Impact of Immune Checkpoint Inhibitors on the Course of Multiple Sclerosis.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) are increasingly used in cancer treatment. Their mechanism of action raises the question of possible exacerbation of preexisting multiple sclerosis (MS). The aim of our study was to assess the risk of increased MS activity, defined by the occurrence of a relapse and/or a new MRI lesion, after ICI initiation. METHODS: This French multicentric study collected retrospective and prospective data on patients with MS treated with ICIs after a cancer diagnosis. RESULTS: We identified 18 patients with a median age of 48 years. Three of them (17%), all aged 50 years or younger, with a relapsing-remitting course, showed clinical and/or radiologic signs of MS activity 3 to 6 months after ICI initiation. They had stopped disease-modifying treatment (DMT) several months earlier, at the time of cancer diagnosis. Only one had both clinical and MRI activity, with mild severity and complete recovery. DISCUSSION: Our study suggests that the overall risk of MS activity under ICI is low and could be mainly driven by DMT discontinuation, as in MS in general. Although larger studies are needed for better risk assessment in younger patients with more active disease, ICI should be considered when needed in patients with MS.

Long-standing prion dementia manifesting as posterior cortical atrophy.

Prion diseases commonly manifest with the phenotype of subacute myoclonic encephalopathy. However, genetic forms of prion disease may have prolonged evolution mimicking neurodegenerative disease. We present the clinical and neuropathological features of a family with an early and long-standing dementia manifesting with posterior cortical atrophy and related to a 120 bp insertional mutation of the prion protein gene. Two cases exhibited mixed prion and Aß pathology. The differential diagnosis with Alzheimer disease is discussed.

Challenges of switching towards anti-CD20 monoclonal antibodies in RR-MS: A monocentric study.

BACKGROUND: Anti-CD20 monoclonal antibodies (mAb) have demonstrated their drastic efficacy in the treatment of active relapsing-remitting multiple sclerosis (RR-MS). This study investigates the management of their initiation after another disease modifying therapy (DMT). The objective of this study was to assess the frequency and the risk factors of relapses during the wash-out period (WP) between cessation of last DMT and initiation of anti-CD20 mAb in RR-MS. METHODS: All non-naive RR-MS patients who initiated a treatment with Rituximab or Ocrelizumab between 2016 and 2019 have been included in this retrospective monocentric study. Univariate and multivariate analysis were conducted to evaluate risk factors of relapses during the WP. RESULTS: 73 patients (mean age 35.3 years, standard deviation (SD): 8.7 years) were included, with a mean number of 3.1 (SD: 1.3) previous DMTs. The DMT most frequently received before the switch was Fingolimod (Fg, 31 patients, 42.5%). 20 patients (27.4%) experienced relapses during the WP. Risk factors were previous treatment by Fg (p = 0.001) and WP duration (p = 0.032). Among patients switching from Fg, the probability of experiencing a relapse was 35% after 1 month of wash-out. CONCLUSION: This study suggests to shorten the WP duration when switching towards anti-CD20 mAb, especially after Fg, to avoid relapses.

Neuro-ophthalmological manifestations of Behçet's disease.

BACKGROUND: The neuro-ophthalmological manifestations of Behcet's disease (BD) are rare, and data regarding their characteristics and outcome are lacking. OBJECTIVE: To report prevalence, main characteristics and outcome of neuro-ophthalmological manifestations in BD. PATIENTS AND METHODS: This is a retrospective monocentric study of 217 patients diagnosed with neuro-Behçet's disease (NBD), of whom 29 (13.3%) patients presented with neuro-ophthalmological manifestations (55% of men and mean±SD age of 26±8 years). All patients underwent a detailed ophthalmological examination and were followed up in the internal medicine and the ophthalmology departments. RESULTS: Neuro-ophthalmological manifestations were the first presentation of BD in 45% of patients and developed later in the course of the disease in 55% of patients. They are divided into parenchymal (PM) and non-parenchymal (NPM)-related manifestations in, respectively, 13 patients (45%) and 16 patients (55%). PM included papillitis in seven patients (53.8%), retrobulbar optic neuritis in four patients (30.8%) and third cranial nerve palsy in two patients (15.4%). NPM included papilloedema related to cerebral venous thrombosis in all 16 patients, of whom 6 patients (37.5%) had sixth cranial nerve palsy. At initial examination, 93.1% of patients had visual alterations, including mainly decreased visual acuity visual field defects and/or diplopia. All patients were treated with corticosteroids and 79% of patients received immunosuppressive agents. After treatment, the visual outcome improved or stabilised in 66.7% of patients while it worsened in 33.3. The mean±SD logarithm of the minimum angle of resolution visual acuity improved from 0.4±0.3 at diagnosis to 0.2±0.3 after therapy. 10.3% and 3.4% of patients were legally blind at diagnosis and after therapy, respectively. CONCLUSION: Neuro-ophthalmological manifestations of BD represented 13% of NBD. They could be potentially severe and disabling. Prompt treatment is the key factor in improving visual outcome.

Plasma exchange response in 34 patients with severe optic neuritis.

Optic neuritis could lead to severe visual impairment despite corticosteroids. Our aim was to evaluate the rate of visual improvement in patients treated with plasma exchange (PLEX) for severe steroid unresponsive optic neuritis and to identify predictive factors of outcome. Thirty-four patients (41 optic nerves damaged) with remaining visual acuity of 0.1 or less despite steroid pulse therapy were treated with PLEX from September 2010 to May 2015. Demographic and clinical neuro-ophthalmic findings, and spectral domain-optical coherence tomography data before PLEX treatment were analyzed. The mean symptom duration before PLEX was 34.6 days (median 28 days; range 6-92 days). After PLEX, the median final visual acuity was 0.8 and in 56 % of cases, final acuity was 0.5 or better. Past history of ipsilateral optic neuritis was associated significantly with poor outcome defined as final acuity less than 0.5. No significant difference in the visual outcome after PLEX was found between multiple sclerosis and neuromyelitis optica. In conclusion, this observational study showed that PLEX as second-line therapy led to a functionally important visual recovery in more than half patients with severe optic neuritis.

Efficacy of Anti-TNFα in Severe and Refractory Neuro-Behcet Disease: An Observational Study.

To report the safety and efficacy of anti-tumor necrosis factor α (TNFα) therapy in severe and refractory neuro-Behçet disease (NBD) patients.Observational, multicenter study including 17 BD patients (70.6% of male, with a median age of 39.3 [24-60] years), with symptomatic parenchymal NBD, refractory to previous immunosuppressant and treated with anti-TNFα (infliximab 5 mg/kg [n = 13] or adalimumab [n = 4]). Complete remission was defined by the disappearance of all neurological symptoms and by the improvement of radiological abnormalities at 12 months.Overall improvement following anti-TNF was evidenced in 16/17 (94.1%) patients including 6 (35.3%) complete response and 10 (58.8%) partial response. The median time to achieve remission was 3 months (1-6). The median Rankin score was 2 (1-4) at the initiation of anti-TNFα versus 1 (0-4) at the time of remission (P = 0.01). Corticosteroids have been stopped in 4 (23.5%) patients, and reduced by more than 50% as compared with the dosage at baseline in 10 (58.8%) patients. Side effects occurred in 23.5% of patients and required treatment discontinuation in 17% of cases.TNF blockade represents an effective therapeutic approach for patients with severe and refractory NBD, a difficult to treat population.

Long-term outcome of neuro-Behçet's disease.

OBJECTIVE: To report the long-term outcome of neurologic involvement in patients with Behçet's disease (BD). METHODS: We performed a retrospective analysis of 115 patients who fulfilled the international criteria for BD (57% male; median age 37 years [interquartile range (IQR) 30-46 years]) and had neuro-BD (NBD) after exclusion of cerebral venous thrombosis. Factors associated with relapse of NBD, inability to perform activities of daily living, and mortality were assessed. RESULTS: Seventy-eight patients (68%) presented with acute NBD and 37 (32%) presented with a progressive course. The HLA-B51 allele was carried by 49% of the patients. Overall, 46 of 115 patients (40%) had severe disability at baseline, represented by a Rankin score of ≥3. The 5- and 7-year event-free survival rates were 65% and 53%, respectively. In multivariate analysis, a positive HLA-B51 status was independently associated with the risk of NBD relapse, with an odds ratio (OR) of 3.6 (95% confidence interval [95% CI] 1.5-9.1). After a median followup of 73 months (IQR 59-102 months), 29 patients (25.2%) became dependent (were unable to perform activities of daily living) or died. Factors independently associated with poor outcome were paresis at onset (OR 6.47 [95% CI 1.73-24.23]) and location of inflammatory lesions at the brainstem on magnetic resonance imaging (OR 8.41 [1.03-68.43]). All 115 patients were treated with corticosteroids; 53 (46.1%) also took cyclophosphamide and 40 (34.8%) also took azathioprine. A trend toward longer event-free survival was observed in patients with severe NBD (i.e., with a Rankin score of ≥3 at onset) receiving intravenous cyclophosphamide compared with those receiving azathioprine (P = 0.06). CONCLUSION: Our findings indicate that NBD is a severe condition in which patients with the HLA-B51 allele appear to experience a worse prognosis.

High prevalence of IgG4-related lymphoplasmacytic infiltrative disorder in 25 patients with orbital inflammation: a retrospective case series.

AIMS: To evaluate retrospectively the prevalence of positive IgG4-immunostaining in orbital tissue of patients with idiopathic orbital inflammation and to compare the clinical, radiographic and pathologic features among patients with and without IgG4-positive cells. PATIENTS AND METHODS: 25 patients with biopsy-proven idiopathic orbital inflammation examined from January 2006 through December 2011 were included. Immunohistochemistry with IgG and IgG4 immunostaining from biopsy specimens of all patients was performed. Tissue with more than 10 IgG4-positive plasma cells per high-power field and with a ratio of IgG4+/IgG+ plasma cells of more than 40% was scored as positive. Histopathologic features, demographic and clinical data, radiologic findings, treatment and follow-up information for each patient were analysed. RESULTS: Immunohistochemical staining showed 10 cases (40%) were IgG4 positive. The symptoms and signs included eyelid or periocular swelling/mass in all, pain (3/10), extraocular muscle restriction (3/10), proptosis (5/10) and/or decreased vision (4/10). Demographic and clinical findings of these patients did not differ from those with IgG4-negative cells. The presence of positive IgG4-immunostaining in orbital tissue was significantly associated with characteristic pathological features (more background fibrosis, lymphoid hyperplasia, plasma cells and phlebitis). CONCLUSIONS: Finally, 40% of patients with biopsy-proven orbital inflammation were classified as IgG4-RD, with typical histological features, but without specific clinical or radiological findings.