13D mutations with cytotoxic lymphocyte impaired degranulation. None of the mutated patients reached the criteria for systemic HLH. During follow-up, 3 of them displayed atypical findings for CLIPPERS, including emergence of systemic non-Hodgkin lymphoma (1/3) and confluent gadolinium-enhancing lesions on brain MRI (3/3). CONCLUSIONS: In our patients presenting with adult-onset CLIPPERS, one-third have HLH gene mutations. This genetic treatable condition should be searched in patients with CLIPPERS, especially in those presenting with atypical findings.