Abnormal cervical lymph nodes in multiple sclerosis: a preliminary ultrasound study

Giuliano, Francesca Di; Albanese, Maria; Picchi, Eliseo; Mori, Francesco; Buttari, Fabio; Marfia, Girolama Alessandra; Garaci, Francesco; Mercuri, Nicola Biagio; Floris, Roberto; Centonze, Diego; Marziali, Simone

doi:10.1007/s11547-017-0829-4

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…We did not find any studies in the literature that systematically reported the prevalence of lymphadenopathy in untreated MS as identified by means of FDG-PET or CT scan. We found only one observational study assessing signs of lymphadenopathy in MS patients by means of ultrasound (74). This study found that the size and sonographic morphology of deep cervical lymph nodes in 22 drug-free MS patients is significantly different as compared to 20 healthy donors.…”

Section: Discussionmentioning

confidence: 90%

Differentiating neurosarcoidosis from multiple sclerosis using combined analysis of basic CSF parameters and MRZ reaction

et al. 2023

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BackgroundNeurosarcodosis is one of the most frequent differential diagnoses of multiple sclerosis (MS) and requires central nervous system (CNS) biopsy to establish definite diagnosis according to the latest consensus diagnostic criteria. We here analyzed diagnostic values of basic cerebrospinal fluid (CSF) parameters to distinguish neurosarcoidosis from MS without CNS biopsy.MethodsWe retrospectively assessed clinical, radiological and laboratory data of 27 patients with neurosarcoidosis treated at our center and compared following CSF parameters with those of 138 patients with relapsing-remitting MS: CSF white cell count (WCC), CSF/serum albumin quotient (Qalb), intrathecal production of immunoglobulins including oligoclonal bands (OCB), MRZ reaction, defined as a polyspecific intrathecal production of IgG reactive against ≥2 of 3 the viruses measles (M), rubella (R), and zoster (Z) virus, and CSF lactate levels. Additional inflammatory biomarkers in serum and/or CSF such as neopterin, soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) were assessed.ResultsThere was no significant difference in the frequency of CSF pleocytosis, but a CSF WCC > 30/μl was more frequent in patients with neurosarcoidosis. Compared to MS, patients with neurosarcoidosis showed more frequently an increased Qalb and CSF lactate levels as well as increased serum and CSF levels of sIL-2R, but a lower frequency of intrathecal IgG synthesis and positive MRZ reaction. Positive likelihood ratio (PLR) of single CSF parameters indicating neurosarcoidosis was highest, if (a) CSF WCC was >30/μl (PLR 7.2), (b) Qalb was >10 × 10−3 (PLR 66.4), (c) CSF-specific OCB were absent (PLR 11.5), (d) CSF lactate was elevated (PLR 23.0) or (e) sIL-2R was elevated (PLR>8.0). The combination of (a) one of three following basic CSF parameters, i.e., (a.1.) CSF WCC >30/ul, or (a.2.) QAlb >10 × 10−3, or (a.3.) absence of CSF-specific OCB, and (b) absence of positive MRZ reaction showed the best diagnostic accuracy (sensitivity and specificity each >92%; PLR 12.8 and NLR 0.08).ConclusionCombined evaluation of basic CSF parameters and MRZ reaction is powerful in differentiating neurosarcoidosis from MS, with moderate to severe pleocytosis and QAlb elevation and absence of intrathecal IgG synthesis as useful rule-in parameters and positive MRZ reaction as a rule-out parameter for neurosarcoidosis.

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Section: Discussionmentioning

confidence: 90%

Differentiating neurosarcoidosis from multiple sclerosis using combined analysis of basic CSF parameters and MRZ reaction

et al. 2023

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“…Furthermore, cervical lymph nodes are activated due to cerebral antigens escaping from the permeable BBB after stroke 105 , 106 . Discrepancies between lymph node sizes in treated versus non-treated patients with MS suggests cervical lymph nodes may play a role in MS pathophysiology as well 107 . Not only are these organs notable for their peripheral inflammatory contributions following stroke, but MSC treatments also show SC migration to these organs and subsequent reduction in systemic inflammation 93 , 98 , 99 , 108 .…”

Section: Peripheral Contributionsmentioning

confidence: 99%

Stem Cells Attenuate the Inflammation Crosstalk Between Ischemic Stroke and Multiple Sclerosis: A Review

et al. 2023

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The immense neuroinflammation induced by multiple sclerosis (MS) promotes a favorable environment for ischemic stroke (IS) development, making IS a deadly complication of MS. The overlapping inflammation in MS and IS is a prelude to the vascular pathology, and an inherent cell death mechanism that exacerbates neurovascular unit (NVU) impairment in the disease progression. Despite this consequence, no therapies focus on reducing IS incidence in patients with MS. To this end, the preclinical and clinical evidence we review here argues for cell-based regenerative medicine that will augment the NVU dysfunction and inflammation to ameliorate IS risk.

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“…(9,10) The adaptive immune response against EBV occurs most importantly in the deep cervical lymph nodes (dcLN) (11), which drain CNS lymphatics carrying neuronal autoantigens also in MS patients (12)(13)(14). Interestingly, dcLNs are enlarged in MS patients compared to healthy individuals (15), and clonally expanded B cells extracted from the demyelinating lesions in MS patients commonly derive from the dcLNs (16). Therefore, it is plausible that dcLN could be the original site where MS pathogenesis is initiated.…”

Section: Introductionmentioning

confidence: 99%

Deep cervical lymph nodes of patients with multiple sclerosis show dysregulated B cells in the presence of Epstein-Barr virus

Sarkkinen,

Yohannes,

Kreivi

et al. 2023

Preprint

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Despite the recognized role of Epstein-Barr virus (EBV) in predisposing to multiple sclerosis (MS) and the effectiveness of B cell-depleting therapies in MS, the mechanism of autoimmunity remains elusive. Using fine needle aspirations, we investigated deep cervical lymph nodes (dcLNs), the primary site of the adaptive immune response against EBV, in newly diagnosed untreated MS patients and healthy controls. We characterized the immune landscape of dcLNs with scRNAseq and CITE-seq and observed increased memory B cell proportions and reduced germinal center (GC) B cells with decreased clonality in patients with MS compared to healthy controls. In the patient with an active MS relapse, we detected elevated plasmablasts, reduced GC B cells, and clonally expanded memory CD8 T cells targeting EBV in the dcLN. These findings, along with increased EBV DNA detection in dcLNs and viral loads in patient saliva, support B cell dysregulation as a key mechanism in MS pathogenesis.

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Abnormal cervical lymph nodes in multiple sclerosis: a preliminary ultrasound study

Abstract: The abnormalities shown by ultrasound in cervical lymph nodes are related to deep ones and independent of the ongoing treatment, suggesting a relationship between lymphatic drainage and disease pathology.

Cited by 6 publications

References 26 publications

Differentiating neurosarcoidosis from multiple sclerosis using combined analysis of basic CSF parameters and MRZ reaction

Differentiating neurosarcoidosis from multiple sclerosis using combined analysis of basic CSF parameters and MRZ reaction

Stem Cells Attenuate the Inflammation Crosstalk Between Ischemic Stroke and Multiple Sclerosis: A Review

Deep cervical lymph nodes of patients with multiple sclerosis show dysregulated B cells in the presence of Epstein-Barr virus

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