Polyspecific, antiviral immune response distinguishes multiple sclerosis and neuromyelitis optica

Background: A polyspecific, intrathecal humoral immune response against neurotropic viruses such as measles, rubella and varicella zoster virus (MRZ reaction, MRZR) is present in 80--100% of patients with multiple sclerosis (MS), but has not to date been evaluated in patients with neuromyelitis optica (NMO).Aims: To evaluate whether MRZR distinguishes NMO and MS.Methods: 20 patients with NMO and 42 with MS were included. The intrathecal synthesis of antibodies against measles, rubella and varicella zoster virus was detected by calculation of the respective antibody indices (AI).Results: A positive MRZ reaction, as defined by a combination of at least two positive AIs, was found in 37/42 MS, but in only 1/20 NMO patients (p<0.0001). Median AI values differed significantly between the groups (p<0.0005).Conclusions: The polyspecific antiviral humoral immune response characteristic for MS is widely missing in NMO, irrespective of the NMO-IgG status of the patients. Our findings further strengthen the case for NMO being pathologically distinct from MS

MOG encephalomyelitis: international recommendations on diagnosis and antibody testing

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM (“red flags”) that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation

Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

Tocilizumab in MOG-antibody spectrum disorder: a case report

Background: Myelin oligodendrocyte glycoprotein antibody-related spectrum disorders (MOG-SD) are a heterogeneous group of inflammatory demyelinating diseases of the central nervous system, usually responsive to conventional immunosuppressive therapies. However, knowledge about treatment of non-responder patients is scarce. Methods: We report on a 20-year-old MOG-SD patient who experienced clinical deterioration despite rituximab-induced B-cell depletion. Results: Rescue therapy with tocilizumab (TCZ) prevented further relapses, with reduction of spinal-cord load on MRI, and a remarkable reduction of disability at the two-year follow-up. Conclusion: Our observations suggest that TCZ could induce clinico-radiologic improvements, which make it as an option for the treatment of MOG-SD

Human Polyomaviruses in the Cerebrospinal Fluid of Neurological Patients.

BACKGROUND: Central nervous system (CNS) infections by human polyomaviruses (HPyVs), with the exception of JC (JCPyV), have been poorly studied. METHODS: In total, 234 cerebrospinal fluid (CSF) samples were collected from patients affected with neurological disorders. DNA was isolated and subjected to quantitative real-time PCR (Q-PCR) for the detection of six HPyVs: JCPyV, BKPyV, Merkel cell PyV (MCPyV), HPyV6, HPyV7, and HPyV9. Where possible, the molecular characterization of the viral strains was carried out by nested PCR and automated sequencing. RESULTS: JCPyV was detected in 3/234 (1.3%), BKPyV in 15/234 (6.4%), MCPyV in 22/234 (9.4%), and HPyV6 in 1/234 (0.4%) CSF samples. JCPyV was detected at the highest (p < 0.05) mean load (3.7 7 107 copies/mL), followed by BKPyV (1.9 7 106 copies/mL), MCPyV (1.9 7 105 copies/mL), and HPyV6 (3.3 7 104 copies/mL). The noncoding control regions (NCCRs) of the sequenced viral strains were rearranged. CONCLUSIONS: HPyVs other than JCPyV were found in the CSF of patients affected with different neurological diseases, probably as bystanders, rather than etiological agents of the disease. However, the fact that they can be latent in the CNS should be considered, especially in immunosuppressed patients

Early red nucleus atrophy in relapse-onset multiple sclerosis

No study has investigated red nucleus (RN) atrophy in multiple sclerosis (MS) despite cerebellum and its connections are elective sites of MS-related pathology. In this study, we explore RN atrophy in early MS phases and its association with cerebellar damage (focal lesions and atrophy) and physical disability. Thirty-seven relapse-onset MS (RMS) patients having mean age of 35.6 ± 8.5 (18–56) years and mean disease duration of 1.1 ± 1.5 (0–5) years, and 36 age- and sex-matched healthy controls (HC) were studied. Cerebellar and RN lesions and volumes were analyzed on 3 T-MRI images. RMS did not differ from HC in cerebellar lobe volumes but significantly differed in both right (107.84 ± 13.95 mm3 vs. 99.37 ± 11.53 mm3, p =.019) and left (109.71 ± 14.94 mm3 vs. 100.47 ± 15.78 mm3, p =.020) RN volumes. Cerebellar white matter lesion volume (WMLV) inversely correlated with both right and left RN volumes (r = −.333, p =.004 and r = −.298, p =.010, respectively), while no correlation was detected between RN volumes and mean cortical thickness, cerebellar gray matter lesion volume, and supratentorial WMLV (right RN: r = −.147, p =.216; left RN: r = −.153, p =.196). Right, but not left, RN volume inversely correlated with midbrain WMLV (r = −.310, p =.008), while no correlation was observed between whole brainstem WMLV and either RN volumes (right RN: r = −.164, p =.164; left RN: r = −.64, p =.588). Finally, left RN volume correlated with vermis VIIb (r =.297, p =.011) and right interposed nucleus (r =.249, p =.034) volumes. We observed RN atrophy in early RMS, likely resulting from anterograde axonal degeneration starting in cerebellar and midbrain WML. RN atrophy seems a promising marker of neurodegeneration and/or cerebellar damage in RMS