Mimickers of nervous system involvement among patients with Behçet's syndrome.

OBJECTIVES: We aimed to identify conditions mimicking nervous system involvement among patients with Behçet's syndrome (BS) and to determine clinical, laboratory and imaging findings that may help in the differential diagnosis. METHODS: We screened the charts of 500 consecutive BS patients to identify those who were referred to neurology at any time during their follow-up. The final diagnoses, presenting signs and symptoms, laboratory and imaging results were retrieved from patient charts. Patients who did not have a follow-up visit during the last 3 months were invited to the clinic. RESULTS: Among the 500 BS patients, 116 (23%) had been referred to neurology. Among these, 29 (5.8%) were diagnosed with typical central nervous system involvement of BS (NeuroBS). The type of NeuroBS was parenchymal involvement in 21 patients, cerebral venous sinus thrombosis in 7 patients, and both in 1 patient. 30 patients (6%) had other conditions related to the nervous system, 46 (9.2%) did not have a nervous system disorder, and their symptoms recovered spontaneously, and 11 (2.2%) were lost to follow-up without a definite diagnosis. Of the 30 BS patients who were diagnosed with another nervous system condition, 14 (46%) had primary headache syndromes, 6 (20%) had psychiatric disorders, 2 had entrapment neuropathy, and 1 each had epilepsy, glial tumor, multiple sclerosis, Meniere's disease, optic neuritis, neuroretinitis, steroid myopathy and polyneuropathy. CONCLUSION: Nervous system conditions other than NeuroBS are frequent among BS patients referred to neurology. Caution is required to avoid misdiagnosis of these patients as NeuroBS.

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.

The Effect of Smoking on Inactivated and mRNA Vaccine Responses Applied to Prevent COVID-19 in Multiple Sclerosis.

Introduction: Coronavirus disease 2019 (COVID-19) is the biggest health challenge of recent times. Studies so far reveal that vaccination is the only way to prevent this pandemic. There may be factors that decrease or increase vaccine effectiveness. In multiple sclerosis (MS), some of these factors may cause changes in the effectiveness of the vaccine, depending on the nature of the disease and disease-modifying treatments (DMT). In this study, we aimed to investigate the relationship between antibody titer and smoking in non-treated and DMT-treated MS patients who received inactivated vaccine (Sinovac) and messenger RNA BNT162b2 (BioNTech) mRNA vaccines. Method: Vaccine antibody responses were measured between 4-12 weeks after two doses of inactivated vaccine and mRNA vaccines. Patients were separated into 6 groups as: patients with MS without treatment PwMS w/o T, ocrelizumab, fingolimod, interferons (interferon beta-1a and interferon beta-1b), dimethyl fumarate, and teriflunomide. Antibody titers of smokers and non-smokers were compared for both vaccines and for each group. Results: The study included 798 patients. In the mRNA vaccine group, smokers (n=148; 2982±326 AU/mL) had lower antibody titers compared to the non-smokers (n=244; 5903±545 AU/mL) in total (p=0.020). In the inactivated vaccine group, no significant difference was detected between smokers (n=136; 383±51 AU/mL) and non-smokers (n=270; 388±49 AU/mL) in total (p=0.149). In both vaccine groups, patients receiving ocrelizumab and fingolimod had lower antibody titers than those receiving other DMTs or PwMS w/o T. In untreated MS patients, antibody levels in smokers were lower than in non-smokers in the mRNA vaccine group. No difference was found between antibody levels of smokers and non-smokers in any of the inactivated vaccine groups. Conclusion: Ocrelizumab and fingolimod have lower antibody levels than PwMS w/o T or other DMTs in both mRNA and inactivated vaccine groups. Smoking decreases antibody levels in the mRNA vaccine group, while it has no effect in the inactivated vaccine group.

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.

Coexistence of restless legs syndrome and multiple sclerosis aggravates anxiety and depression / A coexistência da síndrome das pernas inquietas e esclerose múltipla agrava ansiedade e depressão

ABSTRACT Background: Among the comorbidities that accompany multiple sclerosis (MS), restless legs syndrome (RLS) is one of the most common. Anxiety and depression are common psychological comorbidities that impact the quality of life of patients with MS (PwMS), as well as patients with RLS. Objective: To investigate the psychiatric burden of MS and RLS coexistence, we conducted a nationwide, multicenter and cross-sectional survey. Methods: Participants were assessed by using demographic and clinical parameters along with the Hamilton Anxiety and Hamilton Depression Scales (HAM-A and HAM-D). Results: Out of the 1,068 participants, 173 (16.2%) were found to have RLS [RLS(+)] and 895 (83.8%) did not [RLS(-)]. The mean scores for HAM-A and HAM-D were significantly higher among RLS(+) subjects than among RLS(-) subjects (p<0.001 for all variables). Conclusions: According to our data, the presence of RLS in PwMS may increase the occurrence of both anxiety and depression symptoms. Awareness and treatment of RLS in PwMS could possibly reduce the symptoms of psychiatric comorbidities originating from RLS.

RESUMO Antecedentes: Considerando-se as comorbidades que acompanham a esclerose múltipla (EM), a síndrome das pernas inquietas (SPI) é uma das mais comuns, e ansiedade e depressão são comorbidades psicológicas comuns que afetam a qualidade de vida de pacientes com EM, bem como de pacientes com SPI. Objetivo: Investigar a carga psiquiátrica da coexistência de EM e SPI por meio de uma pesquisa nacional, multicêntrica e transversal. Métodos: Os participantes foram avaliados por parâmetros demográficos e clínicos, além da versão turca das escalas de ansiedade e depressão de Hamilton (HAM-A e HAM-D). Resultados: Dos 1.068 participantes, 173 (16,2%) apresentaram SPI [SPI (+)] e 895 (83,8%) não [SPI (-)]. As pontuações médias no HAM-A e no HAM-D foram significativamente maiores em indivíduos com SPI (+) do que naqueles com SPI (-) (p <0,001 para todas as variáveis). Conclusões: De acordo com nossos dados, a presença de SPI na EM pode aumentar a ocorrência de sintomas de ansiedade e depressão. A conscientização e o tratamento da SPI na EM podem reduzir os sintomas de comorbidades psiquiátricas originadas da SPI.

Risk Factors and Time to Clinical Symptoms of Multiple Sclerosis Among Patients With Radiologically Isolated Syndrome.

Importance: Younger age, oligoclonal bands, and infratentorial and spinal cord lesions are factors associated with an increased 10-year risk of clinical conversion from radiologically isolated syndrome (RIS) to multiple sclerosis (MS). Whether disease-modifying therapy is beneficial for individuals with RIS is currently unknown. Objectives: To evaluate the 2-year risk of a clinical event (onset of clinical symptoms of MS) prospectively, identify factors associated with developing an early clinical event, and simulate the sample size needed for a phase III clinical trial of individuals with RIS meeting 2009 RIS criteria. Design, Setting, and Participants: This cohort study used data on prospectively followed-up individuals with RIS identified at 1 of 26 tertiary centers for MS care in France that collect data for the Observatoire Français de la Sclérose en Plaques database. Participants were aged 10 to 80 years with 2 or more magnetic resonance imaging (MRI) scans after study entry and an index scan after 2000. All diagnoses were validated by an expert group, whose review included a double centralized MRI reading. Data were analyzed from July 2020 to January 2021. Exposure: Diagnosis of RIS. Main Outcomes and Measures: Risk of clinical event and associated covariates at index scan were analyzed among all individuals with RIS. Time to the first clinical event was compared by covariates, and sample size estimates were modeled based on identified risk factors. Results: Among 372 individuals with RIS (mean [SD] age at index MRI scan, 38.6 [12.1] years), 354 individuals were included in the analysis (264 [74.6%] women). A clinical event was identified among 49 patients (13.8%) within 2 years, which was associated with an estimated risk of conversion of 19.2% (95% CI, 14.1%-24.0%). In multivariate analysis, age younger than 37 years (hazard ratio [HR], 4.04 [95% CI, 2.00-8.15]; P < .001), spinal cord lesions (HR, 5.11 [95% CI, 1.99-13.13]; P = .001), and gadolinium-enhancing lesions on index scan (HR, 2.09 [95% CI, 1.13-3.87]; P = .02) were independently associated with an increased risk of conversion to MS. Having 2 factors at the time of the index MRI scan was associated with a risk of 27.9% (95% CI, 13.5%-39.9%) of a seminal event within 2 years, increasing to 90.9% (95% CI, 41.1%-98.6%) for individuals with all 3 factors (3 risk factors vs none: HR, 23.34 [95% CI, 9.08-59.96]; P < .001). Overall, with 80% power to detect an effect size of 60% within 24 months, a total of 160 individuals with RIS were needed assuming an event rate of 20%. Conclusions and Relevance: This study found that age younger than age 37 years, spinal cord involvement, and gadolinium-enhancing lesions on index MRI scan were associated with earlier clinical disease and relevant to the number of enrolled patients needed to detect a potential treatment effect.

Co-existence of multiple sclerosis and anti-NMDA receptor encephalitis: A case report and review of literature.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a serious autoimmune disorder characterized by psychiatric symptoms, seizures and movement disorder. Predisposing factors have been reported since the time it was described, and its pathophysiology has been tried to be clarified over the years. Although overlap with other demyelinating diseases had been reported, such an association between Multiple Sclerosis (MS) anti ANTI-NMDAR encephalitis is limited to only a few case reports. In this article, a patient diagnosed with relapsing remitting multiple sclerosis (RRMS) for ten years who then developed NMDA-R encephalitis while on disease modifying treatment will be presented and possible common pathophysiology with previously reported literature will be discussed.

2018 update of the EULAR recommendations for the management of Behçet's syndrome.

Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.

Next generation sequencing analysis of patients with familial cervical artery dissection.

BACKGROUND: The cause of cervical artery dissection is not well understood. We test the hypothesis that mutations in genes associated with known arterial connective tissue disorders are enriched in patients with familial cervical artery dissection. PATIENTS AND METHODS: Patient duos from nine pedigrees with familial cervical artery dissection were analyzed by whole exome sequencing. Single nucleotide variants in a panel of 11 candidate genes (ACTA2, MYH11, FBN1, TGFBR1, TGFBR2, TGFB2, COL3A1, COL4A1, SMAD3, MYLK and SLC2A10) were prioritized according to functionality (stop-loss, nonsense, and missense variants with polyphen-2 score ≥0.95). Variants classified as "benign" or "likely benign" in the ClinVar database were excluded from further analysis. For comparison, non-benign stop-loss, nonsense and missense variants with polyphen-2 score ≥0.95 in the same panel of candidate genes were identified in the European non-Finnish population of the ExAC database (n = 33,370). RESULTS: Non-benign Single nucleotide variants in both affected patients were identified in four of the nine cervical artery dissection families (COL3A1; Gly324Ser, FBN1: Arg2554Trp, COL4A1: Pro116Leu, and TGFBR2: Ala292Thr) yielding an allele frequency of 22.2% (4/18). In the comparison group, 1782 variants were present in 33,370 subjects from the ExAC database (allele frequency: 1782/66,740 = 2.7%; p = 0.0008; odds ratio = 14.2; 95% confidence interval = 3.8-52.9). CONCLUSION: Cervical artery dissection families showed enrichment for non-benign variants in genes associated with arterial connective tissue disorders. The observation that findings differed across families indicates genetic heterogeneity of familial cervical artery dissection.

Infliximab is a plausible alternative for neurologic complications of Behçet disease.

OBJECTIVE: We evaluated the effectiveness of infliximab in patients with neuro-Behçet syndrome for whom other immunosuppressive medications had failed. METHODS: Patients whose common immunosuppressive medications fail in recurrent neuro-Behçet syndrome need an alternative. We report our experience with the tumor necrosis factor α blocker infliximab for long-term treatment of neuro-Behçet syndrome. We recruited patients within a multidisciplinary referral practice of Behçet disease and prospectively followed everyone with a neurologic symptom(s). Patients (n = 16) with ≥2 neurologic bouts (excluding purely progressive disease) while on another immunosuppressive treatment were switched to and successfully sustained on infliximab (5 mg/kg in weeks 0, 2, and 6, then once every 8 weeks; minimum follow-up duration ≥12 months). Infliximab was stopped within 2 months after initiation in one patient because of pulmonary and CNS tuberculosis. RESULTS: Patients had stepwise worsening due to relapses in the Expanded Disability Status Scale modified for neuro-Behçet syndrome before switching to infliximab (median score of 5.0, range 2.0-7.0; median neuro-Behçet syndrome duration 29.1 months, range 5.0-180.7). Median duration of preinfliximab immunosuppressive medication use was 20.0 months (range 3.0-180.7). In all 15 patients, during infliximab treatment (median score 4.0, range 2.0-7.0; median duration 39.0 months, range 16.0-104.9 months), neurologic relapses were completely aborted and there was no further disability accumulation. CONCLUSION: We observed a significant beneficial effect of infliximab in neuro-Behçet syndrome. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with neuro-Behçet syndrome whose other immunosuppressive medications failed, infliximab prevents further relapses and stabilizes disability.

Recurrent longitudinal extensive transverse myelitis in a neuro-Behçet syndrome treated with infliximab.

BACKGROUND: Spinal cord involvement is not common, but can be seen in neuro-Behçet's syndrome (NBS). The major site of involvement is the cervical spinal cord with the myelitis-like inflammatory lesions continuing more than two segments, and extending to the brainstem. CASE: A 30-year-old male patient who has been followed with a diagnosis of Behçet's syndrome admitted to our neurology department clinically and radiologically suggestive of recurrent and extensive longitudinal myelitis. His anti-aquaporine antibody was negative. Because of insufficient effect of azathioprine, cyclophosphamide, and corticosteroids, infliximab was started. His clinical and radiological status is stationary for 3 years under infliximab treatment. DISCUSSION: Myelitis such as that occurring in our patient may have a similar presentation like neuromyelitis optica (NMO), which should therefore be included in differential diagnosis. Myelitis observed in both NMO and NBS shows spinal cord lesions longer than three or more vertebrae. Anti-aquaporine antibody must be evaluated in all patients presenting with longitudinal myelitis. Anti-tumor necrosis factor agent infliximab might be an alternative treatment in severe form of NBS such as myelitis. CONCLUSION: In our case, successful treatment of recurrent and extensive longitudinal transverse myelitis in NBS with infliximab was demonstrated.

Neuro-Behçet disease and autoinflammatory disorders.

Misregulation of innate immunity leads to autoinflammation. Behçet disease is an autoinflammatory condition involving recurrent attacks of inflammation in skin, eyes, joints, and even the nervous system. The etiology may involve vascular inflammation. Central nervous system involvement in neuro-Behçet disease (NBD) comes in the form of parenchymal NBD or nonparenchymal NBD. The parenchymal form has a predilection for the brainstem, diencephalon and cerebral hemispheres, and represents a meningoencephalitis thought to be related to small vessel vasculitis. Cerebral venous sinus thrombosis, arising from a vasculitic process of large veins, comprises the majority of vascular NBD cases. The rarer monogenetic autoinflammatory syndromes are characterized by periodic fever, and typically present in the pediatric population. Neurologic involvement in these syndromes typically presents in the form of an aseptic meningitis. Treatment of autoinflammatory disorders involves immune modulation with corticosteroids, disease-modifying antirheumatic medications, and increasingly antibodies targeting cytokines like tumor necrosis factor α and interleukin 1.

Anti-JC virus antibody prevalence in a multinational multiple sclerosis cohort.

JC virus (JCV) is an opportunistic virus known to cause progressive multifocal leukoencephalopathy. Anti-JC virus (Anti-JCV) antibody prevalence in a large, geographically diverse, multi-national multiple sclerosis (MS) cohort was compared in a cross-sectional study. Overall, anti-JCV antibody prevalence was 57.6%. Anti-JCV antibody prevalence in MS patients ranged from approximately 47% to 68% across these countries: Norway, 47.4%; Denmark, 52.6%; Israel, 56.6%; France, 57.6%; Italy, 58.3%; Sweden, 59.0%; Germany, 59.1%; Austria, 66.7% and Turkey, 67.7%. Prevalence increased with age (from 49.5% in patients < 30 years of age to 66.5% in patients ≥ 60 years of age; p < 0.0001 comparing all age categories), was lower in females than in males (55.8% versus 61.9%; p < 0.0001) and was not affected by prior immunosuppressant or natalizumab use.

Voiding dysfunction due to multiple sclerosis: a large scale retrospective analysis

PURPOSE: To assess the outcome of urologic evaluation in patients with voiding dysfunction due to multiple sclerosis (MS) and to determine the relationship between urological and neurological parameters of these patients. MATERIAL AND METHODS: We retrospectively reviewed the medical records of 249 consecutive patients (162 female and 87 male) with MS who were referred to our clinic between 1991 and 2006, with a median time of 4 years (range 3 months to 26 years) of MS onset. Data was analyzed with respect to patient demographics and findings of initial evaluation. Lower urinary tract symptoms were evaluated by Boyarsky symptom index. RESULTS: All patients except 13 had lower urinary tract symptoms and 70 percent manifested mixed symptoms. Total, storage and voiding symptom scores correlated with expanded disability status scale scores (p < 0.05). Twelve patients (5 percent) had abnormal upper urinary tract. Ultrasound findings of lower urinary tract were abnormal in 12 patients (5 percent). No demographic parameters were associated with abnormal findings of upper urinary tract on univariate analysis. Urodynamic evaluation of 75 patients (30.1 percent) revealed detrusor overactivity with or without detrusor-sphincter dyssynergia in 56 (75 percent). No correlation was found between urodynamic diagnosis and upper tract deterioration and urinary symptom scores (p > 0.05). CONCLUSIONS: The prevalence of mixed symptoms in patients with MS is higher than storage or voiding symptoms alone. Although detrusor overactivity and detrusor-sphincter dyssynergia were the most common urodynamic diagnoses, upper urinary tract deterioration was rare in our series.

The validation of ID Migraine screener in neurology outpatient clinics in Turkey.

The aim of this study was to investigate the validity of the ID Migraine test in neurology outpatient clinics (NOCs), regardless of their presenting complaints. Patients admitted to 41 NOCs were screened. Eligible subjects (n=3682) were evaluated by a neurologist for headache diagnosis according to the International Headache Society criteria and asked the 3-item screening questions of the ID Migraine test. Of 3682 patients, 917 (24.9%) were diagnosed as migraine, whereas 1171 (31.8%) were ID Migraine test positive. The sensitivity of the ID Migraine test for neurologist's diagnosis of migraine was 91.8%, specificity was 63.4%, positive predictive value was 71.9% and negative predictive value was 88.4%. The ID Migraine test is easy to use and a practical test that could alert the neurologist to diagnose patients having other complaints. This test would help to increase the diagnosis and treatment rate of undiagnosed migraine patients in NOCs.