Validation of the Behçet's Syndrome Overall Damage Index (BODI) for Retrospective Studies and a Proposal for Modification.

OBJECTIVE: Assessment of damage accrual over time is important for evaluating and comparing long-term results of treatment modalities and strategies. Retrospective studies may be useful for assessing long-term damage, especially in rare diseases. We aimed to validate Behçet's Syndrome Overall Damage Index (BODI) for use in retrospective studies by evaluating its construct validity, reliability, and feasibility in retrospectively collected data. Additionally, we aimed to determine missing items by evaluating Behçet's syndrome patients with different types of organ involvement and long-term follow-up. METHODS: We included 300 patients who had at least 2 clinic visits at 1-year intervals. The construct validity for use in retrospective trials was assessed by comparing BODI scores calculated from patient charts and during face-to-face visits. BODI was additionally scored using retrospective chart data by 2 different observers and by the same observer six months apart, in a blinded manner. The time for filling BODI was evaluated to assess feasibility. Additionally, damaged items that were missing from BODI were identified. RESULTS: There was a good correlation between the retrospective and face-to-face evaluation of BODI (ICC 0.99; %95 CI 0.99-0.99). Inter-observer and intra-observer agreement were good (ICC 0.96 and 1, respectively). The main damage items that BODI did not capture were hypertension, liver failure, lung parenchymal involvement, glaucoma, and lymphedema. CONCLUSION: BODI seems to be a reliable and feasible instrument for assessing damage in retrospective studies. Modifying BODI using the additional damage items identified in this study may make it an even better scale.

Erdheim-Chester disease of brain parenchyma without any systemic involvement: A case report and review of literature.

Erdheim-Chester disease is a non-Langerhans cell histiocytosis syndrome characterised by histiocytic infiltration of different organs and systems in the body. Erdheim-Chester disease with isolated central nervous system (CNS) involvement causes diagnostic difficulties due to the absence of systemic findings and may result in misdiagnosis and inaccurate treatment choices. The case discussed in this report exemplifies how challenging it is to diagnose Erdheim-Chester disease with isolated CNS involvement. This case, which presented with progressive pyramidocerebellar syndrome, was clinically and radiologically resistant to all immunosuppressive and immunomodulatory treatments administered. The presence of false negative results in repeated histopathological investigations and the absence of evidence for systemic disease hindered the diagnosis and treatment work-up. In this study, we reviewed and discussed the prominent features of the presented case in light of the relevant literature.

Infliximab for vascular involvement in Behçet's syndrome.

OBJECTIVE: Vascular involvement is an important cause of morbidity and mortality in patients with Behçet's syndrome (BS). We aimed to survey the efficacy and safety of infliximab (IFX) in BS patients with vascular involvement followed in a dedicated tertiary center. METHODS: Charts of all BS patients who used IFX for vascular involvement between 2004 and 2022 were reviewed. Primary endpoint was remission at Month 6, defined as lack of new clinical symptoms and findings associated with vascular lesion, lack of worsening of the primary vascular lesion and a new vascular lesion on imaging, and CRP < 10 mg/L. Relapse was defined as development of a new vascular lesion or recurrence of the preexisting vascular lesion. RESULTS: Among the 127 patients (102 men, mean age at IFX initiation: 35.8 ± 9.0 years) treated with IFX, 110 (87%) had received IFX for remission induction and 87 of these (79%) were already on immunosuppressives when the vascular lesion requiring IFX developed. The remission rate was 73% (93/127) at Month 6 and 63% (80/127) at Month 12. Seventeen patients experienced relapses. Remission rates were better among patients with pulmonary artery involvement and venous thrombosis compared to patients with non-pulmonary artery involvement and venous ulcers. Fourteen patients had adverse events leading to IFX discontinuation and 4 had died due to lung adenocarcinoma, sepsis, and pulmonary hypertension-related right heart failure due to pulmonary artery thrombosis (n = 2). CONCLUSION: Infliximab seems to be effective in majority of BS patients with vascular involvement, even in those who are refractory to immunosuppressives and glucocorticoids.

A Case of Coexistent Spinocerebellar Ataxia Type 2 and Primary Progressive Multiple Sclerosis-Coincidental or Associated?

Spinocerebellar ataxia type 2 (SCA2) is a dominantly inherited ataxia primarily characterised by progressive cerebellar syndrome, which is developed due to the expansion of the CAG trinucleotide repeat within the first exon of the ATXN2 gene. We report a rare case of a 41-year-old woman with coexistent genetically verified SCA2 and primary progressive multiple sclerosis (MS). Considering our case and a few others reported in the literature, as well as a possible genetic association between ATXN2 and MS susceptibility, we suggest that the coexistence of SCA and MS may not be coincidental, especially in patients with a progressive MS course.

Comparison of multiple sclerosis patients with or without rebound activity after fingolimod cessation: Five-year clinical outcomes.

BACKGROUND: Patients with multiple sclerosis (MS) who discontinue fingolimod might present with rebound activity. The reasons for the development of rebound have been identified, but there are limited data on the long-term clinical outcomes of these patients. This study aimed to compare the long-term outcomes of patients with MS with and without rebound activity after fingolimod discontinuation. METHODS: A total of 31 patients who discontinued fingolimod for various reasons with a minimum follow-up of 5 years were included in the study. Of these, 10 were assigned to the rebound group and 21 to the non-rebound group. Clinical and demographic data and 5-year clinical outcomes of both groups were prospectively examined. RESULTS: At fingolimod initiation, there were no significant differences in age, disease duration, and Expanded Disability Status Scale (EDSS) score. The annualized relapse rate (ARR) was significantly higher in the rebound group than in the non-rebound group before the fingolimod treatment (p = 0.005). In the rebound group, EDSS scores 2 months after rebound treatment and at the 5-year follow-up were not significantly different than before fingolimod initiation (p = 0.14 and p = 0.46, respectively). The last recorded EDSS was significantly higher in the non-rebound group than in the rebound group (3.6 ± 2.3 vs. 2.15 ± 1.4, p = 0.045). At the last follow-up, one patient was diagnosed with secondary progressive multiple sclerosis in the rebound group (10%), and 11 patients were in the non-rebound group (52.4%, p = 0.05). CONCLUSION: When rebound activity is well-monitored and treated after fingolimod discontinuation, no overall EDSS change is expected in the long-term follow-up.

Retrospective analysis of effectiveness of fingolimod in real life setting in Turkey (REFINE).

BACKGROUND: During multiple sclerosis (MS) treatment different modes of action such as lateral (interferon beta to glatiramer acetate or glatiramer acetate to interferon beta) or vertical (interferon beta/glatiramer acetate to fingolimod) drug switch can be performed. This study aims to investigate the clinical effectiveness of switching from the first-line injectable disease modifying treatments (iDMTs) to fingolimod (FNG) compared to switching between first-line iDMTs. METHODS: This is a multicenter, observational and retrospective study of patients with relapsing-remitting MS who had lateral and vertical switch. The observation period included three key assessment time points (before the switch, at switch, and after the switch). Data were collected from the MS patients' database by neurologists between January 2018 and June 2019. The longest follow-up period of the patients was determined as 24 months after the switch. RESULTS: In 462 MS patients that were included in the study, both treatments significantly decreased the number of relapses during the postswitch 12 months versus preswitch one year while patients in the FNG group experienced significantly fewer relapses compared to iDMT cohort in the postswitch 12 months period. FNG cohort experienced fewer relapses than in the iDMT cohort within the postswitch 2 year. The mean time to first relapse after the switch was significantly longer in the FNG group. DISCUSSION: The present study revealed superior effectiveness of vertical switch over lateral switch regarding the improvement in relapse outcomes. Patients in the FNG cohort experienced sustainably fewer relapses during the follow-up period after the switch compared the iDMT cohort. Importantly, switching to FNG was more effective in delaying time to first relapse when compared with iDMTs.

Emergence of new manifestations during infliximab treatment in Behçet's syndrome.

OBJECTIVES: Infliximab (IFX) is increasingly being used for the treatment of severe manifestations of Behçet's syndrome (BS). However, emergence of new manifestations has also been occasionally reported during IFX treatment. We aimed to assess the frequency of new manifestations in our BS patients treated with IFX. METHODS: A chart review was conducted to identify all BS patients treated with IFX in our clinic between 2004 and 2020. Demographic data, indications for IFX initiation, concomitant treatments and outcomes were recorded. A new manifestation was defined as the emergence of a new organ involvement or mucocutaneous manifestation developing for the first time during IFX treatment or within 12 weeks after the last infusion of IFX. RESULTS: Among our 282 patients who used IFX, 19 (7%) patients had developed a total of 23 new manifestations during a mean follow-up of 20.0 (15.3) months. Patients with vascular involvement were more likely to develop a new manifestation (12/19, 63%). Initial manifestations that required IFX were in remission at the time of new manifestation in 14/19 patients. IFX treatment was intensified (n = 6) and/or glucocorticoids, immunosuppressives or colchicine was added to IFX (n = 21). IFX was switched to another agent for the remaining manifestations (n = 8). These treatment modifications led to remission in 17/19 patients. CONCLUSION: New manifestations developed during IFX treatment in 7% of our patients with BS. They could be managed by intensifying IFX treatment or adding other agents in the majority of these manifestations.

Treatment of COVID-19-induced refractory status epilepticus by tocilizumab.

BACKGROUND AND PURPOSE: COVID-19 is a novel infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in which neurological complications have been increasingly recognized. Acute symptomatic epileptic seizures and status epilepticus are frequently reported neurological complications associated with this infection. The nervous system damage caused by SARS-CoV-2 may be mediated by the immune system. Interleukin 6 (IL-6), an important component of the cytokine storm, is directly correlated with the severity of symptoms. Tocilizumab is an inhibitor of IL-6 receptors, which blocks IL-6-mediated signal transduction and is used in the treatment of COVID-19 and status epilepticus. CASE REPORT: A patient with the Unverricht-Lundborg disease is presented who had developed refractory recurrent status epilepticus during COVID-19 infection, which was finally controlled by treatment with tocilizumab. DISCUSSION: Tocilizumab, an IL-6 inhibitor, may be considered as a treatment option in patients with status epilepticus and refractory seizures.

Treatment of multiple sclerosis-related trigeminal neuralgia with onabotulinumtoxinA.

BACKGROUND: The effectiveness of onabotulinumtoxinA (BTX-A) has been established in primary trigeminal neuralgia (TN). However, to the best of our knowledge, the efficacy of BTX-A in secondary TN has not yet been studied. OBJECTIVE: This study aimed to investigate the efficacy of BTX-A treatment in patients with multiple sclerosis-related trigeminal neuralgia (TN-MS) and compare the efficacy of BTX-A treatment between patients with primary trigeminal neuralgia (TN-P) and patients with TN-MS. METHODS: This was a retrospective medical record-review study. Demographic and clinical features and severity and frequency of pain before and 2 weeks after the BTX-A administration were extracted from the patient files. BTX-A was injected into the painful area subcutaneously and/or submucosally. BTX-A injections were performed by the same physician using the same methods. A reduction in severity and/or frequency of pain ≥50% was considered therapeutic efficacy. RESULTS: Fifty-three patients were included in this study. We classified 22 (42%) as TN-P and 31 (58%) as TN-MS. Treatment with BTX-A was effective in 16 of 31 (52%) patients with TN-MS and 10 of 22 (45%) with TN-P. BTX-A treatment was less effective in patients with a history of interventional treatments and more effective in patients with concomitant continuous pain (p = 0.007; odds ratio [OR]: 0.020-0.53 and p = 0.047; OR: 0.046-0.98, respectively). CONCLUSION: The BTX-A treatment was found to be effective in at least half of our cohort with TN-MS. Concomitant continuous pain and history of interventional treatments to the trigeminal nerve or ganglion might be predictive factors for the efficacy of BTX-A treatment.

Trigeminal neuropathy as presenting symptom of craniofacial venous metameric syndrome.

AIMS: Trigeminal neuropathy is more likely to suggest neuronal damage and occur due to secondary pathology than trigeminal neuralgia. Evaluation of underlying etiologies are necessary. CASE: A 29-year-old female patient presented with left sided continuous burning pain likened to pins and needles at maxillary distribution for about a year. Her examination was normal except left-sided buccal swelling without any skin or mucosal change. Cranial MRI revealed asymmetrical dilation of left Meckel's cave, bilateral cerebral developmental venous anomaly and left sided slow flow venous malformation from superior temporal fossa to masseter muscle. Cerebral angiography confirmed widespread venous return anomaly in both cerebral hemispheres and slow-flow venous malformation that does not fill in the early arterial phase in the left buccal space and superficial temporal fossa. Cerebrofacial venous metameric syndrome is diagnosed. Percutaneous sclerotherapy with alcohol is planned in three separate sessions, the first of the three planned sessions is performed yet and the patient stated that her neuropathic pain decreased by 40% afterwards. SIGNIFICANCE: Clinical manifestation of the cerebrofacial venous metameric syndrome depends on the localization of the lesions; therefore, venous anomalies in relation with the trigeminal branches can present with painful trigeminal neuropathy.

Higher antibody responses after mRNA-based vaccine compared to inactivated vaccine against SARS-CoV-2 in Behcet's syndrome.

There are limited data about humoral response to vaccine in Behçet's syndrome (BS). We compared SARS-CoV-2 antibody response after two doses of inactivated (Sinovac/CoronaVac) or mRNA (Pfizer/BioNTech) vaccines in patients with BS and healthy controls (HCs). We studied 166 (92M/74F) patients with BS (mean age: 42.9 ± 9.6 years) and 165 (75M/90F) healthy controls (mean age: 42.4 ± 10.4 years), in a single-center cross-sectional design between April 2021 and October 2021. A total of 80 patients with BS and 89 HCs received two doses of CoronaVac, while 86 patients with BS and 76 HCs were vaccinated with BioNTech. All study subjects had a negative history for COVID-19. Serum samples were collected at least 21 days after the second dose of the vaccine. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. We found that the great majority in both patient and HC groups had detectable antibodies after either CoronaVac (96.3% vs 100%) or BioNTech (98.8% vs 100%). Among those vaccinated with CoronaVac, BS patients had significantly lower median (IQR) titers compared to HCs [36.5 (12.5-128.5) vs 102 (59-180), p < 0.001]. On the other hand, antibody titers did not differ among patients with BS and HCs who were vaccinated with BioNTech [1648.5 (527.0-3693.8) vs 1516.0 (836.3-2599.5), p = 0.512). Among different treatment regimen subgroups in both vaccine groups, those who were using anti-TNF-based treatment had the lowest antibody titers. However, the difference was statistically significant only among those vaccinated with CoronaVac. Among patients vaccinated with BioNTech, there was no statistically significant difference between different treatment regimen groups. Compared to inactivated COVID-19 vaccine, mRNA-based vaccine elicited higher antibody titers among BS patients. Only in the CoronaVac group, patients especially those using anti-TNF agents were found to have low titers compared to healthy subjects. BS patients vaccinated with BioNTech were found to have similar seroconversion rates and antibody levels compared to healthy controls. Further studies should assess whether the low antibody titers are associated with diminished protection against COVID-19 in both vaccine groups.

Safety of SARS-CoV-2 vaccination in patients with Behcet's syndrome and familial Mediterranean fever: a cross-sectional comparative study on the effects of M-RNA based and inactivated vaccine.

Most of the published data relate to classical forms of rheumatic diseases (RD) and information on rare inflammatory disorders such as Behçet's syndrome (BS) and familial Mediterranean fever (FMF) is limited. We studied the frequency of side effects and disease flares after COVID-19 vaccination with either Pfizer/BioNTech or Sinovac/CoronaVac in 256 patients with BS, 247 with FMF, and 601 with RD. Telephone interviews were conducted using a questionnaire survey in a cross-sectional design in patients with BS, FMF, and RD followed by a single university hospital. Study participants were vaccinated either with CoronaVac (BS:109, FMF: 90, and RD: 343,) or BioNTech (BS: 147, FMF: 157 and RD: 258). The majority have received double dose (BS: 94.9%, FMF 92.3% and RD: 86.2%). BioNTech ensured a significantly better efficacy than CoronaVac against COVID-19 in all patient groups (BS: 1.4% vs 10.1%; FMF: 3.2% vs 12.2%, RD:2.7% vs 6.4%). Those with at least one adverse event (AE) were significantly more frequent among those vaccinated with BioNTech than those with CoronaVac (BS: 86.4% vs 45%; FMF: 83.4% vs 53.3%; and RD: 83.3% vs 45.5%). The majority of AEs were mild to moderate and transient and this was true for either vaccine. There were also AEs that required medical attention in all study groups following CoronaVac (BS: 5.5%, FMF: 3.3%, and RD:2.9%) or BioNTech (BS: 5.4%, FMF: 1.9%, and RD: 4.7%). The main causes for medical assistance were disease flare and cardiovascular events. Patients with BS (16.0%) and FMF (17.4%) were found to flare significantly more frequently when compared to those with RD (6.0%) (p < 0.001). This was true for either vaccine. BS patients reported mainly skin-mucosa lesions; there were however, 11 (4.3%) who developed major organ attack such as uveitis, thrombosis or stroke. Flare in FMF patients were associated mainly with acute serositis with or without fever. Arthralgia/arthritis or inflammatory back pain were observed mainly in the RD group. Our study demonstrates that BS and FMF patients vaccinated with either CoronaVac or BioNTech demonstrated similar AE profile and frequency compared to RD patients. AEs that required physician consultation or hospitalization occurred in all study groups after either CoronaVac or BioNTech. Increased frequency of flares in BS and FMF compared to that seen in RD might reflect defects in innate immunity and deserves further investigation. Caution should be required when monitoring these patients after vaccination.

The diagnostic contribution of intracranial vessel wall imaging in the differentiation of primary angiitis of the central nervous system from other intracranial vasculopathies.

PURPOSE: The aim of this study is to demonstrate the diagnostic effect of VWI in differentiating PACNS from other vasculopathies and its role in post-treatment follow-up in PACNS patients in this study. METHODS: In this prospective study, we included patients with clinical suspicion of PACNS who presented with new-onset ischemic events and had significant intracranial large vessel stenosis on DSA or MRA. VWI was performed on all patients. The imaging findings and final diagnoses were recorded. Control VWI was performed on patients with PACNS diagnosis after at least 3 months of treatment, and the change in findings was also evaluated. RESULTS: Twenty-three patients were included in the study had a median age of 40 (range 12-58). The most common clinical manifestations were focal neurologic deficits. According to the initial clinical evaluation, 10 patients (43.5%) were classified as PACNS and 13 patients (56.5%) as indeterminate for PACNS. After incorporating the VWI findings, the diagnosis of PACNS was confirmed in all clinically diagnosed PACNS patients. Concentric wall thickening and contrast enhancement were statistically significant in the PACNS group (p <0.001). According to concentric thickening and VWE features, sensitivity and specificity in distinguishing PACNS and other vasculopathies were 95.2%, 75% and 95.2%, 68.8%, respectively. Vessel wall enhancement regressed in 7 of 9 patients during a median follow-up period of 8 months (range 5.5-11.5) in PACNS patients who followed up. CONCLUSION: VWI seems a new and useful imaging method in the differential diagnosis of PACNS and might be a useful adjunct for post-treatment follow-up.

The efficacy of rituximab in patients with neuromyelitis optica spectrum disorder: A real-world study from Turkey.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are a group of antibody-mediated chronic inflammatory diseases of the central nervous system. Rituximab is a monoclonal antibody that leads to a reduction in disease activity. OBJECTIVE: To evaluate the efficacy of rituximab as monotherapy in NMOSD and to determine whether the efficacy varies depending on the presence of antibodies in this cohort. METHOD: This multicentre national retrospective study included patients with NMOSD treated with rituximab at least for 12 months from Turkey. The primary outcomes were the change in the annualised relapse rate, the Expanded Disability Status Scale (EDSS), the number of relapse and radiological activity-free patients. RESULTS: A total of 85 patients with NMOSD were included in the study. Of 85 patients, 58 (68.2%) were seropositive for anti-Aquaporin4-IgG (antI-AQP4-IgG). All patients were Anti-Myelin Oligodendrocyte Glycoprotein IgG (anti-MOG-IgG) negative. The median follow-up for rituximab treatment was 21 months (Q1 16-Q3 34.5). During rituximab treatment, the mean annualised relapse rate (ARR) significantly decreased from 1.45 ± 1.53 to 0.15 ± 0.34 (P < .001). In subgroup analyses, the mean ARR decreased from 1.61 ± 1.65 to 0.20 ± 0.39 in the seropositive group and 1.10 ± 1.19 to 0.05 ± 0.13 in the seronegative group. The mean EDSS improved from 3.98 ± 2.04 (prior to treatment onset) to 2.71 ± 1.59 (at follow-up) (P < .001). In the seropositive group, mean EDSS decreased from 3.94 ± 1.98 to 2.67 ± 1.54, and in the seronegative group, mean EDSS decreased from 4.07 ± 2.21 to 2.79 ± 1.73. There was no significant difference between anti-AQP4-IgG (+) and (-) groups in terms of ARR and EDSS. Sixty-four patients (75.2%) were relapse-free after the initiation of treatment. Seventy patients (82.3%) were radiological activity-free in the optic nerve, area postrema and brainstem. Additionally, 78 patients (91.7%) showed no spinal cord involvement after the treatment. CONCLUSION: Rituximab therapy is efficacious in the treatment of Turkish NMOSD patients independent of the presence of the anti-AQP4-IgG antibody.

Nervous system involvement in Behçet's syndrome.

PURPOSE OF REVIEW: Neurological involvement in Behçet's syndrome is defined as 'the occurrence of neurological symptoms and signs in a patient who meets the International Diagnostic Criteria for BS not otherwise explained by any other known systemic or neurological disease or treatment, and in whom objective abnormalities consistent with neuro-Behçet's syndrome (NBS) are detected either on neurological examination, neuroimaging studies (magnetic resonance imaging [MRI]), and/or on cerebrospinal fluid (CSF) examination'. Given that the neurological involvement of Behçet's syndrome carries a poor prognosis, we aimed to describe the differential diagnosis of NBS and highlight the different radiological patterns together with the treatment options. RECENT FINDINGS: Two distinct MRI patterns of spinal cord involvement in Behçet's syndrome according to T2-weighted axial images were described: 'Bagel Sign' pattern: a central lesion with hypointense core and hyperintense rim with or without contrast enhancement; and 'Motor Neuron' pattern: a symmetric involvement of the anterior horn cells. Infliximab prevents patients from having further attacks and even led to improvement in the neurological examination. SUMMARY: As the treatment options completely differ, a NBS diagnosis should be carefully made in patients with clinical and MRI features mimicking other central nervous system inflammatory disorders.

Cerebrospinal fluid chitinase-3-like protein 1 level is not an independent predictive factor for the risk of clinical conversion in radiologically isolated syndrome.

BACKGROUND: Younger age, male sex and presence of spinal cord lesion(s) increase the risk of conversion from radiologically isolated syndrome (RIS) to relapsing-remitting multiple sclerosis (RRMS). Elevated cerebrospinal fluid (CSF) chitinase-3-like protein 1 (CHI3L1) levels predict conversion from clinically isolated syndrome (CIS) to RRMS. OBJECTIVE: To evaluate the prognostic value of CSF CHI3L1 in RIS patients for conversion to RRMS. METHODS: We compared CSF CHI3L1 concentrations in RIS, CIS, RRMS and symptomatic controls (SCs). We analysed the influence of epidemiological, radiological and CSF parameters on the risk of clinical event. RESULTS: A total of 211 patients (71 RIS, 48 CIS, 50 RRMS and 42 SC) were included. CSF CHI3L1 levels were lower in RIS than in RRMS and higher in RIS with positive CSF versus negative CSF and SC. The presence of at least one spinal cord lesion was the only independent predictor of faster conversion to RRMS. Association of high CSF CHI3L1 levels, positive CSF (presence of oligoclonal bands and/or an elevated IgG index) or four Barkhof criteria with any spinal cord lesion showed a tendency for reduced mean conversion time. CONCLUSION: CSF CHI3L1 correlates with positive CSF but is not an independent predictor of the risk of conversion from RIS to RRMS.

Age is a critical determinant in recovery from multiple sclerosis relapses.

OBJECTIVE: To evaluate the impact of age on recovery from multiple sclerosis relapses. BACKGROUND: Increasing disability in multiple sclerosis is a consequence of progressive disease and incomplete relapse recovery. METHODS: The first and last-ever relapse data (357 relapses in 193 patients) from the Olmsted County population-based multiple sclerosis cohort were systematically reviewed for age, fulminance, location (optic nerve, brainstem/cerebellar, spinal cord), peak deficit, and maximum recovery. Three different relapse-outcome measures were studied both as paired analyses and as an overall group effect: change from peak deficit to maximum recovery in raw functional system score related to the relapse (ΔFSS), a previously published FSS-based relapse-impact model, and change from peak deficit to maximum recovery in Extended Disability Status Scale (ΔEDSS) score. RESULTS: Older age was linearly associated with worse recovery in the ΔFSS outcome (p = 0.002), ΔEDSS outcome (p < 0.001), and the FSS-based relapse-impact model (p < 0.001). A multivariate analysis of ΔFSS outcome linked poor recovery to older age (p = 0.015), relapse location (transverse myelitis or brainstem/cerebellar syndrome; p < 0.001), and relapse fulminance (p = 0.004). CONCLUSION: Multiple sclerosis-relapse recovery declines in a linear fashion with increased age, which should be considered when making treatment decisions.

Biosimilar infliximab for Behçet's syndrome: a case series.

OBJECTIVES: The efficacy and safety of biosimilar infliximab (bio-IFX) was shown in randomised controlled trials and it was approved for all indications of the reference product in several countries. However, a previous case series of 3 patients with Behçet's syndrome (BS) reported disappointing results. We aimed to share our experience with bio-IFX treatment in different types of organ involvement in patients with BS. METHODS: We reviewed the charts of all BS patients who were prescribed reference infliximab (ref-IFX) or bio-IFX in our BS clinic. Among the 181 BS patients who were prescribed IFX since 2003, 6 (3%) were prescribed bio-IFX due to refractory disease despite conventional immunosuppressives. RESULTS: A total of 6 patients (mean age: 32.1±6.2, mean disease duration: 5.3±1.8 years, 5 men and 1 woman) received bio-IFX for uveitis, nervous system, vascular and joint involvement. Four of the 6 patients obtained remission and stayed in remission during the 16±6.5 months they used bio-IFX. Among the 4 patients who obtained remission, 2 were switched to ref-IFX due to unavailability of bio-IFX infusion set and did not experience adverse events or loss of efficacy. However, relapses occurred during tapering. The other 2 patients are still in remission with bio- IFX. Among the remaining 2 patients, one had to be switched to ref-IFX after the first infusion, due to a change in the reimbursement policy and the other was non-responsive. CONCLUSIONS: Our limited experience showed that bio-IFX may be a safe and effective alternative for patients with BS, refractory to conventional immunosuppressives.

Myelopathy in Behçet's disease: The Bagel Sign.

OBJECTIVE: To describe the clinical and distinctive imaging features of myelopathy associated with Behçet's disease (BD). METHODS: We evaluated the records of patients meeting the following criteria: (1) fulfillment of the International Study Group criteria for BD; (2) clinically suggestive of myelopathy; (3) simultaneous spinal cord and brain magnetic resonance images (MRIs) within 1 month of acute worsening of myelopathy; and (4) follow-up duration ≥ 1 year after initial MRI evaluation. Patients not fulfilling all inclusion criteria and having MRIs with poor quality or missing sequences were excluded. RESULTS: In 11 patients (9 men, 2 women), we studied 14 MRIs during distinct myelopathy episodes and nine follow-up MRIs. Two distinct MRI patterns of spinal cord involvement were described according to T2-weighted (T2W) axial images: (1) "Bagel Sign" pattern: a central lesion with hypointense core and hyperintense rim with or without contrast enhancement; and (2) "Motor Neuron" pattern: a symmetric involvement of the anterior horn cells. Bagel Sign was present in 13 of 14 myelopathy episodes whereas Motor Neuron pattern was observed in 1 of 14 MRIs. Of the 13 MRIs with Bagel Sign long myelopathy (n = 9), both long and short myelopathy (n = 2) and short myelopathy (n = 2) was observed. All patterns cleared with some residual lesions after steroid use and immunomodulation with associated clinical recovery in patients. INTERPRETATION: The signal characteristics of the Bagel Sign potentially represent venous engorgement and/or acute blood products within the spinal cord. To our knowledge, Bagel Sign has not been observed in other forms of longitudinal myelopathy outside of BD, including neuromyelitis optica. Ann Neurol 2017;82:288-298.