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Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) represents a T cell‐mediated inflammatory disorder typically characterized by multiple punctate gadolinium enhancement mainly involving the pontine region. Atypical onset with tumefactive infratentorial lesions has been rarely described, representing a significant diagnostic and therapeutic challenge. Case presentation: We describe a 58‐year‐old man who presented in November 2017 with left‐sided hemihypesthesia followed by gait imbalance and diplopia. The first magnetic resonance imaging scans showed an enhancing infratentorial tumefactive lesion empirically treated with intravenous steroids. Extensive laboratory work‐up for the most common causes of tumor‐like lesions was negative, whereas cerebral biopsy disclosed an accumulation of macrophages, perivascular T lymphocytes and rare B cells. Six months later a control magnetic resonance imaging showed multiple punctate hyperintensities in T2‐weighted images peppering the pons and upper cervical spinal cord, which were considered highly suggestive of CLIPPERS. After 3 months of oral prednisone, treatment with rituximab was initiated in April 2019, under which the patient's conditions fully stabilized. Conclusions: Tumor‐like onset was found to be an extremely rare variant of CLIPPERS, which expands the spectrum of possible magnetic resonance imaging manifestation, which can be observed during the course of this disease. The efficacy of rituximab in the treatment of CLIPPERS syndrome supports the role of B cells as important regulators of T‐cell activity. [ABSTRACT FROM AUTHOR]

Background: Alteration of T-follicular helper (TFH) and regulatory (TFR) subpopulations may contribute to the development of auto-reactive B-cell. Objective: To investigate whether changes in TFH and TFR subsets are associated with abnormal IgG synthesis in blood and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. Methods: Paired blood and CSF samples were obtained from 31 untreated relapsing-remitting multiple sclerosis (RRMS) patients at diagnosis. Peripheral blood TFH (CD3+CD4+CXCR5+CD25–CD127+), TFR (CD3+CD4+CXCR5+CD25+CD127dim), conventional T-Helper (TH, CD3+CD4+CXCR5–CD25–CD127+), and regulatory T-cells (T-Reg, CD3+CD4+CXCR5–CD25+CD127dim) were analyzed in all RRMS patients and in 13 healthy controls (HCs). Qualitative and quantitative intrathecal IgG synthesis was evaluated in RRMS patients, who were then further subclassified according to the presence of IgG oligoclonal bands in blood and/or CSF. Results: Compared to HC, RRMS had lower TFR percentage (p < 0.01) and higher TFH/TFR ratio (p < 0.001). In RRMS, TFH/TFR ratio correlated with both qualitative (r = 0.56, p < 0.005) and quantitative intrathecal IgG synthesis (IgG Index: r = 0.78; IgGLoc: r = 0.79; IgGIF: r = 0.76, all p < 0.001). Patients with the highest TFH/TFR ratios had higher percentages of circulating B-cells (36.1 ± 35.2%, p < 0.05). Conclusion: In RRMS, increased TFH/TFR ratio associates with abnormal IgG production in blood and CSF, suggesting that antibody-producing cells, derived from deregulated peripheral germinal center reaction, colonize the CNS. [ABSTRACT FROM AUTHOR]

Combined central and peripheral demyelination (CCPD) is a rare chronic inflammatory disorder of the nervous system. We describe the case of a patient with a history of recurrent myelitis that acutely and simultaneously developed a brain tumour–like lesion and a sensitive-motor demyelinating polyneuropathy. The diagnosis of CCPD was supported by a detailed diagnostic workup. Up to date, no similar cases have been reported in the literature. [ABSTRACT FROM AUTHOR]

Background: The cause and clinical significance of the transient decrease in platelet (PLT) count observed in relapsing remitting multiple sclerosis (RRMS) during alemtuzumab administration remain undefined. The aim of this study was to analyse the kinetics and clinical relevance of early onset thrombocytopaenia in alemtuzumab-treated RRMS. Methods: A total of 26 patients with RRMS were included in a longitudinal study. Blood samples were collected immediately before the first alemtuzumab infusion (D0), and after 3 days (D3), 28 days (D28) and 49 days (D49). PLT, red blood cell (RC), leucocyte and lymphocyte counts, haemoglobin (Hb) concentration and haematocrit (Htc) were measured. Patients with MS were clinically evaluated every day of drug infusion and then at D28 and D49 to verify the presence of signs or symptoms suggestive of thrombocytopaenia. Results: PLT number significantly decreased at D3 (p < 0.005) and was associated with a decrease in RC count (r: 0.53, p < 0.01), Hb (r: 0.42, p = 0.05) and Htc (r: 0.53, p < 0.01). A progressive reversion of PLT number to normal values was observed at D28 and D49. A mild thrombocytopaenia was observed in 12 patients (46.2%), 8 of which (66.6%) had PLT nadir values at D3, and 4 (33.3%) at D28. No sign or symptom suggestive of thrombocytopaenia was observed. A strong correlation between pretreatment and nadir PTL counts (r: 0.59, p < 0.005) was observed; indeed, mild thrombocytopaenia was observed more frequently in these patients with a baseline PTL count lower than 230 X 109/L (83.3% versus 42.9%, p < 0.05). Conclusions: The early PLT decrease in alemtuzumab-treated patients is transient, mild, not associated with clinically relevant events and is probably related to the cytokine-released syndrome. Notwithstanding this, our findings suggest the opportunity for PLT monitoring during infusion and in the following 2 months, since a decrease in PLT count may occur. [ABSTRACT FROM AUTHOR]

Background: The intrathecal production of immunoglobulin (Ig) is a major biological feature of multiple sclerosis (MS), and immunopathological studies have suggested a primary role of the humoral immune response in causing irreversible brain damage.Objective: To evaluate whether, in the early phases of MS, intrathecal Ig synthesis correlates with the presence of cortical lesions (CLs), and if their association could predict the clinical course of the disease.Methods: Eighty-six patients presenting with symptoms and signs suggestive of MS underwent a diagnostic work-up that included magnetic resonance imaging and cerebrospinal fluid examination. The risk ratios (RR) for conversion to MS and for a new disease activity were calculated.Results: Patients with clinically isolated syndromes (CIS) having CLs and intrathecal synthesis of Ig had the highest risk of conversion to MS (RR = 3.4; Wald 95% CI = 1.7–7.0, p < 0.001) whereas CIS patients without CLs and intrathecal synthesis of Ig had the lowest risk of conversion to MS (RR = 0.1, Wald 95% CI = 0.02–0.7, p < 0.001). The highest risk of having disease-related activity during the follow-up was observed in CIS and relapsing–remitting MS patients showing CLs and intrathecal Ig synthesis (RR = 2.1; Wald 95% CI = 1.5–3.1, p < 0.001) while the lowest in CIS and relapsing–remitting MS patients without CLs and intrathecal Ig synthesis (RR = 0.3; Wald 95% CI = 0.1–0.7, p < 0.001).Conclusion: We observed that the association of intrathecal immunoglobulin synthesis and CLs was highly predictive of an earlier CIS conversion to MS as well as of a higher disease activity. [ABSTRACT FROM AUTHOR]

Background: Alteration of T-follicular helper (TFH) and regulatory (TFR) subpopulations may contribute to the development of auto-reactive B-cell., Objective: To investigate whether changes in TFH and TFR subsets are associated with abnormal IgG synthesis in blood and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients., Methods: Paired blood and CSF samples were obtained from 31 untreated relapsing-remitting multiple sclerosis (RRMS) patients at diagnosis. Peripheral blood TFH (CD3+CD4+CXCR5+CD25-CD127+), TFR (CD3+CD4+CXCR5+CD25+CD127 dim ), conventional T-Helper (TH, CD3+CD4+CXCR5-CD25-CD127+), and regulatory T-cells (T-Reg, CD3+CD4+CXCR5-CD25+CD127 dim ) were analyzed in all RRMS patients and in 13 healthy controls (HCs). Qualitative and quantitative intrathecal IgG synthesis was evaluated in RRMS patients, who were then further subclassified according to the presence of IgG oligoclonal bands in blood and/or CSF., Results: Compared to HC, RRMS had lower TFR percentage ( p < 0.01) and higher TFH/TFR ratio ( p < 0.001). In RRMS, TFH/TFR ratio correlated with both qualitative ( r = 0.56, p < 0.005) and quantitative intrathecal IgG synthesis (IgG Index: r = 0.78; IgGLoc: r = 0.79; IgGIF: r = 0.76, all p < 0.001). Patients with the highest TFH/TFR ratios had higher percentages of circulating B-cells (36.1 ± 35.2%, p < 0.05)., Conclusion: In RRMS, increased TFH/TFR ratio associates with abnormal IgG production in blood and CSF, suggesting that antibody-producing cells, derived from deregulated peripheral germinal center reaction, colonize the CNS.

Combined central and peripheral demyelination (CCPD) is a rare chronic inflammatory disorder of the nervous system. We describe the case of a patient with a history of recurrent myelitis that acutely and simultaneously developed a brain tumour-like lesion and a sensitive-motor demyelinating polyneuropathy. The diagnosis of CCPD was supported by a detailed diagnostic workup. Up to date, no similar cases have been reported in the literature.